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Information on EC 2.7.11.2 - [pyruvate dehydrogenase (acetyl-transferring)] kinase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the pyruvate dehydrogenase complex in mammals. Phosphorylation inactivates EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring).
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This record set is specific for:
Homo sapiens
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Word Map
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
pyruvate dehydrogenase kinase, pyruvate dehydrogenase kinase 4, pdh kinase, pdhk2, pdhk1, pdk-4, pyruvate dehydrogenase kinase-4, pdhk4, pyruvate dehydrogenase kinase 2, pdk-2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
kinase (phosphorylating), pyruvate dehydrogenase
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PDH kinase
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PDK-2
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PDK-4
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PDKI
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pyruvate dehydrogenase kinase
pyruvate dehydrogenase kinase (phosphorylating)
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pyruvate dehydrogenase kinase 1
pyruvate dehydrogenase kinase 2
pyruvate dehydrogenase kinase 3
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pyruvate dehydrogenase kinase 4
pyruvate dehydrogenase kinase activator protein
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pyruvate dehydrogenase kinase I
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pyruvate dehydrogenase kinase-3
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pyruvate dehydrogenase kinase-4
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additional information
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PDK isozymes and the related branched-chain dehydrogenase kinase form a unique family of serine kinases
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)]phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phopho group transfer
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phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:[pyruvate dehydrogenase (acetyl-transferring)] phosphotransferase
The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the pyruvate dehydrogenase complex in mammals. Phosphorylation inactivates EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring).
CAS REGISTRY NUMBER
COMMENTARY hide
9074-01-5
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
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phosphorylation of serine residues of the E1 PDC component
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ir
ATP + Ac-YHGHSMSDPGVSYR
ADP + [Ac-YHGHSMSDPGVSYR]phosphate
show the reaction diagram
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?
ATP + PDHA1
ADP + phosphorylated PDHA1
show the reaction diagram
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-
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?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
ATP + SMAD1/5/8 protein
?
show the reaction diagram
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-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
ATP + [pyruvate dehydrogenase A1 (acetyl-transferring)]
ADP + [pyruvate dehydrogenase A1 (acetyl-transferring)] phosphate
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
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?
ATP + SMAD1/5/8 protein
?
show the reaction diagram
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-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
ATP + [pyruvate dehydrogenase A1 (acetyl-transferring)]
ADP + [pyruvate dehydrogenase A1 (acetyl-transferring)] phosphate
show the reaction diagram
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATPgammaS
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dissociation constants as ATP in binding to PDK3
additional information
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no activity with GTP
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Na+
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hinders interaction between PDK2 and the inner lipoyl domain L2
phosphate
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activates
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S)-2,6-diamino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)hexan-1-one
-
(2S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxypropan-1-one
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(2S,3S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxybutan-1-one
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(3R)-3-amino-4-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-4-oxobutanamide
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(3S)-3-amino-4-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]azetidin-1-yl)-4-oxobutanamide
-
(3S)-3-amino-4-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-4-oxobutanamide
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(3S)-3-amino-4-[(3R)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
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(3S)-3-amino-4-[(3S)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
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(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]-1,4-diazepan-1-yl]-4-oxobutanamide
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(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl]-4-oxobutanamide
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(4-benzylpiperidin-1-yl)[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazol-3-yl]methanone
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(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)[(3R,5R)-3,4,5-trihydroxycyclohexyl]methanone
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(4S)-4-amino-5-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-5-oxopentanamide
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
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(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-phenylpiperazin-1-yl)prop-2-en-1-one
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(R)-4-(3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenylsulfonyl)-N,N-dimethylbenzamide
AZD7545
-
2-(2,6-dimethylphenoxy)-N-(1,3-dioxo-2-phenyl-2,3-dihydro-1H-isoindol-4-yl)acetamide
45.56% inhibition at 0.01 mM
2-(4-nitrophenyl)-2-oxoethyl 1H-indol-3-ylacetate
41.16% inhibition at 0.01 mM
2-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidine-1-carbonyl)benzoic acid
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2-(5,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-nitrobenzoic acid
79.34% inhibition at 0.01 mM
2-([4-oxo-6-[(4-phenylpiperazin-1-yl)methyl]-4H-pyran-3-yl]oxy)-N-(propan-2-yl)acetamide
64.3% inhibition at 0.01 mM
2-chloro-4-formyl-6-methoxyphenyl 4-chloro-3-nitrobenzoate
41.26% inhibition at 0.01 mM
2-methyl-3-(2-[4-[4-(trifluoromethyl)benzoyl]piperazin-1-yl]ethoxy)-4H-pyran-4-one
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2-methyl-3-[2-oxo-2-(4-phenylpiperazin-1-yl)ethoxy]-4H-pyran-4-one
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2-methyl-3-[2-oxo-2-[4-(pyridin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
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2-methyl-3-[2-oxo-2-[4-(pyrimidin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
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2-methyl-3-[2-[4-(2-methylphenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
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2-methyl-3-[2-[4-(2-nitrobenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
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2-methyl-3-[2-[4-(2-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
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2-methyl-3-[2-[4-(3-methylbenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
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2-methyl-3-[2-[4-(4-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
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2-methyl-3-[2-[4-(pyridin-2-ylcarbonyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
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2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro-1H-isoindole-4,5-diol
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2-[(6-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]-4-oxo-4H-pyran-3-yl)oxy]-N-(propan-2-yl)acetamide
79.7% inhibition at 0.01 mM
2-[(6-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-4-oxo-4H-pyran-3-yl)oxy]-N-cyclopentylacetamide
47.5% inhibition at 0.01 mM
2-[5-[(2S)-1-benzylpiperidin-2-yl]-3-(oxan-4-yl)-1H-1,2,4-triazol-1-yl]ethan-1-ol
93.7% inhibition at 0.01 mM
3-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-oxopropanoic acid
-
3-[2-(4-(3-chlorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
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3-[2-(4-(3-fluorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
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3-[2-(4-benzoylpiperazin-1-yl)ethoxy]-2-methyl-4H-pyran-4-one
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3-[2-[4-(2-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
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3-[2-[4-(2-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
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3-[2-[4-(3,5-dimethoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
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3-[2-[4-(3,5-dimethylphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
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3-[2-[4-(3-methoxybenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(3-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(4-chlorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(4-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(dichloroacetyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(diphenylmethyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
-
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3-[2-[4-(furan-2-ylcarbonyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
-
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4,5-dichloro-2-[[(2,4-dichlorophenyl)amino]carbonyl]benzoic acid
36.08% inhibition at 0.01 mM
4-(5-[[1-(2,3-dihydroxypropyl)piperidin-4-yl]amino]-1,3-dihydro-2H-isoindole-2-sulfonyl)benzene-1,3-diol
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4-([(2R,5S)-2,5-dimethyl-4-[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]piperazin-1-yl]carbonyl)benzonitrile
-
4-chloro-2-[[4-(propionyloxy)benzoyl]amino]enzoic acid
39.88% inhibition at 0.01 mM
4-[(5-amino-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
-
4-[(5-hydroxy-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
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4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
inhibitor M77976 binds to the ATP-binding pocket of PDK4 and causes local conformational changes with complete disordering of the ATP lid. M77976 binding also leads to a large domain rearrangement that further expands the active-site cleft of PDK4 compared with the ADP- and AMPPNP-bound forms
4-[5-(cyclohexylamino)-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
-
4-[5-[(1-benzylpiperidin-4-yl)amino]-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
-
4-[[(3S)-3-(2-hydroxyethyl)-4-(3-methylbut-2-en-1-yl)piperazin-1-yl]methyl]-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
86.4% inhibition at 0.01 mM
4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]-N-ethylpiperidine-1-carboxamide
-
4-[[5-(piperazin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
-
4-[[5-(piperidin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
-
4-[[5-(piperidin-4-ylamino)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
-
5-(3-bromophenyl)-4-(2-furoyl)-3-hydroxy-1-(5-isopropyl-1,3,4-thiadiazol-2-yl)-1,5-dihydro-2H-pyrrol-2-one
37.15% inhibition at 0.01 mM
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-(pyridin-4-yl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-(2-methylpropyl)piperidin-4-yl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(pyridin-4-yl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-[(morpholin-4-yl)methyl]phenyl]-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[(2,4-dichlorophenyl)methyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-(cyclopropylmethyl)piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-[4-(dimethylamino)phenyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
5-bromo-2-([3-[(3-methylbenzoyl)amino]benzoyl]amino)benzoic acid
73.53% inhibition at 0.01 mM
5-[(1,3-benzodioxol-5-yloxy)methyl]-N-(imidazo[1,2-a]pyridin-3-ylmethyl)-N-methyl-1H-pyrazole-3-carboxamide
95.6% inhibition at 0.01 mM
6-(3,5-dichloro-4-hydroxybenzylidene)-5-imino-2-[(2-phenoxyethyl)thio]-5,6-dihydro-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one
42.87% inhibition at 0.01 mM
6-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-6-oxohexanoic acid
-
6-bromo-2-(2-methoxyphenyl)-4H-3,1-benzoxazin-4-one
45.07% inhibition at 0.01 mM
9-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-9-oxononanoic acid
-
adenosine 5'-[beta,gamma-imido]triphosphate
-
-
AZ12
-
i.e. N-[4-([ethylanilino]sulfonyl)2-methylphenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, binding structure, requires K+ for inhibition
AZD7545
compound K
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
Dichloroacetate
dichloroacetophenone
-
dihydrolipoic acid
-
inhibits the activity of PDK3 towards the reconstituted PD complex slightly, but the activity towards E1 alone completely, inhibition mechanism
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
49.53% inhibition at 0.01 mM
Insulin
-
decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma
-
methyl 4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]piperidine-1-sulfinate
-
N-(1-acetylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
N-(1-benzylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
N-(3-methoxyphenyl)-2-[(phenylsulfonyl)amino]-5-pyrimidinecarboxamide
65.66% inhibition at 0.01 mM
N-(4-(2-chloro-5-methylpyrimidin-4-yl)-phenyl)-N-(4-((2,2-difluoroacetamido)methyl)benzyl)-2,4-dihydroxybenzamide
Ver-246608
-
N-butyl-3-(2-hydroxyphenyl)-N-(pyridin-4-ylmethyl)-1H-pyrazole-5-carboxamide
89.6% inhibition at 0.01 mM
N-methyl-2-([4-oxo-6-[(4-phenylpiperazin-1-yl)methyl]-4H-pyran-3-yl]oxy)acetamide
54.1% inhibition at 0.01 mM
N-[2-([[4-methyl-6-(piperidin-1-yl)pyrimidin-2-yl]methyl]amino)-2-oxoethyl]benzamide
20.1% inhibition at 0.01 mM
N1-(2-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]ethyl)-L-aspartamide
-
N1-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]propyl)-L-aspartamide
-
Nov3r
P53
-
negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2
Pfz3
-
i.e. N-(2-aminoethyl)-2-(3-chloro-4-[(4-isopropylbenzyl)oxy]phenyl)acetamide, binding site structure, involves e.g. the R domain, allosteric inhibition mechanism, overview
PS10
2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro-1H-isoindole-4,6-diol
-
pyruvate
R-lipoic acid
-
inhibits isozyme PDK3 activity in the reconstituted PD complex, but not towards E1 alone, inhibition mechanism
radicicol
Rapamycin
-
inhibits PDK2 and PDK4, has no effect on insulin-caused downregulation of the isozymes
S-lipoic acid
-
inhibits isozyme PDK3 activity in the reconstituted PD complex, but not towards E1 alone, inhibition mechanism
thiamine diphosphate
-
-
VER-246608
-
-
ZINC01073908
-
-
ZINC08764476
-
-
ZINC08792096
-
-
ZINC08876663
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-CoA
AZD7545
structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview, when the E2p/E3BP core is absent, AZD7545 stimulates scaffold-free basal PDK1 and PDK3 activities to 1.3fold and 10fold, respectively
dihydrolipoyl transacetylase
-
glucocorticoids
-
regulate the basal expression level of PDK4, bind to a glucorticoid response element GRE located in the proximal promotor requiring binding of FOXO proteins, FOXO protein binding to the GRE can be inhibited by insulin, glucocorticoids act synergistically with retinoic acid
-
inner lipoyl-bearing domain 2
-
i.e. L2, binding to the inner lipoyl domain L2 of E2 component of the PDC enzyme complex activates and regulates the enzyme by conformational changes and disrupting the ATP lid and eliminating product inhibition by ADP, mechanism, L2 binding strongly decreases PDHK2 affinity for ATP, strongest activation occurrs in presence of E1, E1-binding domain, and E2, overview
-
L2 domain
-
inner lipoyl domain of the E2 component of PDC, activates PDK2
-
L2 domain of pyruvate dehydrogenase complex
-
binding to the inner lipoyl domains L2 of E2 component activate the enzyme by conformational changes and disrupting the ATP lid and eliminating product inhibition by ADP, binding structure, overview, L2 binding increases affinities for both ADP and ATP
-
lipoyl domain L2
-
L2 of the PDK3-containing pyruvate dehydrogenase complex induces a cross-tail conformation in PDK3, resulting in an opening of the active site cleft and the stimulation of kinase activity
-
oleate
-
activates PDK2 and PDK4 nearly 2fold at 0.1 mM, not synergistic with palmitate, stimulation is completely inhibited by insulin at 0.001 mM
palmitate
-
activates PDK2 and PDK4 nearly 2fold at 0.1 mM, not synergistic with oleate, stimulation is completely inhibited by insulin at 0.001 mmM
phosphate
-
isozyme PDK43, direct inhibition and elevation of the Km for ATP
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.006 - 1.16
ATP
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12 - 4.7
ATP
0.0014 - 0.0032
pyruvate dehydrogenase
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0031
adenosine 5'-[beta,gamma-imido]triphosphate
-
pH 7.4, 30°C, versus ATP
0.14 - 0.52
ADP
-
pH 7.4, 30°C, versus ATP, dependent on the assay conditions concerning buffer composition, overview
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00058
(2S)-2,6-diamino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)hexan-1-one
Homo sapiens
at pH 7.5 and 25°C
0.000068
(2S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxypropan-1-one
Homo sapiens
at pH 7.5 and 25°C
0.000091
(2S,3S)-2-amino-1-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-hydroxybutan-1-one
Homo sapiens
at pH 7.5 and 25°C
0.000065
(3S)-3-amino-4-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]azetidin-1-yl)-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000058
(3S)-3-amino-4-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000221
(3S)-3-amino-4-[(3R)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000156
(3S)-3-amino-4-[(3S)-3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]pyrrolidin-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.001514
(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]-1,4-diazepan-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.000767
(3S)-3-amino-4-[4-[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl]-4-oxobutanamide
Homo sapiens
at pH 7.5 and 25°C
0.01
(4-benzylpiperidin-1-yl)[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazol-3-yl]methanone
Homo sapiens
IC50 above 0.01 mM, pH and temperature not specified in the publication
0.000432
(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)[(3R,5R)-3,4,5-trihydroxycyclohexyl]methanone
Homo sapiens
at pH 7.5 and 25°C
0.000072
(4S)-4-amino-5-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-5-oxopentanamide
Homo sapiens
at pH 7.5 and 25°C
0.000604
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.001417
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.002949
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000776
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000952
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000878
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000521
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000845
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(2-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.004306
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3,4-dichlorophenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.002369
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000491
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(3-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000557
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(4-methoxyphenyl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.00105
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.00107
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.001916
(E)-3-(5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-isoxazol-3-yl)-1-(4-phenylpiperazin-1-yl)prop-2-en-1-one
Homo sapiens
pH and temperature not specified in the publication
0.000565
2-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidine-1-carbonyl)benzoic acid
Homo sapiens
at pH 7.5 and 25°C
0.0051
2-methyl-3-(2-[4-[4-(trifluoromethyl)benzoyl]piperazin-1-yl]ethoxy)-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0018
2-methyl-3-[2-oxo-2-(4-phenylpiperazin-1-yl)ethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
2-methyl-3-[2-oxo-2-[4-(pyridin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
2-methyl-3-[2-oxo-2-[4-(pyrimidin-2-yl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
2-methyl-3-[2-[4-(2-methylphenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.003
2-methyl-3-[2-[4-(2-nitrobenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0063
2-methyl-3-[2-[4-(2-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
2-methyl-3-[2-[4-(3-methylbenzoyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0008
2-methyl-3-[2-[4-(4-nitrophenyl)piperazin-1-yl]-2-oxoethoxy]-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
2-methyl-3-[2-[4-(pyridin-2-ylcarbonyl)piperazin-1-yl]ethoxy]-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.000456
2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro-1H-isoindole-4,5-diol
Homo sapiens
at pH 7.5 and 25°C
0.0059 - 0.0076
2-[5-[(2S)-1-benzylpiperidin-2-yl]-3-(oxan-4-yl)-1H-1,2,4-triazol-1-yl]ethan-1-ol
0.001657
3-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-3-oxopropanoic acid
Homo sapiens
at pH 7.5 and 25°C
0.0091
3-[2-(4-(3-chlorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.001
3-[2-(4-(3-fluorophenyl)piperazin-1-yl)-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-(4-benzoylpiperazin-1-yl)ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0059
3-[2-[4-(2-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-[4-(2-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(3,5-dimethoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0081
3-[2-[4-(3,5-dimethylphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-[4-(3-methoxybenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(3-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0039
3-[2-[4-(4-chlorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0008
3-[2-[4-(4-fluorobenzoyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.0014
3-[2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.01
3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(dichloroacetyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.01
3-[2-[4-(diphenylmethyl)piperazin-1-yl]-2-oxoethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
IC50 above 0.01 mM, at pH 7.8 and 37°C
0.0016
3-[2-[4-(furan-2-ylcarbonyl)piperazin-1-yl]ethoxy]-2-methyl-4H-pyran-4-one
Homo sapiens
-
at pH 7.8 and 37°C
0.000154
4-(5-[[1-(2,3-dihydroxypropyl)piperidin-4-yl]amino]-1,3-dihydro-2H-isoindole-2-sulfonyl)benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.001177
4-[(5-amino-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.00057
4-[(5-hydroxy-1,3-dihydro-2H-isoindol-2-yl)sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.648
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
Homo sapiens
pH 8.0, temperature not specified in the publication
0.00196
4-[5-(cyclohexylamino)-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.000416
4-[5-[(1-benzylpiperidin-4-yl)amino]-1,3-dihydro-2H-isoindole-2-sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.00015
4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]-N-ethylpiperidine-1-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.001346
4-[[5-(piperazin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.004371
4-[[5-(piperidin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.000195
4-[[5-(piperidin-4-ylamino)-1,3-dihydro-2H-isoindol-2-yl]sulfonyl]benzene-1,3-diol
Homo sapiens
at pH 7.5 and 25°C
0.00058
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-(pyridin-4-yl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000068
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-(2-methylpropyl)piperidin-4-yl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000017
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000059
5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-N-[1-[(pyridin-4-yl)methyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00061
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00095
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-[(morpholin-4-yl)methyl]phenyl]-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00061
5-(5-chloro-2,4-dihydroxyphenyl)-N-[(2,4-dichlorophenyl)methyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000028
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-(cyclopropylmethyl)piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00016
5-(5-chloro-2,4-dihydroxyphenyl)-N-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00038
5-(5-chloro-2,4-dihydroxyphenyl)-N-[4-(dimethylamino)phenyl]-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.0157 - 0.0178
5-[(1,3-benzodioxol-5-yloxy)methyl]-N-(imidazo[1,2-a]pyridin-3-ylmethyl)-N-methyl-1H-pyrazole-3-carboxamide
0.00161
6-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-6-oxohexanoic acid
Homo sapiens
at pH 7.5 and 25°C
0.000629
9-(4-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]piperidin-1-yl)-9-oxononanoic acid
Homo sapiens
at pH 7.5 and 25°C
0.0113
AUY922
Homo sapiens
pH and temperature not specified in the publication
0.087 - 0.6
AZD7545
0.013 - 108
Dichloroacetate
0.03559 - 0.04679
ethyl 5-benzyl-2-[([2-[(cyclohexylamino)carbonothioyl]hydrazine]carbonothioyl)amino]-3-thiophenecarboxylate
0.00013
methyl 4-[[5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carbonyl]amino]piperidine-1-sulfinate
Homo sapiens
pH and temperature not specified in the publication
0.00021
N-(1-acetylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000025
N-(1-benzylpiperidin-4-yl)-5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000357
N1-(2-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]ethyl)-L-aspartamide
Homo sapiens
at pH 7.5 and 25°C
0.000067
N1-(3-[[2-(2,4-dihydroxybenzene-1-sulfonyl)-2,3-dihydro-1H-isoindol-5-yl]amino]propyl)-L-aspartamide
Homo sapiens
at pH 7.5 and 25°C
0.23 - 1.079
radicicol
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.006
-
PDK3 activity with E1
0.008
purified recombinant enzyme
0.02
-
about, with E2 bound to E1, 0.2 mM ATP
0.03
-
about, with E2 bound to E1 in presence of NADH/NAD+ and acetyl-CoA, 0.2 mM ATP
0.037
-
about, with free E2, 0.2 mM ATP
0.064
-
PDK3 activity with reconstituted PDC
0.066
-
about, with free E2 in presence of NADH/NAD+ and acetyl-CoA, 0.2 mM ATP
0.44
-
isozyme PDK3, pH 7.3, 30°C
0.69
-
isozyme PDK2, pH 7.3, 30°C
1.1
-
purified isozyme PDK2
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
7 - 7.4
-
assay at
7.3
-
assay at
7.4
-
assay at
additional information
-
different buffer systems
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8
isoform PDK3 shows best enzyme activity in the pH range of 7.0-8.0. Enzyme activity is lost under acidic pH (2.0-6.0)
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
-
activity assay
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
high PDK expression
Manually annotated by BRENDA team
-
mainly isozyme PDK2
Manually annotated by BRENDA team
-
post-mortem brain extracts from patients with Alzheimer disease exhibit a decrease in PDK1 expression compared with nondemented patients
Manually annotated by BRENDA team
-
primary, determination of PDK4 expression level in presence or absence of farnesoid X receptor agonists
Manually annotated by BRENDA team
-
The human liver cancer cell line HepG3B was obtained from the cell bank of the Institute of Biochemistry and Cell Biology
Manually annotated by BRENDA team
-
i.e. NSCLC, reduced PDK/PDH activity, PDK1 and PDH expression patterns
Manually annotated by BRENDA team
-
high PDK expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
BCR-ABL, JAK2, and FLT3 are co-localized with PDHK1
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PDK2_HUMAN
407
0
46154
Swiss-Prot
Mitochondrion (Reliability: 5)
PDK3_HUMAN
406
0
46939
Swiss-Prot
Mitochondrion (Reliability: 2)
PDK4_HUMAN
411
0
46469
Swiss-Prot
Mitochondrion (Reliability: 2)
PDK1_HUMAN
436
0
49244
Swiss-Prot
Mitochondrion (Reliability: 1)
PDK2_HUMAN
407
0
46154
Swiss-Prot
-
PDK3_HUMAN
406
0
46939
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45066
-
x * 45066, isozyme PDK2, DNA sequence determination
45806
-
x * 45806, recombinant isozyme PDK2, detagged, amino acid determination
45816
-
2 * 45816, sedimentation equilibrium centrifugation analysis in presence of 1% ethylene glycol, 0.1% Pluronics F68, and 0.15 M NaCl
45883
-
x * 45883, isozyme PDK3, DNA sequence determination
46230
-
x * 46230, isozyme PDK4, DNA sequence determination
46504
-
x * 46504, recombinant isozyme PDK3, detagged, amino acid determination
47500
x * 47500, recombinant His-tagged enzyme, SDS-PAGE
48391
-
x * 48391, isozyme PDK1, DNA sequence determination
90220
-
isozyme PDK2, sedimentation equilibrium centrifugation analysis
additional information
-
sedimentation equilibrium centrifugation analysis of the pyruvate dehydrogenase complex and components
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
dimer or tetramer
-
effects of ligand binding on distal structure of PDHK2, analytical ultracentrifugation, structure, overview
homodimer
-
-
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
tyrosine phosphorylation at Tyr243 of PDHK1 is required for enzyme activity and occurs in human cancers by diverse oncogenic tyrosine kinases, localized to different mitochondrial compartments, tyrosine phosphorylation by FGFR1 enhances PDHK1 activity by promoting ATP and pyruvate dehydrogenase complex binding. FGFR1 activates PDHK1 through direct phosphorylation at multiple tyrosine sites. Phosphorylation at both Y243 and Y244, but not Y136 may be required to promote ATP binding to PDHK1, while Y136 phosphorylation may only function to enhance binding between PDHK1 and pyruvate dehydrogenase complex
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with inhibitor (S)-3-amino-4-(4-((2-((2,4-dihydroxyphenyl)sulfonyl)isoindolin-5-yl)-amino)piperidin-1-yl)-4-oxobutanamide, hanging drop vapor diffusion method, using 9% (v/v) 2-propanol, 0.1 M MgCl2, 50 mM ammonium sulfate, and 0.1 M sodium acetate (pH 5.6). Enzyme in complex with inhibitor 4-((5-(piperidin-4-ylamino)isoindolin-2-yl)sulfonyl)benzene-1,3-diol, hanging drop vapor diffusion method, using 0.9 M ammonium tartrate, 0.1 M sodium acetate pH 4.6
isozyme PDHK3 in an asymmetric complex with L2, hanging-drop vapor diffusion technique, mixing of 0.002 ml of protein solution containing 3-5 mg/ml of the PDHK3/L2 complex, 20 mM Tris-HCl, pH 8.0, 100 mM NaCl, 5 mM DTT, and 2.5% v/v ethylene glycol with an equal volume of reservoir solution containing 100 mM histidine, pH 6.4, 30 mM EDTA, and 7% v/v 2,4-methyl penthane diol, X-ray diffraction structure determination and analysis at 2.5 A resolution, molecular replacement, modelling
-
isozyme PDK1 in complex with inhibitors AZD7545 and dichloroacetate, hanging-drop vapor-diffusion method, mixing of 2 ml of PDK1 solution with 50 mg/ml untagged PDK1 in 50 mM potassium phosphate, pH 7.5, 250 mM KCl, 800 mM lysine, 5% glycerol, and 20 mM DTT with 2 ml of well solution containing 0.42 M Na-K-tartrate, 0.1 M Na citrate, pH 5.6,at 20°C, 1 week, X-ray diffraction structure determination and analysis at 1.9-2.6 A resolution
isozyme PDK4 complexed with either AMPPNP, ADP or inhibitor M77976, screening using the sitting drop vapour diffusion method at 20°C, optimized hanging drop vapour diffusion method mixing PDK4 with 10 mM MgCl2, and 5 mM AMPPNP, the reservoir solution contains 1.7 M ammonium sulfate, 2% PEG 400, and Na HEPES, pH 7.1, soaking the PDK4-AMPPNP crystals in 5 mM ADP or 1 mM M77976, X-ray diffraction structure determination and analysis at 1.85-2.53 A resolution, molecular replacement using rat PDK2, PDB entry 1jm6, modeling
purified recombinant residues A8-T399 of isozyme PDHK2 free or in complex with ADP and chloroacetate, ATP, Nov3r, Pfz3, or AZ12, hanging drop vapour diffusion method, protein solution contains 10 mg/ml protein, 20 mM Tris-HCl, pH 8.0, 0.15 M NaCl, and 1 mM DTT, versus 0.1 M sodium acetate, pH 5.6-5.8, 6-9% 2-propanol, and 75-125 mM MgCl2, 4°C, 2 weeks, complexing with ligands by soaking of PDHK2 crystals in solutions containing 10 mM ATP, 10 mM ADP and 100 mM dichloroacetate, or 1 mM of Nov3r, Pfz3, or AZ12, cryoprotection by 30-35% glycerol, X-ray diffraction structure determination and analysis at 2.2-3.0 A resolution
-
pyruvate dehydrogenase kinase 3 bound to ATP and the lipoyl domain 2 of human pyruvate dehydrogenase complex, X-ray structure determination and analysis at 1.0 A resolution, modeling of closed and open conformation
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D117A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
D164A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
D172A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
D382A/W383A
-
substitutions in the DW-motif
E162A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
E170A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
E179A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
F32A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
F35A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
F48A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
H115A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
I111A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
I157A
-
site-directed mutagenesis, the mutant enzyme shows increased inhibition by dichloroacetate compared to the wild-type PDHK2
I161A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
L140A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
L27A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
L53A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
P142A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is unaltered compared to the wild-type isozyme PDK3
R112A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R114A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
R149A
-
substitution of an interacting residue of the DW-motif, mutant shows drastic increase in apparent IC50 value for dichloroacetate, increased affinity for ADP and ATP
R154A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R158A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R196A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
S83A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
T175A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is unaltered compared to the wild-type isozyme PDK3
W383F
-
site-directed mutagenesis of isozyme PDHK2, the mutant shows unaltered catalytic activity compared to the wild-type isozyme PDHK2, but altered ligand binding and higher sensitivity to inhibition by pyruvate and ADP
Y145F
-
substitution of an interacting residue of the DW-motif, increased affinity for ADP and ATP
Y145F/R149A
-
mutant shows drastic increase in apparent IC50 value for dichloroacetate
Y80A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni charged HiTrap column chromatography
nickel column chromatography
recombinant His-tagged isozymes PDK2 and PDK3 from Escherichia coli BL21(DE3)
-
recombinant His-tagged PDK2, E2, and E3 by nickel affinity chromatography, the His-tag is removable
-
recombinant His-tagged PDK3 from Escherichia coli strain BL21
-
recombinant His-tagged protein from Sf9 insect cells, to near homogeneity
recombinant N-terminally His-tagged residues A8-T399 of isozyme PDHK2 from insect cells by nickel affinity chromatography, the His-tag is cleaved off by thrombin
-
Superdex 200 gel filtration
with nickel-nitrilotriacetic acid resin and subsequently on a Superdex S200 column
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-expression of GST-tagged PDHK2 with E1 and E2 components of PDC in Escherichia coli strain BL21(DE3)
-
co-expression of PDK2, E2, and E3 as His-tagged proteins
-
expressed as a N-terminal His6-tagged SUMO fusion protein
expressed in Escherichia coli
expressed in Escherichia coli BL-21 cells
expression analysis and mRNA level determination for isozymes PDK2 and PDK4 in response to several effectors
-
expression in HCT-116 cells
-
expression of GST-tagged PDHK1 in 293T cells, transient co-transfection with wild-type FGFR1 leads to tyrosine phosphorylation of PDHK1, but not in cells co-expressing a kinase dead form of FGFR1. Expression of phosphorylation-deficient, catalytic hypomorph PDHK1 mutants in cancer cells leading to decreased cell proliferation under hypoxia and increased oxidative phosphorylation with enhanced mitochondrial utilization of pyruvate, and expression in xenograft nude mice leads to reduced tumor growth
expression of isozyme PDK4 in Escherichia coli, unmodified and modified enzyme
-
expression of isozyme PDK4-luciferase in McA-RH7777 cells using the adenovirus transfection method, PDK2 and PDK4 expression analysis, overview
-
expression of N-terminally His-tagged residues A8-T399 of isozyme PDHK2 in Trichoplusia ni TN5B1-4 insect cells using the baculovirus infection system
-
expression of wild-type and mutant PDHK2 isozymes
-
gene pdk4, DNA and amino sequence determination and analysis, genomic organisation, functional expression of the His-tagged enzyme in Spodoptera frugiperda Sf9 cells via bacuovirus infection system
His-tagged PDK3 overexpression in Escherichia coli strain BL21
-
isozymes PDK2 and PDK3, expression in Escherichia coli BL21(DE3) as His-tagged proteins
-
overexpression of isozyme PDK3 in Escherichia coli BL21(DE3) as His-tagged protein
-
overexpression of PDK1 in the rat CNS cell line B12 confers resistance to amyloid-beta peptide and other neurotoxins. Cells expressing PDK1 maintain a lower mitochondrial membrane potential and decreased ROS production with or without exposure to toxins
-
PDK4 gene is located in q21.3 region of chromosome 7, DNA sequence analysis, genomic organization, DNA sequence determination of the partial proximal promotor
-
PDK4, expression of PDK2 and PDK4 in 29T cells, transient expression of PDK4 and PDK4 promoter in CV-1 cells, expression is regulated by retinoic acids and trichostatin A, the proximal promoter contains two retinoic acid response elements binding retinoid X receptor alpha and retinoid acid receptor alpha leading to transcriptional activation, the PDK4 expression activation by all components is prevented by interaction of p300/CBP with E1A, expression analysis, overview
-
wild-type and variant human PDK2 proteins are expressed as N-terminal His6-tagged SUMO fusions
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
apoptosis-inducing agents such as tumor necrosis factor alpha, C2-ceramide, and linoleic acid suppress PDK4 mRNA levels
cotransfection with plasmids expressing either E2F1 or E2F2 activates Pdk2/luciferase transcription. E2F1 binds less well to the Pdk2 promoter when p53 is induced with zinc
-
FOXO1-mediated 4fold upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
-
hepatic enzyme levels are highly induced in human patients with non-alcoholic steatohepatitis as well as in hepatocytes treated with oleic acid
-
HIF-1alpha is a heterodimeric transcription factor that regulates cellular adaptation to hypoxia and induces the transcription of pyruvate dehydrogenase kinase 1
-
Pdk2 transcription decreases upon addition of nutlin-3a, nutlin-3a can produce off-target effects, upon reduction of p53, the effect of nutlin-3a upon Pdk2 protein decreases. A histone deacetylase inhibitor, trichostatin A, partially prevents repression of Pdk2 transcription by p53
-
post-mortem brain extracts from patients with Alzheimer disease exhibit a decrease in PDK1 expression compared with nondemented patients
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of the active pyruvate dehydrogenase complex PDC
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
development of specific inhibitors of PDK4 has become an especially important focus for the pharmaceutical management of diabetes and obesity
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rowles, J.; Scherer, S.W.; Xi, T.; Majer, M.; Nickle, D.C.; Rommens, J.M.; Popov, K.M.; Harris, R.A.; Riebow, N.L.; et al.
Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human
J. Biol. Chem.
271
22376-22382
1996
Homo sapiens (Q16654), Homo sapiens
Manually annotated by BRENDA team
Baker, J.C.; Yan, X.; Peng, T.; Kasten, S.; Roche, T.E.
Marked differences between two isoforms of human pyruvate dehydrogenase kinase
J. Biol. Chem.
275
15773-15781
2000
Homo sapiens
Manually annotated by BRENDA team
Roche, T.E.; Baker, J.C.; Yan, X.; Hiromasa, Y.; Gong, X.; Peng, T.; Dong, J.; Turkan, A.; Kasten, S.A.
Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms
Prog. Nucleic Acid Res. Mol. Biol.
70
33-75
2001
Arabidopsis thaliana, Bos taurus, Homo sapiens, Mammalia, Rattus norvegicus, Zea mays
Manually annotated by BRENDA team
Korotchkina, L.G.; Patel, M.S.
Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase
J. Biol. Chem.
276
37223-37229
2001
Homo sapiens, Mammalia, Rattus norvegicus
Manually annotated by BRENDA team
Roche, T.E.; Hiromasa, Y.; Turkan, A.; Gong, X.; Peng, T.; Yan, X.; Kasten, S.A.; Bao, H.; Dong, J.
Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1
Eur. J. Biochem.
270
1050-1056
2003
Homo sapiens, Mammalia, Rattus norvegicus
Manually annotated by BRENDA team
Kwon, H.S.; Harris, R.A.
Mechanisms responsible for regulation of pyruvate dehydrogenase kinase 4 gene expression
Adv. Enzyme Regul.
44
109-121
2004
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Savkur, R.S.; Bramlett, K.S.; Michael, L.F.; Burris, T.P.
Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor
Biochem. Biophys. Res. Commun.
329
391-396
2005
Homo sapiens, Mus musculus, Mus musculus C57BL/6, Rattus norvegicus
Manually annotated by BRENDA team
Tuganova, A.; Popov, K.M.
Role of protein-protein interactions in the regulation of pyruvate dehydrogenase kinase activity
Biochem. J.
387
147-153
2005
Homo sapiens
Manually annotated by BRENDA team
Mayers, R.M.; Leighton, B.; Kilgour, E.
PDH kinase inhibitors: a novel therapy for Type II diabetes?
Biochem. Soc. Trans.
33
367-370
2005
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Bao, H.; Kasten, S.A.; Yan, X.; Roche, T.E.
Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by slowing down the rate of dissociation of ADP
Biochemistry
43
13432-13441
2004
Homo sapiens
Manually annotated by BRENDA team
Knoechel, T.R.; Tucker, A.D.; Robinson, C.M.; Phillips, C.; Taylor, W.; Bungay, P.J.; Kasten, S.A.; Roche, T.E.; Brown, D.G.
Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands
Biochemistry
45
402-415
2006
Homo sapiens
Manually annotated by BRENDA team
Kato, M.; Chuang, J.L.; Tso, S.C.; Wynn, R.M.; Chuang, D.T.
Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex
EMBO J.
24
1763-1774
2005
Homo sapiens
Manually annotated by BRENDA team
Abbot, E.L.; McCormack, J.G.; Reynet, C.; Hassall, D.G.; Buchan, K.W.; Yeaman, S.J.
Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells
FEBS J.
272
3004-3014
2005
Homo sapiens
Manually annotated by BRENDA team
Korotchkina, L.G.; Sidhu, S.; Patel, M.S.
R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase
Free Radic. Res.
38
1083-1092
2004
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Spriet, L.L.; Tunstall, R.J.; Watt, M.J.; Mehan, K.A.; Hargreaves, M.; Cameron-Smith, D.
Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting
J. Appl. Physiol.
96
2082-2087
2004
Homo sapiens
Manually annotated by BRENDA team
Watt, M.J.; Heigenhauser, G.J.; LeBlanc, P.J.; Inglis, J.G.; Spriet, L.L.; Peters, S.J.
Rapid upregulation of pyruvate dehydrogenase kinase activity in human skeletal muscle during prolonged exercise
J. Appl. Physiol.
97
1261-1267
2004
Homo sapiens
Manually annotated by BRENDA team
Turvey, E.A.; Heigenhauser, G.J.; Parolin, M.; Peters, S.J.
Elevated n-3 fatty acids in a high-fat diet attenuate the increase in PDH kinase activity but not PDH activity in human skeletal muscle
J. Appl. Physiol.
98
350-355
2005
Homo sapiens
Manually annotated by BRENDA team
Hiromasa, Y.; Roche, T.E.
Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase
J. Biol. Chem.
278
33681-33693
2003
Homo sapiens
Manually annotated by BRENDA team
Koukourakis, M.I.; Giatromanolaki, A.; Sivridis, E.; Gatter, K.C.; Harris, A.L.
Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non small cell lung cancer and tumor-associated stroma
Neoplasia
7
1-6
2005
Homo sapiens
Manually annotated by BRENDA team
Kwon, H.; Huang, B.; Jeoung, N.H.; Wu, P.; Steussy, C.N.; Harris, R.A.
Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression
Biochim. Biophys. Acta
1759
141-151
2006
Homo sapiens
Manually annotated by BRENDA team
Kim, J.W.; Tchernyshyov, I.; Semenza, G.L.; Dang, C.V.
HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia
Cell Metab.
3
177-185
2006
Homo sapiens
Manually annotated by BRENDA team
Roche, T.E.; Hiromasa, Y.
Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer
Cell. Mol. Life Sci.
64
830-849
2007
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Klyuyeva, A.; Tuganova, A.; Popov, K.M.
Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2
FEBS Lett.
581
2988-2992
2007
Homo sapiens
Manually annotated by BRENDA team
Hiromasa, Y.; Hu, L.; Roche, T.E.
Ligand-induced effects on pyruvate dehydrogenase kinase isoform 2
J. Biol. Chem.
281
12568-12579
2006
Homo sapiens
Manually annotated by BRENDA team
Tso, S.C.; Kato, M.; Chuang, J.L.; Chuang, D.T.
Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complex
J. Biol. Chem.
281
27197-27204
2006
Homo sapiens
Manually annotated by BRENDA team
Zhang, Y.; Ma, K.; Sadana, P.; Chowdhury, F.; Gaillard, S.; Wang, F.; McDonnell, D.P.; Unterman, T.G.; Elam, M.B.; Park, E.A.
Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression
J. Biol. Chem.
281
39897-39906
2006
Homo sapiens
Manually annotated by BRENDA team
Chokkalingam, K.; Jewell, K.; Norton, L.; Littlewood, J.; van Loon, L.J.; Mansell, P.; Macdonald, I.A.; Tsintzas, K.
High-fat/low-carbohydrate diet reduces insulin-stimulated carbohydrate oxidation but stimulates nonoxidative glucose disposal in humans: An important role for skeletal muscle pyruvate dehydrogenase kinase 4
J. Clin. Endocrinol. Metab.
92
284-292
2007
Homo sapiens
Manually annotated by BRENDA team
Devedjiev, Y.; Steussy, C.N.; Vassylyev, D.G.
Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications
J. Mol. Biol.
370
407-416
2007
Homo sapiens
Manually annotated by BRENDA team
Kato, M.; Li, J.; Chuang, J.L.; Chuang, D.T.
Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol
Structure
15
992-1004
2007
Homo sapiens (Q15118), Homo sapiens
Manually annotated by BRENDA team
Li, J.; Kato, M.; Chuang, D.T.
Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate
J. Biol. Chem.
284
34458-34467
2009
Homo sapiens
Manually annotated by BRENDA team
Kukimoto-Niino, M.; Tokmakov, A.; Terada, T.; Ohbayashi, N.; Fujimoto, T.; Gomi, S.; Shiromizu, I.; Kawamoto, M.; Matsusue, T.; Shirouzu, M.; Yokoyama, S.
Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4
Acta Crystallogr. Sect. D
67
763-773
2011
Homo sapiens (Q16654), Homo sapiens
Manually annotated by BRENDA team
Contractor, T.; Harris, C.R.
p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2
Cancer Res.
72
560-567
2012
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Newington, J.T.; Rappon, T.; Albers, S.; Wong, D.Y.; Rylett, R.J.; Cumming, R.C.
Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid beta and other toxins by decreasing mitochondrial respiration and reactive oxygen species production
J. Biol. Chem.
287
37245-37258
2012
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Piao, L.; Sidhu, V.K.; Fang, Y.H.; Ryan, J.J.; Parikh, K.S.; Hong, Z.; Toth, P.T.; Morrow, E.; Kutty, S.; Lopaschuk, G.D.; Archer, S.L.
FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate
J. Mol. Med.
91
333-346
2013
Homo sapiens, Rattus norvegicus, Rattus norvegicus Fawn-Hooded
Manually annotated by BRENDA team
Hitosugi, T.; Fan, J.; Chung, T.W.; Lythgoe, K.; Wang, X.; Xie, J.; Ge, Q.; Gu, T.L.; Polakiewicz, R.D.; Roesel, J.L.; Chen, G.Z.; Boggon, T.J.; Lonial, S.; Fu, H.; Khuri, F.R.; Kang, S.; Chen, J.
Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism
Mol. Cell
44
864-877
2011
Homo sapiens (Q15118), Homo sapiens
Manually annotated by BRENDA team
Dlamini, Z.; Ntlabati, P.; Mbita, Z.; Shoba-Zikhali, L.
Pyruvate dehydrogenase kinase 4 (PDK4) could be involved in a regulatory role in apoptosis and a link between apoptosis and insulin resistance
Exp. Mol. Pathol.
98
574-584
2015
Homo sapiens (Q16654)
Manually annotated by BRENDA team
Fereidoonnezhad, M.; Faghih, Z.; Mojaddami, A.; Sakhteman, A.; Rezaei, Z.
A comparative docking studies of dichloroacetate analogues on four isozymes of pyruvate dehydrogenase kinase in humans
Indian J. Pharm. Edu. Res.
50
S32-S38
2016
Homo sapiens (Q15118), Homo sapiens (Q15119), Homo sapiens (Q15120), Homo sapiens (Q16654)
-
Manually annotated by BRENDA team
Meng, T.; Zhang, D.; Xie, Z.; Yu, T.; Wu, S.; Wyder, L.; Regenass, U.; Hilpert, K.; Huang, M.; Geng, M.; Shen, J.
Discovery and optimization of 4,5-diarylisoxazoles as potent dual inhibitors of pyruvate dehydrogenase kinase and heat shock protein 90
J. Med. Chem.
57
9832-9843
2014
Homo sapiens (Q15118)
Manually annotated by BRENDA team
Lee, S.J.; Jeong, J.Y.; Oh, C.J.; Park, S.; Kim, J.Y.; Kim, H.J.; Doo Kim, N.; Choi, Y.K.; Do, J.Y.; Go, Y.; Ha, C.M.; Ha, C.M.; Choi, J.Y.; Huh, S.; Ho Jeoung, N.; Lee, K.U.; Choi, H.S.; Wang, Y.; Park, K.G.; Harris, R.A.; Lee, I.K.
Pyruvate dehydrogenase kinase 4 promotes vascular calcification via SMAD1/5/8 phosphorylation
Sci. Rep.
5
16577
2015
Homo sapiens (Q16654), Homo sapiens
Manually annotated by BRENDA team
Jung, G.S.; Jeon, J.H.; Choi, Y.K.; Jang, S.Y.; Park, S.Y.; Kim, S.W.; Byun, J.K.; Kim, M.K.; Lee, S.; Shin, E.C.; Lee, I.K.; Kang, Y.N.; Park, K.G.
Pyruvate dehydrogenase kinase regulates hepatitis C virus replication
Sci. Rep.
6
30846
2016
Homo sapiens
Manually annotated by BRENDA team
Zhang, W.; Hu, X.; Chakravarty, H.; Yang, Z.; Tam, K.
Identification of novel pyruvate dehydrogenase kinase 1 (PDK1) inhibitors by kinase activity-based high-throughput screening for anticancer therapeutics
ACS Comb. Sci.
20
660-671
2018
Homo sapiens (Q15118)
Manually annotated by BRENDA team
Zhang, M.; Zhao, Y.; Li, Z.; Wang, C.
Pyruvate dehydrogenase kinase 4 mediates lipogenesis and contributes to the pathogenesis of nonalcoholic steatohepatitis
Biochem. Biophys. Res. Commun.
495
582-586
2018
Homo sapiens, Mus musculus (Q16654)
Manually annotated by BRENDA team
Cao, W.; Wang, Z.; Han, X.; Liu, J.; Wang, W.
In vitro cytotoxicity screening to identify novel anti-osteosarcoma therapeutics targeting pyruvate dehydrogenase kinase 2
Bioorg. Med. Chem. Lett.
29
126665
2019
Homo sapiens (Q15119)
Manually annotated by BRENDA team
Guo, F.; Zhao, S.; Li, X.
Discovery of novel pyruvate dehydrogenase kinases inhibitors by screening of an in-house small molecule library for anti-lung cancer therapeutics
Bioorg. Med. Chem. Lett.
29
291-296
2019
Homo sapiens (Q15118)
Manually annotated by BRENDA team
Xiang, S.; Huang, D.; He, Q.; Li, J.; Tam, K.; Zhang, S.; He, Y.
Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A High-throughput virtual screening, synthesis and biological validation
Eur. J. Med. Chem.
203
112579
2020
Homo sapiens
Manually annotated by BRENDA team
Anwar, S.; Kar, R.; Haque, M.; Dahiya, R.; Gupta, P.; Islam, A.; Ahmad, F.; Hassan, M.
Effect of pH on the structure and function of pyruvate dehydrogenase kinase 3 Combined spectroscopic and MD simulation studies
Int. J. Biol. Macromol.
147
768-777
2020
Homo sapiens (Q15120)
Manually annotated by BRENDA team
Mohammad, T.; Arif, K.; Alajmi, M.; Hussain, A.; Islam, A.; Rehman, M.; Hassan, I.
Identification of high-affinity inhibitors of pyruvate dehydrogenase kinase-3 towards therapeutic management of cancer
J. Biomol. Struct. Dyn.
39
586-594
2021
Homo sapiens (Q15120)
Manually annotated by BRENDA team
Deng, X.; Wang, Q.; Cheng, M.; Chen, Y.; Yan, X.; Guo, R.; Sun, L.; Li, Y.; Liu, Y.
Pyruvate dehydrogenase kinase 1 interferes with glucose metabolism reprogramming and mitochondrial quality control to aggravate stress damage in cancer
J. Cancer
11
962-973
2020
Homo sapiens
Manually annotated by BRENDA team
Tso, S.; Lou, M.; Wu, C.; Gui, W.; Chuang, J.; Morlock, L.; Williams, N.; Wynn, R.; Qi, X.; Chuang, D.
Development of dihydroxyphenyl sulfonylisoindoline derivatives as liver-targeting pyruvate dehydrogenase kinase inhibitors
J. Med. Chem.
60
1142-1150
2017
Homo sapiens (Q15119)
Manually annotated by BRENDA team