Literature summary for 2.3.1.B43 extracted from

Fiorentino, F.; Castiello, C.; Mai, A.; Rotili, D.
Therapeutic potential and activity modulation of the protein lysine deacylase sirtuin 5 (2022), J. Med. Chem., 65, 9580-9606.

Search for more literature for 2.3.1.B43

Inhibitors

Inhibitors	Comment	Organism
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-ethyl-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-ethyl-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
3-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Homo sapiens
3-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Mus musculus
4-(5-[(1E)-2-cyano-3-[3-(methylcarbamoyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid	-	Homo sapiens
4-(5-[(1E)-2-cyano-3-[3-(methylcarbamoyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid	-	Mus musculus
4-(5-[(1E)-2-cyano-3-[4-cyano-3-(trifluoromethyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid	-	Homo sapiens
4-(5-[(1E)-2-cyano-3-[4-cyano-3-(trifluoromethyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid	-	Mus musculus
4-(5-[(1E)-3-[4-chloro-3-(trifluoromethyl)anilino]-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid	-	Homo sapiens
4-(5-[(1E)-3-[4-chloro-3-(trifluoromethyl)anilino]-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid	-	Mus musculus
4-(5-[(Z)-[1-(3-chloro-4-methylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid	-	Homo sapiens
4-(5-[(Z)-[1-(3-chloro-4-methylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid	-	Mus musculus
4-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-5-carboxylic acid	-	Homo sapiens
4-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-5-carboxylic acid	-	Mus musculus
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]-3-methylbenzoic acid	-	Homo sapiens
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]-3-methylbenzoic acid	-	Mus musculus
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Homo sapiens
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Mus musculus
4-[5-[(1E)-2-cyano-3-(3,5-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Homo sapiens
4-[5-[(1E)-2-cyano-3-(3,5-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Mus musculus
4-[5-[(1E)-2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Homo sapiens
4-[5-[(1E)-2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Mus musculus
4-[5-[(1E)-3-(4-chloro-3-nitroanilino)-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Homo sapiens
4-[5-[(1E)-3-(4-chloro-3-nitroanilino)-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid	-	Mus musculus
5-([4-[(2-chlorophenyl)methoxy]-3-methoxyphenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
5-([4-[(2-chlorophenyl)methoxy]-3-methoxyphenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
5-([4-[(4-bromophenyl)methoxy]phenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
5-([4-[(4-bromophenyl)methoxy]phenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
5-[[4-(benzyloxy)phenyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
5-[[4-(benzyloxy)phenyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Homo sapiens
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	-	Mus musculus
6-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-4-carboxylic acid	-	Homo sapiens
6-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-4-carboxylic acid	-	Mus musculus
N-([3-[(2-[[2-(1H-indol-3-yl)ethyl]amino]-5-nitropyrimidin-4-yl)amino]propyl]carbamothioyl)-beta-alanine	-	Homo sapiens
N-([3-[(2-[[2-(1H-indol-3-yl)ethyl]amino]-5-nitropyrimidin-4-yl)amino]propyl]carbamothioyl)-beta-alanine	-	Mus musculus
N-[(3-[[2-(benzylamino)-5-(ethoxycarbonyl)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[2-(benzylamino)-5-(ethoxycarbonyl)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[(3-[[2-(benzylamino)-5-fluoropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[2-(benzylamino)-5-fluoropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[(3-[[2-(benzylamino)-5-nitropyridin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[2-(benzylamino)-5-nitropyridin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[(3-[[2-(benzylamino)-5-nitropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[2-(benzylamino)-5-nitropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[(3-[[2-(benzylamino)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[2-(benzylamino)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[(3-[[5-(ethoxycarbonyl)-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[5-(ethoxycarbonyl)-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[(3-[[6-(benzylamino)-3-nitropyridin-2-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Homo sapiens
N-[(3-[[6-(benzylamino)-3-nitropyridin-2-yl]amino]propyl)carbamothioyl]-beta-alanine	-	Mus musculus
N-[[3-([5-nitro-2-[(2-phenylethyl)amino]pyrimidin-4-yl]amino)propyl]carbamothioyl]-beta-alanine	-	Homo sapiens
N-[[3-([5-nitro-2-[(2-phenylethyl)amino]pyrimidin-4-yl]amino)propyl]carbamothioyl]-beta-alanine	-	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
cytosol	-	Mus musculus	5829	-
mitochondrion	mitochondrial matrix	Homo sapiens	5739	-
mitochondrion	mitochondrial matrix	Mus musculus	5739	-
nucleus	-	Homo sapiens	5634	-
nucleus	-	Mus musculus	5634	-
peroxisome	-	Homo sapiens	5777	-
peroxisome	-	Mus musculus	5777	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
[p53]-N6-succinyl-L-lysine + NAD+ + H2O	Homo sapiens	p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis	[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[p53]-N6-succinyl-L-lysine + NAD+ + H2O	Mus musculus	p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis	[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O	Homo sapiens	desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells	[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O	Mus musculus	desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells	[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O	Homo sapiens	desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation	[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O	Mus musculus	desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation	[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[superoxide dismutase 1]-N6-acetyl-L-lysine + NAD+ + H2O	Mus musculus	SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification	[superoxide dismutase 1]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide	-	?
[superoxide dismutase 1]-N6-succinal-L-lysine + NAD+ + H2O	Homo sapiens	SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification	[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9NXA8	-	-
Mus musculus	Q8K2C6	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
adipose tissue	-	Homo sapiens	-
brain	-	Homo sapiens	-
heart	-	Homo sapiens	-
kidney	-	Homo sapiens	-
liver	-	Homo sapiens	-
muscle	-	Homo sapiens	-
pancreatic ductal adenocarcinoma cell	-	Homo sapiens	-
testis	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	SIRT5 has the highest catalytic efficiency for deglutarylation, followed by desuccinylation and demalonylation and low deacetylation activity	Homo sapiens	?	-	-
additional information	SIRT5 has the highest catalytic efficiency for deglutarylation, followed by desuccinylation and demalonylation and low deacetylation activity	Mus musculus	?	-	-
[mitochondrial glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O	-	Homo sapiens	[mitochondrial glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[mitochondrial glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O	-	Mus musculus	[mitochondrial glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[p53]-N6-succinyl-L-lysine + NAD+ + H2O	p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis	Homo sapiens	[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[p53]-N6-succinyl-L-lysine + NAD+ + H2O	p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis	Mus musculus	[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[p53]-N6-succinyl-L-lysine + NAD+ + H2O	-	Homo sapiens	[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[p53]-N6-succinyl-L-lysine + NAD+ + H2O	-	Mus musculus	[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[PKM2]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation of PKM2 at Lys311	Homo sapiens	[PKM2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[PKM2]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation of PKM2 at Lys311	Mus musculus	[PKM2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells	Homo sapiens	[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells	Mus musculus	[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation at Lys280	Homo sapiens	[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation at Lys280	Mus musculus	[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation	Homo sapiens	[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O	desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation	Mus musculus	[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O	-	Homo sapiens	[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O	-	Mus musculus	[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[superoxide dismutase 1]-N6-acetyl-L-lysine + NAD+ + H2O	SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification	Mus musculus	[superoxide dismutase 1]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide	-	?
[superoxide dismutase 1]-N6-succinal-L-lysine + NAD+ + H2O	SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification	Homo sapiens	[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[superoxide dismutase 1]-N6-succinyl-L-lysine + NAD+ + H2O	-	Homo sapiens	[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?
[superoxide dismutase 1]-N6-succinyl-L-lysine + NAD+ + H2O	-	Mus musculus	[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide	-	?

Synonyms

Synonyms	Comment	Organism
SIRT5	-	Homo sapiens
SIRT5	-	Mus musculus
sirtuin 5	-	Homo sapiens
sirtuin 5	-	Mus musculus

Expression

Organism	Comment	Expression
Homo sapiens	SIRT5 expression is downregulated in human pancreatic ductal adenocarcinoma tissues. Activation of AMP-activated protein kinase (AMPK) causes SIRT5 downregulation	down
Mus musculus	SIRT5 expression is downregulated in murine pancreatic tumors	down
Homo sapiens	increased SIRT5 expression in human breast tumors is correlated with poor prognosis for patients	up

General Information

General Information	Comment	Organism
drug target	SIRT5 is a promising target in the design of activators or inhibitors that might act as therapeutics in many pathologies, including cancer, cardiovascular disorders, and neurodegeneration. Activating SIRT5 could be a promising strategy to target pancreatic ductal adenocarcinoma	Homo sapiens
malfunction	SIRT5 knockout mice displayed decreased glycolytic flux	Mus musculus
physiological function	SIRT5 is involved in different processes, including the maintenance of genomic stability, metabolism, and tumor microenvironment regulation. SIRT5 plays a dichotomous role, since it either suppresses or promotes cancer initiation or progression depending on various factors such as tissue or cell type and transformation stage. This is a consequence, at least in part, of the SIRT5-mediated regulation of ATP production and oxidative stress. ROS detoxification may be beneficial in healthy cells to avoid DNA damage and prevent tumorigenesis. On the other hand, the same mechanism protects tumor cells from apoptosis, supports cell proliferation, and may reduce the susceptibility to genotoxic chemotherapeutics	Homo sapiens
physiological function	SIRT5 regulates glucose metabolism. SIRT5 is involved in insulin sensitivity	Mus musculus