Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.11.18 extracted from

  • Zhang, F.; Bhat, S.; Gabelli, S.B.; Chen, X.; Miller, M.S.; Nacev, B.A.; Cheng, Y.L.; Meyers, D.J.; Tenney, K.; Shim, J.S.; Crews, P.; Amzel, L.M.; Ma, D.; Liu, J.O.
    Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells (2013), J. Med. Chem., 56, 3996-4016.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure of N-terminally truncated MetAP1 in complex with inhibitor 4-[4-(4-methoxyphenyl)piperazin-1-yl]-2-(pyridin-2-yl)quinazoline and Co(II) Homo sapiens
N-terminally truncated isoform AP1 in complex with inhibitor 5-chloro-2-(5-chloropyridin-2-yl)-6-methyl-N-((R)-2-phenyl-2-(4-phenylbutylamino)ethyl)pyrimidin-4-amine. Both pyridine nitrogen N1 and pyrimidine nitrogen N1 are bound to Co3, displaying a near-perfect octahedral coordination which is completed by the nitrogen atom from the side chain of His212 and three water molecules Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
4-[4-(4-methoxyphenyl)piperazin-1-yl]-2-(pyridin-2-yl)quinazoline EC50 value in presence of Co(II) is 0.0001 mM, superior inhibitory potency and selectivity for isoform MetAP1 Homo sapiens
5-chloro-2-(5-chloropyridin-2-yl)-6-methyl-N-((R)-2-phenyl-2-(4-phenylbutylamino)ethyl)pyrimidin-4-amine compound shows 500fold specificity for isoform AP1 over isoform AP2 Homo sapiens
5-chloro-2-(5-chloropyridin-2-yl)-N-(2,4-diphenylbutyl)-6-methylpyrimidin-4-amine compound shows 3175fold specificity for isoform AP1 over isoform AP2 Homo sapiens
additional information identification of inhibitors for human methionine aminopeptidases MetAP1 and MetAP2. 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine is the minimum element for the inhibition of MetAP1, 5'-chloro is the favored substituent on the pyridine ring for the enhanced potency against MetAP1, and long C4 side chains are the essentials for higher Met AP1-selectivity Homo sapiens
N-((R)-2-(5-chloro-2-(5-chloropyridin-2-yl)-6-methylpyrimidin-4-ylamino)-1-phenylethyl)-3-phenylpropanamide compound shows 323fold specificity for isoform AP1 over isoform AP2 Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P53582
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HUVEC cell
-
Homo sapiens
-
NCI-H1299 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
14-3-3gamma protein + H2O 14-3-3gamma is a shared substrate between isoform MetAP1 and MetAP2 in HUVEC cells Homo sapiens ?
-
?
L-Met-L-Pro-4-nitroanilide + H2O
-
Homo sapiens L-Met + L-Pro-4-nitroanilide
-
?

Synonyms

Synonyms Comment Organism
MetAP1
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000063
-
22°C, pH not specified in the publication Homo sapiens 5-chloro-2-(5-chloropyridin-2-yl)-N-(2,4-diphenylbutyl)-6-methylpyrimidin-4-amine
0.000093
-
22°C, pH not specified in the publication Homo sapiens N-((R)-2-(5-chloro-2-(5-chloropyridin-2-yl)-6-methylpyrimidin-4-ylamino)-1-phenylethyl)-3-phenylpropanamide
0.0002
-
22°C, pH not specified in the publication Homo sapiens 5-chloro-2-(5-chloropyridin-2-yl)-6-methyl-N-((R)-2-phenyl-2-(4-phenylbutylamino)ethyl)pyrimidin-4-amine

General Information

General Information Comment Organism
physiological function inhibition of the enzymatic activity of isoform MetAP2 inhibitor fumagillin or siRNA mediated down-regulation of the protein level of MetAP2 both lead to strong signals of unprocessed 14-3-3gamma protein with intact initiator methionine in the immunoblot Homo sapiens