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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P53582 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HUVEC cell | - |
Homo sapiens | - |
NCI-H1299 cell | - |
Homo sapiens | - |
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 | Comment | Organism |
---|---|---|
MetAP1 | - |
Homo sapiens |
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 | 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 |