3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.

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Sheppard GS, Wang J, Kawai M, BaMaung NY, Craig RA, Erickson SA, Lynch L, Patel J, Yang F, Searle XB, Lou P, Park C, Kim KH, Henkin J, Lesniewski R

3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.

Bioorg Med Chem Lett. 2004 Feb 23;14(4):865-8.

PubMed ID

15012983 [ View in PubMed

]

Abstract

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Methionine aminopeptidase 2	P50579	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(2s,3r)-3-Amino-2-Hydroxy-5-(Ethylsulfanyl)Pentanoyl-((S)-(-)-(1-Naphthyl)Ethyl)Amide	Methionine aminopeptidase 2	IC 50 (nM)	30	N/A	N/A	Details
N'-((2S,3R)-3-AMINO-2-HYDROXY-5-(ISOPROPYLSULFANYL)PENTANOYL)-N-3-CHLOROBENZOYL HYDRAZIDE	Methionine aminopeptidase 2	IC 50 (nM)	110	N/A	N/A	Details
N'-(2s,3r)-3-Amino-4-Cyclohexyl-2-Hydroxy-Butano-N-(4-Methylphenyl)Hydrazide	Methionine aminopeptidase 2	IC 50 (nM)	170	N/A	N/A	Details