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Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.

Abstract：

:Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with <10nM potency, excellent selectivity, and favorable in vitro safety profiles.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Cheruvallath Z,Tang M,McBride C,Komandla M,Miura J,Ton-Nu T,Erikson P,Feng J,Farrell P,Lawson JD,Vanderpool D,Wu Y,Dougan DR,Plonowski A,Holub C,Larson C

doi

10.1016/j.bmcl.2016.04.073

subject

Has Abstract

pub_date

2016-06-15 00:00:00

pages

2774-2778

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30449-8

journal_volume

26

pub_type

杂志文章

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