当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.

Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.

Abstract：

:Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Sheppard GS,Wang J,Kawai M,Fidanze SD,BaMaung NY,Erickson SA,Barnes DM,Tedrow JS,Kolaczkowski L,Vasudevan A,Park DC,Wang GT,Sanders WJ,Mantei RA,Palazzo F,Tucker-Garcia L,Lou P,Zhang Q,Park CH,Kim KH,Petros A,Ol

doi

10.1021/jm0601001

subject

Has Abstract

pub_date

2006-06-29 00:00:00

pages

3832-49

issue

13

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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