2. Academic Validation
  3. 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

  • J Med Chem. 2006 Jun 29;49(13):3832-49. doi: 10.1021/jm0601001.
George S Sheppard 1,  Jieyi Wang,  Megumi Kawai,  Steve D Fidanze,  Nwe Y BaMaung,  Scott A Erickson,  David M Barnes,  Jason S Tedrow,  Lawrence Kolaczkowski,  Anil Vasudevan,  David C Park,  Gary T Wang,  William J Sanders,  Robert A Mantei,  Fabio Palazzo,  Lora Tucker-Garcia,  Pingping Lou,  Qian Zhang,  Chang H Park,  Ki H Kim,  Andrew Petros,  Edward Olejniczak,  David Nettesheim,  Phillip Hajduk,  Jack Henkin,  Richard Lesniewski,  Steven K Davidsen,  Randy L Bell
Affiliations

Affiliation

  • 1 Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Department R47A, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA. george.s.sheppard@abbott.com
PMID: 16789740 DOI: 10.1021/jm0601001
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-182419
    MetAP-2抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z