Discovery of di-indolinone as a novel scaffold for protein tyrosine phosphatase 1B inhibitors

Hou-ling Dai; Li-xin Gao; Ying Yang; Jing-ya Li; Jia-gao Cheng; Jia Li; Ren Wen; Yan-qing Peng; Jian-bin Zheng

doi:10.1016/j.bmcl.2012.10.054

Discovery of di-indolinone as a novel scaffold for protein tyrosine phosphatase 1B inhibitors

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7440-3. doi: 10.1016/j.bmcl.2012.10.054. Epub 2012 Oct 17.

Authors

Hou-ling Dai¹, Li-xin Gao, Ying Yang, Jing-ya Li, Jia-gao Cheng, Jia Li, Ren Wen, Yan-qing Peng, Jian-bin Zheng

Affiliation

¹ Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.

PMID: 23122522
DOI: 10.1016/j.bmcl.2012.10.054

Abstract

A series of di-indolinone derivatives was designed and synthesized to optimize our lead compounds basing on molecular docking study as PTP1B inhibitors. Successive enzymatic assay identified the synthetic di-indolinone as novel PTP1B inhibitors with low micromole-ranged inhibitory activity and at least several-fold selectivity over other tested homologous PTPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Drug Discovery*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Models, Molecular
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Indoles
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1