Abstract

A small-molecule Stat3 dimerization inhibitor, S3I-M2001, is described and the dynamics of intracellular processing of activated Stat3 within the context of the biochemical and biological effects of the Stat3 chemical probe inhibitor are elucidated. S3I-M2001 is a newly-identified oxazole-based peptidomimetic of the Stat3 Src Homology (SH) 2 domain-binding phosphotyrosine peptide that selectively disrupts active Stat3:Stat3 dimers. Stat3-dependent malignant transformation, survival, and migration and invasion of mouse and human cancer cells harboring persistently-activated Stat3 were inhibited by S3I-M2001. S3I-M2001 inhibited Stat3-dependent transcriptional regulation of tumor survival genes, such as Bcl-xL. The disclosed compound is useful as a new potential treatment for certain cancers.

Document Type

Patent

Patent Number

US 8,609,639

Application Serial Number

12/517,453

Issue Date

12-17-2013

Current Assignee

Joint Assignment w/UCFRF: Yale University

Assignee at Issuance

Joint Assignment w/UCFRF: Yale University

College

Burnett School of Biomedical Sciences

Department

Biomolecular Science Center

Allowance Date

8-7-2013

Filing Date

6-3-2009

Assignee at Filing

Joint Assignment w/UCFRF: Yale University

Filing Type

National Filing Record

Donated

no

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