TGF-β 调节策略：近期专利述评。

Strategies for TGF-beta modulation: a review of recent patents.

机构信息

Abbott Laboratories, Medicinal Chemistry, Worcester, Massachusetts 01605-2323, USA.

出版信息

Expert Opin Ther Pat. 2009 Dec;19(12):1759-69. doi: 10.1517/13543770903397400.

DOI:10.1517/13543770903397400

PMID:19939191

Abstract

BACKGROUND

TGF-beta has been identified as a key factor in the progression of various diseases, in particular cancer and fibrosis. The signaling of TGF-beta can be modulated through three distinct strategies: using antisense nucleotides that block TGF-beta mRNA (trabedersen (AP 12009)), using monoclonal antibodies to block TGF-beta isoforms (lerdelimumab, metelimumab) or using small molecule inhibitors of the TGF-beta receptor 1 (TGF-betaR1 or ALK-5).

OBJECTIVE

This review focuses on small molecules and summarizes the most recent TGF-betaR1 inhibitors reported in the patent literature.

METHODS

We searched and analyzed the patent literature claiming chemical matter for TGF-betaR1 inhibition from the 1(st) of January 2005 to the 1(st) of January 2009.

RESULTS/CONCLUSIONS: The inhibition of TGF-beta has recently been clinically validated with antisense nucleotide trabedersen. Small molecules inhibitors of TGF-betaR1 that are now in Phase I clinical trials and in preclinical stage are, therefore, of high interest and could provide a more versatile route to TGF-beta modulation through oral dosing while maintaining the same therapeutic benefits.

摘要

背景

TGF-β已被确定为多种疾病（尤其是癌症和纤维化）进展的关键因素。TGF-β信号可以通过三种不同策略进行调节：使用反义核苷酸阻断 TGF-β mRNA（trabedersen（AP 12009）），使用单克隆抗体阻断 TGF-β 同工型（lerdelimumab、metelimumab），或使用 TGF-β 受体 1（TGF-βR1 或 ALK-5）的小分子抑制剂。