Discovery of 4-Azaindole Inhibitors of TGFβRI As Immuno-oncology Agents

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Nov 16

PMID 30429955

Citations 7

Authors

Yong Zhang

Yufen Zhao

Andrew J Tebben

Steven Sheriff

Max Ruzanov

Mark P Fereshteh

Yi Fan

Jonathan Lippy

Jesse Swanson

Ching-Ping Ho

Barri S Wautlet

Anne Rose

Karen Parrish

Zheng Yang

Andrew F Donnell

Liping Zhang

Brian E Fink

Gregory D Vite

Karen Augustine-Rauch

Joseph Fargnoli

Robert M Borzilleri

Affiliations

Soon will be listed here.

Abstract

The multifunctional cytokine TGFβ plays a central role in regulating antitumor immunity. It has been postulated that inhibition of TGFβ signaling in concert with checkpoint blockade will provide improved and durable immune response against tumors. Herein, we describe a novel series of 4-azaindole TGFβ receptor kinase inhibitors with excellent selectivity for TGFβ receptor 1 kinase. The combination of compound and an antimouse-PD-1 antibody demonstrated significantly improved antitumor efficacy compared to either treatment alone in a murine tumor model.

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