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Discovery of 4-Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents.
ACS Medicinal Chemistry Letters 2018 November 9
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 3f 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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