Discovery of 4‑Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents

• Published in: ACS medicinal chemistry letters Vol. 9; no. 11; pp. 1117 - 1122
• Main Authors: Zhang, Yong, Zhao, Yufen, Tebben, Andrew J, Sheriff, Steven, Ruzanov, Max, Fereshteh, Mark P, Fan, Yi, Lippy, Jonathan, Swanson, Jesse, Ho, Ching-Ping, Wautlet, Barri S, Rose, Anne, Parrish, Karen, Yang, Zheng, Donnell, Andrew F, Zhang, Liping, Fink, Brian E, Vite, Gregory D, Augustine-Rauch, Karen, Fargnoli, Joseph, Borzilleri, Robert M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 08.11.2018; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; TGFβ inhibitor; water-mediated protein−ligand interaction; structure-based drug design; antitumor efficacy; immuno-oncology; Selective kinase inhibitor; CELLS; METASTASIS; I-RECEPTOR KINASE; water-mediated protein-ligand interaction; CANCER; TGF beta inhibitor; SELECTIVE INHIBITOR; THERAPY; SIGNALING PATHWAY; GROWTH; LY2157299; BLOCKADE

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 TG...