5QIK

TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(6-fluoropyridin-3-yl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}acetamide

Summary for 5QIK

• Entry DOI: 10.2210/pdb5qik/pdb
• Group deposition: TGFBR (G_1002052)
• Descriptor: TGF-beta receptor type-1, N-{4-[3-(6-fluoropyridin-3-yl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}acetamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: alk5, sb431542, kinase domain, transferase-transferase inhibitor complex, transferase, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 35715.02

Authors

Sheriff, S. (deposition date: 2018-08-05, release date: 2018-10-31, Last modification date: 2024-03-06)

Primary citation

Zhang, Y.,Zhao, Y.,Tebben, A.J.,Sheriff, S.,Ruzanov, M.,Fereshteh, M.P.,Fan, Y.,Lippy, J.,Swanson, J.,Ho, C.P.,Wautlet, B.S.,Rose, A.,Parrish, K.,Yang, Z.,Donnell, A.F.,Zhang, L.,Fink, B.E.,Vite, G.D.,Augustine-Rauch, K.,Fargnoli, J.,Borzilleri, R.M.
Discovery of 4-Azaindole Inhibitors of TGF beta RI as Immuno-oncology Agents.
ACS Med Chem Lett, 9:1117-1122, 2018

PubMed 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.

PubMed: 30429955
DOI: 10.1021/acsmedchemlett.8b00357

Experimental method

X-RAY DIFFRACTION (1.58 Å)