5QIM

TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(5-METHOXYPYRIDIN-2-YL)-1H-PYRROLO[3,2-B] PYRIDIN-2-YL]PYRIDIN-2-YL}ACETAMIDE

5QIM の概要

• エントリーDOI: 10.2210/pdb5qim/pdb
• Group deposition: TGFBR (G_1002052)
• 分子名称: TGF-beta receptor type-1, N-{4-[3-(5-methoxypyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: alk5, sb431542, kinase domain, transferase-transferase inhibitor complex, transferase, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35390.67

構造登録者

Sheriff, S. (登録日: 2018-08-05, 公開日: 2018-10-31, 最終更新日: 2026-02-18)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.75 Å)