9BHJ

MerTK in complex with small molecule 6-{1-[([1,1'-biphenyl]-4-yl)carbamoyl]azetidin-3-yl}-3-[(1-methyl-1H-pyrazol-4-yl)amino]pyrazine-2-carboxamide

これはPDB形式変換不可エントリーです。

9BHJ の概要

• エントリーDOI: 10.2210/pdb9bhj/pdb
• 分子名称: Tyrosine-protein kinase Mer, 6-{1-[([1,1'-biphenyl]-4-yl)carbamoyl]azetidin-3-yl}-3-[(1-methyl-1H-pyrazol-4-yl)amino]pyrazine-2-carboxamide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: kinase atp competitive inhibitor, transferase-inhibitor complex, 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: 37946.44

構造登録者

Jakob, C.G.,Qiu, W. (登録日: 2024-04-20, 公開日: 2024-10-09, 最終更新日: 2024-10-23)

主引用文献

Frey, R.R.,Jana, N.,Gorman, J.V.,Wang, J.,Smith, H.A.,Bromberg, K.D.,Thakur, A.,Doktor, S.Z.,Indulkar, A.S.,Jakob, C.G.,Upadhyay, A.K.,Qiu, W.,Manaves, V.,Gambino Jr., F.,Valentino, S.A.,Montgomery, D.,Zhou, Y.,Li, T.,Buchanan, F.G.,Ferguson, D.C.,Kurnick, M.D.,Kapecki, N.,Lai, A.,Michaelides, M.R.,Penning, T.D.
Discovery of Potent Azetidine-Benzoxazole MerTK Inhibitors with In Vivo Target Engagement.
J.Med.Chem., 67:17033-17052, 2024

PubMed Abstract: Inhibition of the receptor tyrosine kinase MerTK by small molecules has the potential to augment the immune response to tumors. Potent, selective inhibitors with high levels of target engagement are needed to fully evaluate the potential use of MerTK inhibitors as cancer therapeutics. We report the discovery and optimization of a series of pyrazinamide-based type 1.5 MerTK inhibitors bearing an azetidine-benzoxazole substituent. Compound potently engages the target and demonstrates single agent activity in the immune-driven MC-38 murine syngeneic tumor model.

PubMed: 39350472
DOI: 10.1021/acs.jmedchem.4c01451

実験手法

X-RAY DIFFRACTION (2.294 Å)