7KHK

Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX9486 (bezuclastinib) in the DFG-in state

7KHK の概要

• エントリーDOI: 10.2210/pdb7khk/pdb
• 関連するPDBエントリー: 7KHG 7KHJ
• 分子名称: Mast/stem cell growth factor receptor Kit, 4,5-dimethyl-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazole-3-carboxamide (3 entities in total)
• 機能のキーワード: transferase, tyrosine-protein kinase, atp-binding, kinase-kinase inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76630.87

構造登録者

Zhang, Y. (登録日: 2020-10-21, 公開日: 2021-07-07, 最終更新日: 2023-10-18)

主引用文献

Wagner, A.J.,Severson, P.L.,Shields, A.F.,Patnaik, A.,Chugh, R.,Tinoco, G.,Wu, G.,Nespi, M.,Lin, J.,Zhang, Y.,Ewing, T.,Habets, G.,Burton, E.A.,Matusow, B.,Tsai, J.,Tsang, G.,Shellooe, R.,Carias, H.,Chan, K.,Rezaei, H.,Sanftner, L.,Marimuthu, A.,Spevak, W.,Ibrahim, P.N.,Inokuchi, K.,Alcantar, O.,Michelson, G.,Tsiatis, A.C.,Zhang, C.,Bollag, G.,Trent, J.C.,Tap, W.D.
Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors: A Phase 1b/2a Nonrandomized Clinical Trial.
Jama Oncol, 7:1343-1350, 2021

PubMed Abstract: Many cancer subtypes, including KIT-mutant gastrointestinal stromal tumors (GISTs), are driven by activating mutations in tyrosine kinases and may initially respond to kinase inhibitors but frequently relapse owing to outgrowth of heterogeneous subclones with resistance mutations. KIT inhibitors commonly used to treat GIST (eg, imatinib and sunitinib) are inactive-state (type II) inhibitors.

PubMed: 34236401
DOI: 10.1001/jamaoncol.2021.2086

実験手法

X-RAY DIFFRACTION (2.34 Å)