6MOB

Crystal structure of KIT1 in complex with DP2976 via co-crystallization

6MOB の概要

• エントリーDOI: 10.2210/pdb6mob/pdb
• 分子名称: Mast/stem cell growth factor receptor Kit, NITRATE ION, N-{4-chloro-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl}-N'-phenylurea, ... (4 entities in total)
• 機能のキーワード: deciphera, kit1 kinase, dp2976, decode, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36665.86

構造登録者

Edwards, T.E.,Abendroth, J.,Safford, K.,Chun, L. (登録日: 2018-10-04, 公開日: 2019-07-31, 最終更新日: 2024-04-03)

主引用文献

Smith, B.D.,Kaufman, M.D.,Lu, W.P.,Gupta, A.,Leary, C.B.,Wise, S.C.,Rutkoski, T.J.,Ahn, Y.M.,Al-Ani, G.,Bulfer, S.L.,Caldwell, T.M.,Chun, L.,Ensinger, C.L.,Hood, M.M.,McKinley, A.,Patt, W.C.,Ruiz-Soto, R.,Su, Y.,Telikepalli, H.,Town, A.,Turner, B.A.,Vogeti, L.,Vogeti, S.,Yates, K.,Janku, F.,Abdul Razak, A.R.,Rosen, O.,Heinrich, M.C.,Flynn, D.L.
Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants.
Cancer Cell, 35:738-751.e9, 2019

PubMed Abstract: Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. Ripretinib is a "switch-control" kinase inhibitor that forces the activation loop (or activation "switch") into an inactive conformation. Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibitor demonstrated to broadly inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I inhibitors. Ripretinib shows efficacy in preclinical cancer models, and preliminary clinical data provide proof-of-concept that ripretinib inhibits a wide range of KIT mutants in patients with drug-resistant GISTs.

PubMed: 31085175
DOI: 10.1016/j.ccell.2019.04.006

実験手法

X-RAY DIFFRACTION (1.8 Å)