4ANL

Structure of G1269A Mutant Anaplastic Lymphoma Kinase

4ANL の概要

• エントリーDOI: 10.2210/pdb4anl/pdb
• 関連するPDBエントリー: 4ANQ 4ANS 4AOI
• 分子名称: ALK TYROSINE KINASE RECEPTOR (2 entities in total)
• 機能のキーワード: transferase, crizotinib
• 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: 38610.15

構造登録者

McTigue, M.,Deng, Y.,Liu, W.,Brooun, A. (登録日: 2012-03-20, 公開日: 2013-03-27, 最終更新日: 2023-12-20)

主引用文献

Huang, Q.,Johnson, T.W.,Bailey, S.,Brooun, A.,Bunker, K.D.,Burke, B.J.,Collins, M.R.,Cook, A.S.,Cui, J.J.,Dack, K.N.,Deal, J.G.,Deng, Y.,Dinh, D.,Engstrom, L.D.,He, M.,Hoffman, J.,Hoffman, R.L.,Johnson, P.S.,Kania, R.S.,Lam, H.,Lam, J.L.,Le, P.T.,Li, Q.,Lingardo, L.,Liu, W.,Lu, M.W.,Mctigue, M.,Palmer, C.L.,Richardson, P.F.,Sach, N.W.,Shen, H.,Smeal, T.,Smith, G.L.,Stewart, A.E.,Timofeevski, S.,Tsaparikos, K.,Wang, H.,Zhu, H.,Zhu, J.,Zou, H.Y.,Edwards, M.P.
Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib.
J.Med.Chem., 57:1170-, 2014

PubMed Abstract: Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e, which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclinical pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

PubMed: 24432909
DOI: 10.1021/JM401805H

実験手法

X-RAY DIFFRACTION (1.7 Å)