Virtual screening and further development of novel ALK inhibitors

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• 作者：Masako Okamoto^a ; ^b ; ^{okamoto@pharmadesign.co.jp"" rel=""nofollow} ; Hirotatsu Kojima^b ; ^{kojima@mol.f.u-tokyo.ac.jp"" rel=""nofollow} ; Nae Saito^b ; ^{nae-saito@mol.f.u-tokyo.ac.jp"" rel=""nofollow} ; Takayoshi Okabe^b ; ^{tokabe@mol.f.u-tokyo.ac.jp"" rel=""nofollow} ; Yoshiaki Masuda^a ; ^b ; ^{masuda@pharmadesign.co.jp"" rel=""nofollow} ; Toshio Furuya^a ; ^b ; ^{furuya@pharmadesign.co.jp"" rel=""nofollow} ; Tetsuo Nagano^b ; ^c ; ^{tlong@mol.f.u-tokyo.ac.jp"" rel=""nofollow}
• 关键词：ALK ; anaplastic lymphoma kinase ; NSCLC ; non-small-cell lung cancer ; Virtual screening ; Chemical library
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2011
• 出版时间：15 May 2011
• 年：2011
• 卷：19
• 期：10
• 页码：3086-3095
• 全文大小：2415 K

文摘

Anaplastic lymphoma kinase (ALK) has been in the spotlight in recent years as a promising new target for therapy of non-small-cell lung cancer (NSCLC). Since the identification of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene in some NSCLC patients was reported in 2007, various research groups have been seeking ALK inhibitors. Above all, crizotinib (PF-02341066) has been under clinical trial, and its therapeutic efficacy of inhibiting ALK in NSCLC has been reported. Among anticancer drugs, drug resistance appears frequently necessitating various kinds of inhibitors. We identified novel ALK inhibitors by virtual screening from the public chemical library collected by the Chemical Biology Research Initiative (CBRI) at the University of Tokyo, and inhibitors that are more potent were developed.