title: Virtual screening and further development of novel ALK inhibitors.
abstract: 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.
authors.affiliation: Drug Discovery Department, Research & Development Division, PharmaDesign, Inc., Hatchobori, Chuo-ku, Tokyo, Japan. okamoto@pharmadesign.co.jp
authors.forename: Masako
authors.initials: M
authors.lastname: Okamoto
authors.forename: Hirotatsu
authors.initials: H
authors.lastname: Kojima
authors.forename: Nae
authors.initials: N
authors.lastname: Saito
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Okabe
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Masuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Furuya
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases