| Literature DB >> 23880539 |
Venkateshwar Rao Gummadi1, Sujatha Rajagopalan, Chung-Yeng Looi, Mohammadjavad Paydar, Girish Aggunda Renukappa, Bharathi Raja Ainan, Narasimha Rao Krishnamurthy, Sunil Kumar Panigrahi, Kumari Mahasweta, Sangeetha Raghuramachandran, Manoj Rajappa, Anuradha Ramanathan, Anirudha Lakshminarasimhan, Murali Ramachandra, Pooi-Fong Wong, Mohammad Rais Mustafa, Srinivas Nanduri, Subramanya Hosahalli.
Abstract
We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7 m and 7 n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7 k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.Entities:
Keywords: 7-Azaindole; AODVBYYJEPEEKR-UHFFFAOYSA-N; ATZJNUYRMAFPBF-UHFFFAOYSA-N; Anaplastic large cell lymphoma (ALCL); Anaplastic lymphoma kinase (ALK); Cancer; FADONZKXBUVWLH-UHFFFAOYSA-N; FPQUAATUWBOAGG-UHFFFAOYSA-N; HCWGKZMWRCORGX-UHFFFAOYSA-N; ISOJIFQFHFOCFC-UHFFFAOYSA-N; JJYRLIVLBDHFEU-UHFFFAOYSA-N; KNRKBZCJMLVHPB-UHFFFAOYSA-N; Karpas299; LKQKEJPUPWXICV-UHFFFAOYSA-N; LRWNZUVVRSBHQU-UHFFFAOYSA-N; MGARIFYNPCFMQT-UHFFFAOYSA-N; NAKSXXPCEJGLLQ-UHFFFAOYSA-N; PGSYBTKGCJXUAV-UHFFFAOYSA-N; SDWMCZUOCJDBOJ-UHFFFAOYSA-N; WIWKHKMJZYIJLG-UHFFFAOYSA-N; WXMICXPDNXUCTC-UHFFFAOYSA-N; XUQBNEPFDRSOCA-UHFFFAOYSA-N; ZHUGMFFQPPOJNL-UHFFFAOYSA-N
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Year: 2013 PMID： 23880539 DOI： 10.1016/j.bmcl.2013.06.071
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823