Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode
| Autor: | Kumari Mahasweta, Manoj Rajappa, Sangeetha Raghuramachandran, Mohammadjavad Paydar, Anirudha Lakshminarasimhan, Sujatha Rajagopalan, Anuradha Ramanathan, Murali Ramachandra, Subramanya Hosahalli, Venkateshwar Rao Gummadi, Sunil Kumar Panigrahi, Bharathi Raja Ainan, Narasimha Rao Krishnamurthy, Srinivas Nanduri, Mohammad Rais Mustafa, Pooi-Fong Wong, Chung Yeng Looi, Girish Aggunda Renukappa |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Indoles
Clinical Biochemistry Mutant Binding pocket Pharmaceutical Science Biochemistry chemistry.chemical_compound hemic and lymphatic diseases Drug Discovery Ribose medicine Humans Point Mutation Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Protein Kinase Inhibitors Molecular Biology Crizotinib Kinase Organic Chemistry Wild type Receptor Protein-Tyrosine Kinases Molecular Docking Simulation chemistry Benzyl group Molecular Medicine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 23:4911-4918 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2013.06.071 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect