Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode
We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7h, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) revealed a unique binding mode with the benzyl group occupyin...
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2013
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| Online Access: | http://eprints.um.edu.my/8532/1/Gummadi-2013-Discovery_of_7-azain.pdf http://eprints.um.edu.my/8532/ http://www.sciencedirect.com/science/article/pii/S0960894X13008044 |
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| author | Gummadi, V.R. Rajagopalan, S. Looi, C.Y. Paydar, M. Renukappa, G.A. Ainan, B.R. Krishnamurthy, N.R. Panigrahi, S.K. Mahasweta, K. Raghuramachandran, S. Rajappa, M. Ramanathan, A. Lakshminarasimhan, A. Ramachandra, M. Wong, Pooi Fong Mustafa, Mohd Rais Nanduri, S. Hosahalli, S. |
| author_facet | Gummadi, V.R. Rajagopalan, S. Looi, C.Y. Paydar, M. Renukappa, G.A. Ainan, B.R. Krishnamurthy, N.R. Panigrahi, S.K. Mahasweta, K. Raghuramachandran, S. Rajappa, M. Ramanathan, A. Lakshminarasimhan, A. Ramachandra, M. Wong, Pooi Fong Mustafa, Mohd Rais Nanduri, S. Hosahalli, S. |
| author_sort | Gummadi, V.R. |
| building | UM Library |
| collection | Institutional Repository |
| content_provider | Universiti Malaya |
| content_source | UM Research Repository |
| continent | Asia |
| country | Malaysia |
| description | We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7h, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) 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. (C) 2013 Elsevier Ltd. All rights reserved. |
| format | Article |
| id | my.um.eprints-8532 |
| institution | Universiti Malaya |
| language | en |
| publishDate | 2013 |
| record_format | eprints |
| spelling | my.um.eprints-85322019-12-18T06:43:43Z http://eprints.um.edu.my/8532/ Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode Gummadi, V.R. Rajagopalan, S. Looi, C.Y. Paydar, M. Renukappa, G.A. Ainan, B.R. Krishnamurthy, N.R. Panigrahi, S.K. Mahasweta, K. Raghuramachandran, S. Rajappa, M. Ramanathan, A. Lakshminarasimhan, A. Ramachandra, M. Wong, Pooi Fong Mustafa, Mohd Rais Nanduri, S. Hosahalli, S. R Medicine We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7h, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) 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. (C) 2013 Elsevier Ltd. All rights reserved. 2013 Article PeerReviewed application/pdf en http://eprints.um.edu.my/8532/1/Gummadi-2013-Discovery_of_7-azain.pdf Gummadi, V.R. and Rajagopalan, S. and Looi, C.Y. and Paydar, M. and Renukappa, G.A. and Ainan, B.R. and Krishnamurthy, N.R. and Panigrahi, S.K. and Mahasweta, K. and Raghuramachandran, S. and Rajappa, M. and Ramanathan, A. and Lakshminarasimhan, A. and Ramachandra, M. and Wong, Pooi Fong and Mustafa, Mohd Rais and Nanduri, S. and Hosahalli, S. (2013) Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode. Bioorganic & Medicinal Chemistry Letters, 23 (17). pp. 4911-4918. ISSN 0960-894X, DOI https://doi.org/10.1016/j.bmcl.2013.06.071 <https://doi.org/10.1016/j.bmcl.2013.06.071>. http://www.sciencedirect.com/science/article/pii/S0960894X13008044 10.1016/j.bmcl.2013.06.071 |
| spellingShingle | R Medicine Gummadi, V.R. Rajagopalan, S. Looi, C.Y. Paydar, M. Renukappa, G.A. Ainan, B.R. Krishnamurthy, N.R. Panigrahi, S.K. Mahasweta, K. Raghuramachandran, S. Rajappa, M. Ramanathan, A. Lakshminarasimhan, A. Ramachandra, M. Wong, Pooi Fong Mustafa, Mohd Rais Nanduri, S. Hosahalli, S. Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode |
| title | Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode |
| title_full | Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode |
| title_fullStr | Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode |
| title_full_unstemmed | Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode |
| title_short | Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode |
| title_sort | discovery of 7-azaindole based anaplastic lymphoma kinase (alk) inhibitors: wild type and mutant (l1196m) active compounds with unique binding mode |
| topic | R Medicine |
| url | http://eprints.um.edu.my/8532/1/Gummadi-2013-Discovery_of_7-azain.pdf http://eprints.um.edu.my/8532/ http://www.sciencedirect.com/science/article/pii/S0960894X13008044 |
| url_provider | http://eprints.um.edu.my/ |