4JOA

Crystal Structure of Human Anaplastic Lymphoma Kinase in complex with 7-azaindole based inhibitor

Summary for 4JOA

• Entry DOI: 10.2210/pdb4joa/pdb
• Descriptor: ALK tyrosine kinase receptor, 3-[1-(2,5-difluorobenzyl)-1H-pyrazol-4-yl]-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine (3 entities in total)
• Functional Keywords: anaplastic lymphoma kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: Q9UM73
• Total number of polymer chains: 1
• Total formula weight: 39031.71

Authors

Hosahalli, S.,Krishnamurthy, N.R.,Lakshminarasimhan, A. (deposition date: 2013-03-18, release date: 2013-07-17, Last modification date: 2023-11-08)

Primary citation

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, P.F.,Mustafa, M.R.,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
Bioorg.Med.Chem.Lett., 23:4911-4918, 2013

PubMed 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.

PubMed: 23880539
DOI: 10.1016/j.bmcl.2013.06.071

Experimental method

X-RAY DIFFRACTION (2.7 Å)