3AOX: X-Ray Crystal Structure Of Human Anaplastic Lymphoma Kinase In Complex With Ch5424802

Citation:
Abstract
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that is constitutively activated in certain cancers, following gene alterations such as chromosomal translocation, amplification, or point mutation. Here, we identified CH5424802, a potent, selective, and orally available ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against cancers with gene alterations of ALK, such as nonsmall cell lung cancer (NSCLC) cells expressing EML4-ALK fusion and anaplastic large-cell lymphoma (ALCL) cells expressing NPM-ALK fusion in vitro and in vivo. CH5424802 inhibited ALK L1196M, which corresponds to the gatekeeper mutation conferring common resistance to kinase inhibitors, and blocked EML4-ALK L1196M-driven cell growth. Our results support the potential for clinical evaluation of CH5424802 for the treatment of patients with ALK-driven tumors.
PDB ID: 3AOXDownload
MMDB ID: 90726
PDB Deposition Date: 2010/10/8
Updated in MMDB: 2011/07
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 3AOX: monomeric; determined by author and by software (PISA)
Molecular Components in 3AOX
Label Count Molecule
Protein (1 molecule)
1
ALK Tyrosine Kinase Receptor(Gene symbol: ALK)
Molecule annotation
Chemicals (5 molecules)
1
1
2
4
* Click molecule labels to explore molecular sequence information.

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