4FOD: Crystal structure of human anaplastic lymphoma kinase in complex with acyliminobenzimidazole inhibitor 36

Citation:
Abstract
A class of 2-acyliminobenzimidazoles has been developed as potent and selective inhibitors of anaplastic lymphoma kinase (ALK). Structure based design facilitated the rapid development of structure-activity relationships (SAR) and the optimization of kinase selectivity. Introduction of an optimally placed polar substituent was key to solving issues of metabolic stability and led to the development of potent, selective, orally bioavailable ALK inhibitors. Compound 49 achieved substantial tumor regression in an NPM-ALK driven murine tumor xenograft model when dosed qd. Compounds 36 and 49 show favorable potency and PK characteristics in preclinical species indicative of suitability for further development.
PDB ID: 4FODDownload
MMDB ID: 101265
PDB Deposition Date: 2012/6/20
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 4FOD: monomeric; determined by author and by software (PISA)
Molecular Components in 4FOD
Label Count Molecule
Protein (1 molecule)
1
ALK Tyrosine Kinase Receptor(Gene symbol: ALK)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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