4NWM: Crystal structure of Bruton agammaglobulinemia tyrosine kinase complexed with BMS-809959 aka 4-tert-butyl-n-[2-me thyl-3-(6-{[4-(morpholine-4-carbonyl)phenyl]amino}-9h- purin-2-yl)phenyl]benzamide

Citation:
Abstract
Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound 20 is very selective when screened against a panel of 400 kinases and is a potent inhibitor in cellular assays of human B cell function including B-Cell proliferation and CD86 cell surface expression and exhibited in vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows that the high selectivity is gained from filling a BTK specific lipophilic pocket. However, physical and ADME properties leading to low oral exposure hindered further development.
PDB ID: 4NWMDownload
MMDB ID: 118863
PDB Deposition Date: 2013/12/6
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.03  Å
Source Organism:
Similar Structures:
Biological Unit for 4NWM: monomeric; determined by author and by software (PISA)
Molecular Components in 4NWM
Label Count Molecule
Protein (1 molecule)
1
Tyrosine-protein Kinase BTK(Gene symbol: BTK)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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