5FBO: BTK-inhibitor co-structure

Citation:
Abstract
Bruton's tyrosine kinase (BTK) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) pathway. It has become an attractive kinase target for selective B cell inhibition and for the treatment of B cell related diseases. We report a series of compounds based on 8-amino-imidazo[1,5-a]pyrazine that are potent reversible BTK inhibitors with excellent kinase selectivity. Selectivity is achieved through specific interactions of the ligand with the kinase hinge and driven by aminopyridine hydrogen bondings with Ser538 and Asp539, and by hydrophobic interaction of trifluoropyridine in the back pocket. These interactions are evident in the X-ray crystal structure of the lead compounds 1 and 3 in the complex with the BTK enzyme. Our lead compounds show desirable PK profiles and efficacy in the preclinical rat collagen induced arthritis model.
PDB ID: 5FBODownload
MMDB ID: 137722
PDB Deposition Date: 2015/12/14
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.894  Å
Source Organism:
Similar Structures:
Biological Unit for 5FBO: monomeric; determined by author and by software (PISA)
Molecular Components in 5FBO
Label Count Molecule
Protein (1 molecule)
1
Tyrosine-protein Kinase BTK(Gene symbol: BTK)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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