4Z3V

Fragment-Based Discovery of a Small Molecule Reversible Inhibitor of Bruton's Tyrosine Kinase

Summary for 4Z3V

• Entry DOI: 10.2210/pdb4z3v/pdb
• Descriptor: Tyrosine-protein kinase BTK, IMIDAZOLE, ISOPROPYL ALCOHOL, ... (6 entities in total)
• Functional Keywords: cytoplasmic tyrosine kinase, transcriptional regulation, nuclear factor-kappab, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q06187
• Total number of polymer chains: 1
• Total formula weight: 33269.17

Authors

Dougan, D.R. (deposition date: 2015-03-31, release date: 2015-07-01, Last modification date: 2023-09-27)

Primary citation

Smith, C.R.,Dougan, D.R.,Komandla, M.,Kanouni, T.,Knight, B.,Lawson, J.D.,Sabat, M.,Taylor, E.R.,Vu, P.,Wyrick, C.
Fragment-Based Discovery of a Small Molecule Inhibitor of Bruton's Tyrosine Kinase.
J.Med.Chem., 58:5437-5444, 2015

PubMed Abstract: The discovery and optimization of a series of 4-aminocinnoline-3-carboxamide inhibitors of Bruton's tyrosine kinase are reported. A fragment-based screening approach incorporating X-ray co-crystallography was used to identify a cinnoline fragment and characterize its binding mode in the ATP binding site of Btk. Optimization of the fragment hit resulted in the identification of a lead compound which reduced paw swelling in a dose- and exposure-dependent fashion in a rat model of collagen-induced arthritis.

PubMed: 26087137
DOI: 10.1021/acs.jmedchem.5b00734

Experimental method

X-RAY DIFFRACTION (1.6 Å)