6hzu

HUMAN JAK1 IN COMPLEX WITH LASW1393HUMAN JAK1 IN COMPLEX WITH LASW1393

Structural highlights 6hzu is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function JAK1_HUMAN Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor. Publication Abstract from PubMed Janus kinases (JAKs) have a key role in regulating the expression and function of relevant inflammatory cytokines involved in asthma and chronic obstructive pulmonary disease. Herein are described the design, synthesis, and pharmacological evaluation of a series of novel purinone JAK inhibitors with profiles suitable for inhaled administration. Replacement of the imidazopyridine hinge binding motif present in the initial compounds of this series with a pyridone ring resulted in the mitigation of cell cytotoxicity. Further systematic structure-activity relationship (SAR) efforts driven by structural biology studies led to the discovery of pyridone 34, a potent pan-JAK inhibitor with good selectivity, long lung retention time, low oral bioavailability, and proven efficacy in the lipopolysaccharide-induced rat model of airway inflammation by the inhaled route. Identification of 2-Imidazopyridine and 2-Aminopyridone Purinones as Potent Pan-Janus Kinase (JAK) Inhibitors for the Inhaled Treatment of Respiratory Diseases.,Bach J, Eastwood P, Gonzalez J, Gomez E, Alonso JA, Fonquerna S, Lozoya E, Orellana A, Maldonado M, Calaf E, Alberti J, Perez J, Andres A, Prats N, Carreno C, Calama E, De Alba J, Calbet M, Miralpeix M, Ramis I J Med Chem. 2019 Oct 14. doi: 10.1021/acs.jmedchem.9b00533. PMID:31609613 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Janus kinase 3D structures

spinqualitylabelsall models 6hzu, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image