GSK3179106 (C007B-173581)

InformationGSK3179106 GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small molecule RET (c-RET) kinase inhibitor with a RET IC50 of 0.3 nM and is efficacious in vivo.TargetsRET (Cell-free assay) 0.3 nMIn vitroGSK3179106 has a clean genotoxic profile with no embedded genotoxicity liabilities and possesses good kinase selectivity: only 26 out of a set of >300 recombinant kinases are found to be inhibited at a 1 μM test concentration.In vivoSingle dose IV (bolus, 0.06 mg/kg) PK in male Sprague-Dawley rats of compound GSK3179106 formulated as 0.04 mg/mL in DMSO/6% HP-beta-CD = 5:95 with a pH of 7 as a clear solution shows low exposure with an AUC of 102 ng·h/mL. Oral PK is evaluated with the same dosing regimen as the in vivo colonic hypersensitivity model, seven doses of 10 mg/kg given over 3.5 days. Full gut PK measurements are also taken to help understand the PK/PD relationship--It reveals high concentrations of GSK3179106 in the colon contents, jejunum, duodenum, and ileum, over that in plasma. Specification: 0.98 Molecular Formula: C22H21F4N3O4 Molecular Weight: 467.41 PubChem CID: 78427026 Isomeric SMILES: CCOC1=CC(=O)NC=C1C2=CC(=C(C=C2)CC(=O)NC3=NOC(=C3)C(C)(C)C(F)(F)F)F Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/G414201-SCI_8c80c55e19cf50c427d186c4fc881962.pdf