GSK046 (C09-0902-112)

InformationGSK046 GSK046 (iBET-BD2) is a selective and orally active inhibitor of BET (bromodomain and extraterminal domain) with IC50 of 264 nM, 98 nM, 49 nM and 214 nM for BRD2 BD2 , BRD3 BD2 , BRD4 BD2 and BRDT BD2 , respectively. GSK046 exhibits immunomodulatory activity.TargetsBRD4BD2 (Cell-free assay); BRD3BD2 (Cell-free assay); BRDTBD2 (Cell-free assay); BRD2BD2 (Cell-free assay) 49 nM; 98 nM; 214 nM; 264 nMIn vitroGSK046 shows an excellent level of selectivity for the BET family with no measurable activity for non-BET bromodomains. GSK046 is tested in an LPS-stimulated peripheral blood mononuclear cell (PBMC) cellular assay. After stimulation, these immune cells release a range of cytokines and chemokines, including monocyte chemoattractant protein 1 (MCP-1/CCL2). GSK046 also inhibits MCP-1 production (pIC50 = 7.5) with a minimal drop-off from the biochemical BRD4 BD2 potency observed.In vivoGSK046 has suitable physicochemical and pharmacokinetic properties to be utilized and it has also been demonstrated that a highly selective BD2 inhibitor retains the ability to potently inhibit MCP-1 cytokine release in a cellular and whole blood context. GSK046 proves useful for further biological profiling. GSK046 is efficacious in a broad range of inflammatory pathologies and selective BD2 inhibition may be a useful new therapeutic strategy for immunoinflammatory diseases.Cell Research(from reference)Cell lines：PBMCs, hepatocytes Concentrations：0.5 μM Incubation Time：5 min, 10 min, 20 min, 40 min, 60 min, 120 min. Specification: 0.99 Molecular Formula: C23H27FN2O4 Molecular Weight: 414.47 PubChem CID: 146018690 Isomeric SMILES: C[C@@H](C1=CC=CC=C1)OC2=C(C(=CC(=C2)C(=O)NC3CCC(CC3)O)F)NC(=O)C Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/G414457-SCI_9ea44bdda9a5a1f83bcf55bc7859a7ed.pdf