Identification Back Directory [Name] GSK547[CAS] 2226735-55-1 [Synonyms] RIP1I GSK547 CPD3508 RIP1 inhibitor 547 RIP1 inhibitor GSK547 (S)-6-(4-(5-(3,5-Difluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)piperidin-1-yl)pyrimidine-4-carbonitrile 4-Pyrimidinecarbonitrile, 6-[4-[[(5S)-5-(3,5-difluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]carbonyl]-1-piperidinyl]-[Molecular Formula] C20H18F2N6O[MDL Number] MFCD32062767[MOL File] 2226735-55-1.mol [Molecular Weight] 396.39
Chemical Properties Back Directory [Boiling point ] 578.3±60.0 °C(Predicted)[density ] 1.43±0.1 g/cm3(Predicted)[storage temp. ] Store at -20°C[solubility ] DMSO:65.0(Max Conc. mg/mL);163.98(Max Conc. mM)[form ] Solid[pka] 1.93±0.28(Predicted)[color ] White to off-white
Hazard Information Back Directory [Biological Activity] GSK'547 is a highly selective and potent inhibitor of RIP1 (RIPK1) with a 400-fold increase in oral exposure compared to GSK'963 in mouse pharmacokinetic studies.[in vitro]
In vitro, treatment with GSK'547 directed bone marrow-derived macrophages to develop an immunogenic phenotype, with up-regulation of MHC-II, TNFa and IFNg expression, and decreased CD206, IL- 10 and TGFb expression. In addition, it also up-regulated STAT1 signaling and decreased STAT3, STAT5 and STAT6 signaling in bone marrow-derived macrophages. Macrophages treated with GSK'547 had stronger ability to capture antigens.
[in vivo] Mice were given GSK'547 through food, the concentration of GSK'547 in vivo was stable within 24 hours, which was higher than the IC50 value in L929 cells. GSK'547 maintained high concentrations in vivo during the 6-week administration. GSK'547 was well tolerated with no obvious pathological features. In mice with in situ pancreatic ductal adenocarcinoma, It reduced tumor burden and prolonged survival compared to control and Nec-1s-treated groups. GSK'547 prevents established tumors and liver metastases.
[target]
Company Name:
BOC Sciences
Tel:
16314854226
Website:
www.bocsci.com
Tags:2226735-55-1
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