Molecular Weight(MW): 396.39
GSK'547 is a highly selective and potent inhibitor of RIP1 exhibiting a 400-fold improvement in mouse pharmacokinetic oral exposure compared with GSK'963
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|Description||GSK'547 is a highly selective and potent inhibitor of RIP1 exhibiting a 400-fold improvement in mouse pharmacokinetic oral exposure compared with GSK'963|
GSK'547 (RIP1i) treatment in vitro directs the programming of bone marrow-derived macrophages (BMDM) toward an immunogenic phenotype, upregulating MHC-II, TNFa, and IFNg, while concomitantly reducing CD206, IL-10, and TGFb expression. Moreover, RIP1i upregulates STAT1 signaling in BMDM, which is associated with M1 programming, but reduced STAT3, STAT5, and STAT6 signaling, which are linked to M2-like macrophage differentiation. Furthermore, RIP1i-treated macrophages display enhanced ability to capture antigen.
Administration of GSK'547 (RIP1i) in mouse chow achieves in vivo steady-state concentrations above the L929 IC90 over a 24-hr period. High serum concentrations of RIP1i are sustained over a 6-week treatment course. RIP1i treatment is well tolerated without evident pathology. In mice challenged with orthotopic PDA (pancreatic ductal adenocarcinoma) tumor cells derived from KPC mice, RIP1i reduces tumor burden and extends survival cpmpared with mice treated with controls or Nec-1s. RIP1i also protects against established tumors and liver metastases.
|In vitro||DMSO||29 mg/mL (73.16 mM)|
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