GSK547 (GSK'547) is a highly selective and potent inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1), inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer.
IC50&Target
RIP1
体外研究
GSK547 (0.1-100000 nM; 24 hours) pretreats L929 cells with recombinant TNFα and zVAD at various doses for 30 min, then cell death is induced with an IC50 of 32 nM after 24 hours.
GSK547 up-regulates STAT1 signaling in bone marrow-derived macrophages (BMDM).
Cell Viability Assay
Cell Line:
L929 cells (Mouse L-cells NCTC 929)
Concentration:
0.1 nM; 10 nM; 1000 nM; 100000 nM
Incubation Time:
24 hours
Result:
Reduced viability of L929 cells after co-treatment with TNFα and zVAD with an IC50 of 32 nM.
Western Blot Analysis
Cell Line:
Bone marrow-derived macrophages (BMDM)
Concentration:
Incubation Time:
30 minutes
Result:
Up-regulated STAT1 signaling in BMDM.
体内研究
GSK547 (GSK′547; RIP1i) robustly targets RIP1 in vivo. RIP1 inhibition results in immunogenic macrophage differentiation in pancreatic cancer, leading to adaptive immune activation and tumor protection for pancreatic ductal adenocarcinoma (PDA).
GSK547 (100 mg/kg/day; fed via food-based dosing; 15-50 days) reduces tumor burden and extends survival compared with mice treated with controls or Nec-1s.
Animal Model:
The wild-type (WT) mice orthotopically implanted with Pdx1;Kras;Trp53 (KPC)-derived tumor cells
Dosage:
~100 mg/kg
Administration:
Fed via food-based dosing, daily, 15-50 days
Result:
Reduced tumor burden and extended survival.
分子式
C20H18F2N6O
分子量
396.39
CAS号
2226735-55-1
运输条件
Room temperature in continental US; may vary elsewhere.