GSK547

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK547 (RIP1i, GSK 547) 是一种高度选择性且有效的 RIP1 激酶抑制剂，可在体内强力靶向 RIP1。

GSK547 (RIP1i, GSK 547) is a highly selective and potent inhibitor of RIP1 kinase that robustly targets RIP1 in vivo; exhibited a 400-fold improvement in mouse pharmacokinetic oral exposure compared with GSK'963; reprogrammed TAMs toward an MHCIIhiTNFα+IFNγ+ immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human Pancreatic ductal adenocarcinoma (PDA).

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.

Animal Model:The wild-type (WT) mice orthotopically implanted with Pdx1Cre;KrasG12D;Trp53R172H (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.

RIP1i | GSK 547 | GSK-547

Apoptosis

RIP kinase

RIP kinase

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2226735-55-1

396.402

C20H18F2N6O

>98% (HPLC)

DMSO : ≥ 125 mg/mL 315.35 mM

N#CC1=NC=NC(N2CCC(C(N3N=CC[C@H]3C4=CC(F)=CC(F)=C4)=O)CC2)=C1

(S)-6-(4-(5-(3,5-difluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)piperidin-1-yl)pyrimidine-4-carbonitrile

(-20℃)

With Ice Pack

≥ 2 years