RIP1 inhibitor GSK547

Cas No.:	2226735-55-1
Chemical Name:	(S)-6-(4-(5-(3,5-difluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)piperidin-1-yl)pyrimidine-4-carbonitrile
Synonyms:	RIP1i,GSK547,GSK-547,GSK 547
SMILES:	C1=NC(N2CCC(C(N3[C@@H](C4=CC(F)=CC(F)=C4)CC=N3)=O)CC2)=CC(C#N)=N1
Formula:	C20H18F2N6O
M.Wt:	396.402
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	GSK547, a highly selective and potent RIP1 inhibitor, inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer[1].
In Vivo:	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)[1]. 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[1]. Animal Model: The wild-type (WT) mice orthotopically implanted with Pdx1Cre;KrasG12D;Trp53R172H (KPC)-derived tumor cells[1] Dosage: ~100 mg/kg Administration: Fed via food-based dosing, daily, 15-50 days Result: Reduced tumor burden and extended survival.
In Vitro:	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[1]. GSK547 up-regulates STAT1 signaling in bone marrow-derived macrophages (BMDM)[1]. Cell Viability Assay[1] 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[1] Cell Line: Bone marrow-derived macrophages (BMDM) Concentration: Incubation Time: 30 minutes Result: Up-regulated STAT1 signaling in BMDM.