PK68

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

PK68 是一种有效的选择性 II 型受体相互作用激酶 1 (RIPK1，IC50 = 90 nM) 抑制剂。 PK68可用于治疗炎症性疾病和癌症转移的研究。

PK68 is an effective and selective inhibitor of type II receptor-interacting kinase 1 (RIPK1, IC50 = 90?nM). PK68 can be used for research on the treatment of inflammatory disorders and cancer metastasis.

PK68 has highly potent inhibition of TNF-induced necroptosis with EC50 values of 23 nM and 13 nM in human and mouse cells, respectively.PK68 is a highly selective inhibitor of RIPK1 kinase activity with IC50 value of 90 nM.PK68 (100 nM, 1 h) blocks necroptosis through the suppression of RIPK3 function or signaling upstream of RIPK3 activation.Cell Viability Assay Cell Line:Bone marrow-derived macrophages, NIH3T3-RIPK3 cells Concentration:100 nM Incubation Time:1 h Result:PK68 block cellular activation of RIPK1, RIPK3, and MLKL upon necroptotic stimuli.PK68 inhibit TNF-induced necroptosis but not RIPK3 dimerization-induced cell death in NIH3T3-RIPK3 cells.Western Blot Analysis Cell Line:HT-29 cells Concentration:100 nM Incubation Time:1 h Result:Completely abolished phosphorylation of RIPK1, RIPK3, and MLKL.Immunofluorescence Cell Line:HT-29 cells Concentration:100 nM Incubation Time:1 h Result:Prevented generation of RIPK3 puncta.

PK68 (5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days) or (2 mg/kg, i.v.; 10 mg/kg, p.o.; for 14 days) exhibits a favorable pharmacokinetic profile and no obvious toxicity in mice.PK68 (1 mg/kg, i.p.) ameliorates TNF-induced systemic inflammatory response syndrome.PK68 (5 mg/kg, i.v.) inhibits RIPK1 that results in attenuated tumor cell transmigration across the endothelial barrier and preventive suppression of tumor metastasis. Animal Model:C57BL/6 mice Dosage:5 mg/kg, 25 mg/kg Administration:5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days Result:Exhibited favorable pharmacokinetic profiles and no obvious toxicity in mice treated with a 14-day course at a dose of 25 mg/kg.Animal Model:C57BL/6 mice Dosage:1 mg/kg Administration:1 mg/kg, i.p.Result:Providedeffective protection against TNFα-induced lethal shock.Animal Model:C57BL/6 mice Dosage:5 mg/kg Administration:5 mg/kg, i.v.Result:Significantly reduced the numberof pulmonary metastasis nodules, decreased lung metastasis, decreased number of RFP-LL/2 cells, attenuated transmigrationof RFP-LL/2 cells through the endothelial cell monolayer and had no obvious influence on the proliferation rate andinvasion ability of B16-F10 or RFP-LL/2 cells without theendothelial cell monolayer in vitro.

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Others

Other Targets

HCV

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2173556-69-7

424.52

C22H24N4O3S

>98% (HPLC)

In Vitro:?DMSO : 30 mg/mL (70.67 mM)

CC(=O)Nc1nc2ccc(cc2s1)-c1cnc(C)c(NC(=O)OC2CCCCC2)c1

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(-20℃)

With Ice Pack

≥ 2 years