| Bioactivity | PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC50 of ~90 nM, displays inhibition of RIPK1-dependent necroptosis. PK68 powerfully ameliorates TNF-induced systemic inflammatory response syndrome, and can be used for the research of inflammatory disorders and cancer metastasis[1]. | ||||||||||||
| Invitro | PK68 has highly potent inhibition of TNF-induced necroptosis with EC50 values of 23 nM and 13 nM in human and mouse cells, respectively[1].PK68 is a highly selective inhibitor of RIPK1 kinase activity with IC50 value of 90 nM[1].PK68 (100 nM, 1 h) blocks necroptosis through the suppression of RIPK3 function or signaling upstream of RIPK3 activation[1]. Cell Viability Assay[1] Cell Line: | ||||||||||||
| In Vivo | 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[1].PK68 (1 mg/kg, i.p.) ameliorates TNF-induced systemic inflammatory response syndrome[1].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[1]. Animal Model: | ||||||||||||
| Name | PK68 | ||||||||||||
| CAS | 2173556-69-7 | ||||||||||||
| Formula | C22H24N4O3S | ||||||||||||
| Molar Mass | 424.52 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [1]. Jue Hou, et al. Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis. Cell Death Dis. 2019 Jun 24;10(7):493. |