Necrostatin-5 is an inhibitor of necroptosis (non-apoptotic cell death pathway) by indirect inhibition of RIP1 kinase. Necroptosis is defined as alternative active cell death pathway: Death-Domain Receptor (DRs, e.g. Fas/TNFR) mediated and caspase-inhibitor insensitive with specific morphology (nuclear condensation, organelle swelling, loss of plasma membrane integrity). The necrostatins have been discovered to inhibit this pathway by inhibition of the death domain receptor-associated adaptor kinase RIP1. Three distinct mechanisms appear to be involved: T-loop dependent inhibition by necrostatin-1; partially T-loop independent inhibition by necrostatin-3 and indirect inhibition of RIP1 by necrostatin-5, since necrostatin-5 is a potent inhibitor of immunnoprecipitated RIP1, but does not inhibit recombinant RIP1.
Molecular Weight | 383.49 |
Formula | C19H17N3O2S2 |
CAS Number | 337349-54-9 |
Solubility (25°C) | DMSO: ≥10 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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