| In Vitro | Necrostatin-1 (1-100 μM) inhibits the autophosphorylation of overexpressed and endogenous RIP1.It is found RIP1 is the primary cellular target responsible for the antinecroptosis activity of Necrostatin-1. Necrostatin-1 efficiently suppresses necroptotic cell death triggered by an array of stimuli in a variety of cell types. |
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| In Vivo | Necrostatin-1 (Nec-1) induces tubular bilation and affects the kinetics of the dilation of peritubular capillaries after RCM application. Upon a single intraperitoneal application of a single dose of Necrostatin-1 (1.65 mg/kg body weight, i.p.) 15 minutes before RCM, the return to baseline levels is prevented within the observation period. |
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| Animal model | Mice: 8-10 week old male C57BL/6 mice (average weight approx.23 g) are used. Mice receive intravenous application of 200 μL PBS or radiocontrast media (RCM) via the tail vein. A single dose of Z-VAD-fmk (10 mg/kg body weight) or Necrostatin-1 (1.65 mg/kg body weight) is applied intraperitoneally 15 min. before RCM-injection. Mice are harvested another 24 hours after RCM-application (48 hours after reperfusion). Blood samples are obtained from retroorbital bleeding and serum levels of urea and creatinine are determined. |
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| Formulation & Dosage | 1.65 mg/kg; i.p. |
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| References | Degterev A, et al. Nat Chem Biol, 2005, 1(2), 112-119.; J Am Soc Nephrol. 2013 Oct;24(10):1545-57. |
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