Uses
Necrostatin-5 (Nec-5) is a potent necroptosis inhibitor with an EC50 value of 0.24 μM. Necrostatin-5 also is a RIP1 inhibitor. Necrostatin-5 shows cardioprotective effects[1][2][3].
Biological Activity
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.
in vivo
Necrostatin-5 (2.46 mg/kg; i.p.) shows cardioprotective effects on the isolated heart model in rats[2].
| Animal Model: | 200-300 g, male Wistar rats[2] |
| Dosage: | 2.46 mg/kg |
| Administration: | I.p.; 60 min before experiment |
| Result: | Reduced the infarction zone caused by 30-min global ischemia and 120-min reperfusion. |
IC 50
RIPK1; necroptosis: 0.24 μM (EC
50)
References
[1] Wang K, et al. Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1455-65. DOI:
10.1016/j.bmcl.2006.11.056[2] Dmitriev YV, et al. Study of cardioprotective effects of necroptosis inhibitors on isolated rat heart subjected to global ischemia-reperfusion. Bull Exp Biol Med. 2013 Jun;155(2):245-8. DOI:
10.1007/s10517-013-2124-2[3] González-Juarbe N, et al. Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia. PLoS Pathog. 2015 Dec 11;11(12):e1005337. DOI:
10.1371/journal.ppat.1005337
