NIM811 ((Melle-4)cyclosporin) (Synonyms: (Melle-4)cyclosporin; SDZ NIM811)

NIM811 (SDZ NIM811) is a potent mitochondrial permeability transition inhibitor. Sequence: Cyclo[{Aaa}-{Abu}-{Sar}-Ile-Val-Leu-Ala-{D-Ala}-Leu-Leu-Val].

NIM811 is a potent inhibitor of HCV RNA replication in the replicon cells. NIM811 induces a concentration-dependent reduction of HCV RNA in the replicon cells with an IC50 of 0.66 μM at 48 h. Furthermore, a greater than three-log10 viral RNA reduction is achieved after treating the cells with as little as 1 μM of NIM811 for 9 days. In addition, the combination of NIM811 with alpha interferon significantly enhances anti-HCV activities without causing any increase of cytotoxicity[1]. NIM811 blocks the mitochondrial permeability transition induced by calcium and inorganic phosphate. NIM811 blocks cell killing and prevents in situ mitochondrial inner membrane permeabilization and depolarization during tumor necrosis factor-α-induced apoptosis to cultured rat hepatocytes[2].

NIM811 significantly blunts mitochondrial depolarization. Prevention of mitochondrial depolarization by NIM811 attenuates liver injury, stimulates regeneration and improves liver function and survival[3].

[1]. Ma S, et al. NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interferon. Antimicrob Agents Chemother. 2006 Sep;50(9):2976-82. [2]. Waldmeier PC, et al. Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol Pharmacol. 2002 Jul;62(1):22-9. [3]. Rehman H, et al. NIM811 prevents mitochondrial dysfunction, attenuates liver injury, and stimulates liverregeneration after massive hepatectomy. Transplantation. 2011 Feb 27;91(4):406-12.