NIM811 ((Melle-4)cyclosporin; SDZ NIM811) is an orally bioactive dual (bifunctional) inhibitor of mitochondrial permeability transition (mitochondrial permeability transition) and cyclophilin (cyclophilin), with strong in vitro activity against HCV (hepatitis C virus). active.

Physicochemical Properties

Molecular Formula	C62H111N11O12
Molecular Weight	1202.61124
Exact Mass	1201.841
CAS #	143205-42-9
PubChem CID	6473876
Appearance	White to off-white solid powder
Density	1.0±0.1 g/cm3
Boiling Point	1293.6±65.0 °C at 760 mmHg
Flash Point	736.2±34.3 °C
Vapour Pressure	0.0±0.6 mmHg at 25°C
Index of Refraction	1.469
LogP	3.35
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	15
Heavy Atom Count	85
Complexity	2330
Defined Atom Stereocenter Count	13
SMILES	CC[C@H]1C(=O)N(CC(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1)[C@@H]([C@H](C)C/C=C/C)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)[C@@H](C)CC)C)C
InChi Key	RPJPZDVUUKWPGT-FOIHOXPVSA-N
InChi Code	InChI=1S/C62H111N11O12/c1-25-28-29-40(15)52(75)51-56(79)65-43(27-3)58(81)67(18)33-47(74)71(22)50(39(14)26-2)55(78)66-48(37(10)11)61(84)68(19)44(30-34(4)5)54(77)63-41(16)53(76)64-42(17)57(80)69(20)45(31-35(6)7)59(82)70(21)46(32-36(8)9)60(83)72(23)49(38(12)13)62(85)73(51)24/h25,28,34-46,48-52,75H,26-27,29-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b28-25+/t39-,40+,41-,42+,43-,44-,45-,46-,48-,49-,50-,51-,52+/m0/s1
Chemical Name	(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-24-[(2S)-butan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In replicon cells, NIM811 reduces HCV RNA in a concentration-dependent manner; at 48 hours, the IC50 value is 0.66 μM. Moreover, NIM811 and α-IFN together markedly increased anti-HCV activity without raising cytotoxicity [1]. abundant with the mitochondrial permeability transition brought on by inorganic phosphate and calcium [2].
ln Vivo	By inhibiting severe mitochondrial degeneration, NIM811 improves liver function and newborn rates while also lessening liver damage and promoting regeneration [3].
References	[1]. NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha IFN. Antimicrob Agents Chemother. 2006 Sep;50(9):2976-82. [2]. Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol Pharmacol. 2002 Jul;62(1):22-9. [3]. NIM811 prevents mitochondrial dysfunction, attenuates liver injury, and stimulates liverregeneration after massive hepatectomy. Transplantation. 2011 Feb 27;91(4):406-12.
Additional Infomation	9-(N-methyl-L-isoleucine)-cyclosporin A (NIM811) has been used in trials studying the treatment of Chronic Hepatitis C Genotype-1 Relapse. (Melle-4)cyclosporin has been reported in Tolypocladium inflatum with data available.

Solubility Data

Solubility (In Vitro)

DMSO : ~170 mg/mL (~141.36 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 5 mg/mL (4.16 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 2.5 mg/mL (2.08 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.8315 mL	4.1576 mL	8.3152 mL
	5 mM	0.1663 mL	0.8315 mL	1.6630 mL
	10 mM	0.0832 mL	0.4158 mL	0.8315 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.