| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
NIM811 targets mitochondrial permeability transition pore (mPTP) and cyclophilin (specifically cyclophilin A). It blocks the mitochondrial permeability transition induced by calcium and inorganic phosphate. The compound also exhibits antiviral activity against hepatitis C virus through inhibition of cyclophilin, which is essential for HCV replication. It is a dual inhibitor with both mitochondrial and antiviral targets.
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|---|---|
| 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].
NIM811 induces a concentration-dependent reduction of HCV RNA in replicon cells with an IC₅0 of 0.66 microM at 48 hours. The combination of NIM811 with alpha interferon significantly enhances anti-HCV activities without increasing cytotoxicity. It blocks the mitochondrial permeability transition induced by calcium and inorganic phosphate. The compound is a useful alternative to PKF220-384 for studying mitochondrial permeability transition in cell death. |
| ln Vivo |
By inhibiting severe mitochondrial degeneration, NIM811 improves liver function and newborn rates while also lessening liver damage and promoting regeneration [3].
In vivo, NIM811 prevents mitochondrial depolarization, attenuates liver injury, stimulates regeneration, and improves liver function and survival. By inhibiting severe mitochondrial degeneration, it lessens liver damage and promotes regeneration. The compound is orally bioavailable and has demonstrated efficacy in models of liver injury. Its ability to protect mitochondria in vivo makes it a valuable tool for studying organ protection under stress conditions. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for NIM811 typically involves measuring inhibition of cyclophilin activity using a peptidyl-prolyl cis-trans isomerase (PPIase) assay. Recombinant cyclophilin is incubated with a synthetic peptide substrate and varying concentrations of NIM811. Isomerase activity is monitored spectrophotometrically by following the cleavage of a chromogenic substrate. IC₅0 values are calculated from dose-response curves. For mitochondrial permeability transition studies, isolated mitochondria are treated with calcium and phosphate to induce pore opening, and swelling is measured spectrophotometrically.
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| Cell Assay |
For in vitro cell-based assays, HCV replicon cells are cultured and treated with NIM811 at various concentrations for 48 hours. HCV RNA levels are quantified by real-time RT-PCR to determine the inhibitory effect. Cytotoxicity is assessed using standard cell viability assays such as MTT or CellTiter-Glo. Combination studies with alpha interferon are performed to evaluate synergistic effects. Cells are maintained under standard culture conditions and experiments are typically performed in triplicate.
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| Animal Protocol |
In vivo animal studies for NIM811 typically involve mouse or rat models of liver injury or HCV infection. NIM811 is administered orally or intravenously at various doses. Liver function is assessed by measuring serum transaminase levels (ALT/AST), and liver histology is examined for signs of injury and regeneration. Survival rates are monitored in severe injury models. The compound's ability to prevent mitochondrial depolarization is evaluated using tissue samples.
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| ADME/Pharmacokinetics |
NIM811 is orally bioavailable with good systemic exposure. The molecular weight is 1202.61 with molecular formula C₆2H111N11O12. It is soluble in DMSO at 100 mg/mL (83.15 mM) and can be formulated in 10% DMSO + 90% corn oil at 5 mg/mL for in vivo administration. The compound should be stored under nitrogen at -80degC for up to 2 years or -20degC for 1 year. Further detailed PK parameters (half-life, Cmax, AUC) are available in specialized literature.
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| Toxicity/Toxicokinetics |
Toxicological data for NIM811 indicate that it is non-immunosuppressive unlike cyclosporin A, making it safer for long-term studies. Resistance to NIM811 develops through mutations in cyclophilin A that reduce inhibitor affinity. The compound is for research use only and not for human therapeutic applications. Standard preclinical toxicity profiling would be required for therapeutic development, including assessments of genotoxicity, organ toxicity, and maximum tolerated dose.
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| References |
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| Additional Infomation |
9-(N-methyl-L-isoleucine)-cyclosporine A (NIM811) has been used in trials to treat genotype 1 relapse of chronic hepatitis C. (Melle-4) cyclosporine has been found in Bacillus thuringiensis, and relevant data are available.
NIM811 is a cyclosporin A analog with molecular formula C₆2H111N11O12 and molecular weight 1202.61. It is also known as SDZ NIM811 and (Melle-4)cyclosporin. The compound is used in neuroscience and mitochondrial research. It is not approved for clinical use and is strictly for laboratory research purposes. The compound's unique biochemical profile makes it valuable for dissecting mitochondrial function and studying cell death pathways. |
| Molecular Formula |
C62H111N11O12
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|---|---|
| Molecular Weight |
1202.61124
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| Exact Mass |
1201.841
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| CAS # |
143205-42-9
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| PubChem CID |
6473876
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| Appearance |
White to off-white solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
1293.6±65.0 °C at 760 mmHg
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| Flash Point |
736.2±34.3 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.469
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| LogP |
3.35
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
85
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| Complexity |
2330
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| Defined Atom Stereocenter Count |
13
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| 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
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| InChi Key |
RPJPZDVUUKWPGT-FOIHOXPVSA-N
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| 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
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~170 mg/mL (~141.36 mM)
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|---|---|
| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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