| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
mitochondrial complex 1[1]
Mitochondrial Complex I (NADH dehydrogenase; NIC1). Leramistat is a potent inhibitor of this enzyme, reducing its activity and thereby decreasing ATP production and altering metabolic and immune functions. In THP-1 human monocytes, it inhibits ATP production with an IC50 of 0.63 uM. |
|---|---|
| ln Vitro |
In vitro, Leramistat inhibits ATP production in THP-1 human monocytes with an IC50 of 0.63 uM. It alters cellular metabolism and reduces the proliferation of human primary lung fibroblasts. It has moderate stability in rat hepatocytes (t1/2 = 7 min) and high stability in human hepatocytes (t1/2 = 154 min).
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| ln Vivo |
In vivo, an animal study showed that Leramistat reduced disease severity in models of atopic dermatitis, autoimmune skin diseases, and inflammatory disorders. A Phase 2b study in patients with RA demonstrated a favorable safety profile, with no new safety concerns identified. Its in vivo efficacy supports its potential for treating RA and other immune-mediated diseases.
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| Enzyme Assay |
For non-cellular assays, mitochondrial complex I activity is measured using isolated mitochondrial membranes. The enzyme is incubated with substrates (NADH and ubiquinone) and varying concentrations of Leramistat. The rate of NADH oxidation is monitored spectrophotometrically at 340 nm. IC50 values are calculated from the dose-response curves. This system can also be used to assess the ability of the compound to inhibit ATP production.
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| Cell Assay |
For cell-based assays, human primary lung fibroblasts or THP-1 monocytes are cultured and treated with Leramistat (0.1-10 uM) for 24-72 hours. Cell proliferation is assessed via MTT or BrdU incorporation assays. ATP levels are quantified using luciferase-based bioluminescence assays. The inhibition of Complex I activity in intact cells is often confirmed by measuring the oxygen consumption rate (OCR) using a Seahorse Analyzer.
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| Animal Protocol |
For animal studies, Leramistat can be administered orally or intraperitoneally to mouse models of autoimmune diseases, such as collagen-induced arthritis (CIA). In a Phase 2b clinical trial for RA, the drug was given orally and demonstrated safety and tolerability. Dosing regimens in preclinical studies were typically once or twice daily for 2-4 weeks. Efficacy is assessed by clinical scores, histopathology, and immune cell profiling.
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| ADME/Pharmacokinetics |
Leramistat has moderate stability in rat hepatocytes (t1/2 = 7 min) and high stability in human hepatocytes (t1/2 = 154 min). It can be formulated for oral administration. A Phase 1 drug-drug interaction (DDI) study (NCT06379958) was conducted to evaluate its pharmacokinetic profile in humans, with a reported half-life of 8.5 weeks.
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| Toxicity/Toxicokinetics |
In the Phase 2b clinical trial for RA, Leramistat demonstrated a favorable safety profile. The adverse event (AE) rate was similar between the leramistat and placebo groups, with most AEs being mild and resolved without treatment. No deaths were reported, and no significant changes were noted in clinical chemistry or vital signs. No new safety concerns were identified.
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| References |
[1]. Patel, et al. Preparation of N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamides and N-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)benzenesulfonamides and their therapeutic use. World Intellectual Property Organization, WO2014207445 A1 2014-12-31.
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| Additional Infomation |
Leramistat has received Orphan Drug Designation from the FDA and is being developed by Istesso. The Phase 2b study in RA (NCT06379958) was completed, with positive results showing a favorable safety profile and potential efficacy. Further studies are planned. It is currently not approved for clinical use and is intended for research purposes.
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| Molecular Formula |
C20H21CLN2O3S
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|---|---|
| Molecular Weight |
404.910342931747
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| Exact Mass |
404.096
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| CAS # |
1642602-54-7
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| PubChem CID |
86566705
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
652
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(CCC(CC1)NS(=O)(=O)C2=CC=C(C=C2)C3=C(C=C(C=C3)Cl)C#N)O
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| InChi Key |
PHOYDFRXZMNHIF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21ClN2O3S/c1-20(24)10-8-17(9-11-20)23-27(25,26)18-5-2-14(3-6-18)19-7-4-16(21)12-15(19)13-22/h2-7,12,17,23-24H,8-11H2,1H3
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| Chemical Name |
4-(4-chloro-2-cyanophenyl)-N-(4-hydroxy-4-methylcyclohexyl)benzenesulfonamide
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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: 100 mg/mL (246.97 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 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: ≥ 2.5 mg/mL (6.17 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4697 mL | 12.3484 mL | 24.6968 mL | |
| 5 mM | 0.4939 mL | 2.4697 mL | 4.9394 mL | |
| 10 mM | 0.2470 mL | 1.2348 mL | 2.4697 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05460832
Conditions:Rheumatoid ArthritisLink: https://clinicaltrials.gov/ct2/show/NCT05951296
Conditions:Idiopathic Pulmonary FibrosisLink: https://clinicaltrials.gov/ct2/show/NCT06379958
Conditions:Pharmacokinetics
Title:Safety, Tolerability and Efficacy of MBS2320 in Patients With Rheumatoid Arthritis
Status:Completed
updateDate:2019-08-14
Ctid:NCT03139136
Link: https://clinicaltrials.gov/ct2/show/NCT03139136
Conditions:Rheumatoid ArthritisLink: https://clinicaltrials.gov/ct2/show/NCT02480946
Conditions:Arthritis, RheumatoidProducts are for research use only; We do not sell to patients
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