| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
SMN protein (survival motor neuron protein) ubiquitination. NNMT (nicotinamide N-methyltransferase).
|
|---|---|
| ln Vitro |
ML372 inhibits survival motor neuron (SMN) protein ubiquitination, increasing SMN protein stability without affecting mRNA expression. The compound improves spinal muscular atrophy (SMA) in mice. It is brain penetrant and has reasonable exposure and half-life in vivo. ML372 is also reported to inhibit nicotinamide N-methyltransferase (NNMT), suggesting potential applications in modulating metabolic pathways and studying disorders such as obesity, type 2 diabetes, and certain cancers.
|
| ln Vivo |
ML372 improves spinal muscular atrophy (SMA) in mice. The compound is brain penetrant and has reasonable exposure and half-life in vivo. By inhibiting NNMT, ML372 has shown potential in modulating metabolic pathways, making it a valuable tool for studying disorders such as obesity, type 2 diabetes, and certain cancers. The compound's ability to increase SMN protein stability makes it a promising therapeutic candidate for SMA.
|
| Enzyme Assay |
The in vitro enzyme assay for NNMT inhibition uses recombinant human NNMT enzyme and its substrate, nicotinamide. ML372 is incubated with NNMT, nicotinamide, and S-adenosylmethionine (SAM) as the methyl donor at varying concentrations (typically 0.1 nM to 100 µM) at 37°C for 30-60 minutes. The product (1-methylnicotinamide) is quantified by HPLC or LC-MS/MS. The IC50 is calculated from dose-response curves. For SMN protein stabilization assays, cells are treated with ML372 and SMN protein levels are measured by Western blot.
|
| Cell Assay |
In vitro cellular assays are performed using SMA patient-derived fibroblasts or neuronal cell lines. Cells are treated with ML372 at concentrations ranging from 0.01 to 100 µM for 24-72 hours. SMN protein levels are measured by Western blot or ELISA. SMN mRNA levels are measured by qRT-PCR to confirm that the compound does not affect mRNA expression. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. For NNMT inhibition studies, metabolic flux analysis is performed to assess changes in nicotinamide metabolism.
|
| Animal Protocol |
In vivo efficacy is evaluated in mouse models of spinal muscular atrophy (SMA). SMA mice are administered ML372 orally or intraperitoneally at various doses (e.g., 10-50 mg/kg) on a scheduled basis. Motor function is assessed using rotarod, grip strength, and open field tests. Survival is monitored as a primary endpoint. SMN protein levels are measured in spinal cord and brain tissue by Western blot. Brain penetration is confirmed by measuring drug levels in brain tissue. For metabolic studies, body weight, food intake, and metabolic parameters are measured.
|
| ADME/Pharmacokinetics |
ML372 has a molecular weight of 360.43 g/mol and molecular formula C18H20N2O4S. It is brain penetrant and has reasonable exposure and half-life in vivo. The compound is soluble in DMSO and should be stored as a powder at -20°C. Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and brain penetration have been characterized in preclinical studies. The compound is typically formulated for oral or intraperitoneal administration.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for ML372. As a research compound, it is not intended for human use and has not undergone formal toxicological evaluation. Standard preclinical safety assessments would typically include selectivity profiling against a panel of targets to assess off-target effects, hERG channel inhibition for cardiac safety, and CYP450 enzyme inhibition for drug-drug interaction potential. The compound is supplied as a solid and should be stored desiccated at -20°C.
|
| Additional Infomation |
ML372 is a research-grade SMN protein stabilizer and NNMT inhibitor. It is not approved for clinical use. The compound improves spinal muscular atrophy (SMA) in mice and is brain penetrant. ML372 is also reported to inhibit NNMT, suggesting additional applications in metabolic and cancer research. It is supplied as a solid with high purity and should be stored desiccated at -20°C.
|
| Molecular Formula |
C18H20N2O4S
|
|---|---|
| Molecular Weight |
360.427403450012
|
| Exact Mass |
360.114
|
| CAS # |
1331745-61-9
|
| PubChem CID |
46907666
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
25
|
| Complexity |
472
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1COC2=C(C=C(C=C2)C3=CN=C(S3)N4CCC(CC4)C(=O)O)OC1
|
| InChi Key |
HAVNRFQWAXTDTI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H20N2O4S/c21-17(22)12-4-6-20(7-5-12)18-19-11-16(25-18)13-2-3-14-15(10-13)24-9-1-8-23-14/h2-3,10-12H,1,4-9H2,(H,21,22)
|
| Chemical Name |
1-[5-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid
|
| Synonyms |
ML 372; ML-372; ML372
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~92.47 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.94 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 | 2.7745 mL | 13.8723 mL | 27.7446 mL | |
| 5 mM | 0.5549 mL | 2.7745 mL | 5.5489 mL | |
| 10 mM | 0.2774 mL | 1.3872 mL | 2.7745 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
