| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg | |||
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| Other Sizes |
| Targets |
MF-438 targets stearoyl-CoA desaturase 1 (SCD1). [1]
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|---|---|
| ln Vitro |
MF-438 does not inhibit CYP3A4 or CYP2D6 at concentrations up to 30 μM. [1]
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| ln Vivo |
In mouse models, MF-438 has an ED50 of 1 to 3 mg/kg [1].
In a mouse liver pharmacodynamic (PD) model measuring SCD inhibition, MF-438 exhibited an ED50 between 1 and 3 mg/kg. The assay involved oral administration of the compound followed by intravenous injection of a 14C-labeled stearic acid tracer; inhibition of SCD activity was determined by comparing the conversion of 14C-stearic acid to 14C-oleic acid in treated animals versus vehicle control. [1] |
| Animal Protocol |
Mouse liver PD assay: Mice on a high-carbohydrate diet received MF-438 orally (PO). One hour later, a 14C-labeled stearic acid tracer was administered intravenously (IV). After an additional 2 hours, mouse livers were harvested and analyzed for lipid content. SCD inhibition was assessed by the conversion of 14C-stearic acid to 14C-oleic acid. [1]
- Chronic dosing toxicity study: Diet-induced obese (DIO) mice were dosed once daily with MF-438 at 5 mg/kg. Adverse effects were observed after approximately one week. Similar adverse effects were observed in obese diabetic Zucker rats. The effects were reversible upon cessation of treatment. [1] |
| ADME/Pharmacokinetics |
Oral bioavailability of MF-438 was 73% in mice and 38% in rats.
- Half-lives (t1/2) were 6.4 hours in mice and 6.0 hours in rats. - A circulating metabolite resulting from oxidation of the methyl group on the thiadiazole ring to the hydroxymethyl derivative (10g) was observed in both species at all time points, present at approximately 10% of the parent compound concentration. [1] |
| Toxicity/Toxicokinetics |
MF-438 did not inhibit CYP3A4 or CYP2D6 at concentrations up to 30 μM.
- After approximately one week of once-daily dosing at 5 mg/kg in DIO mice, symptoms of alopecia and partial eye closure began to appear. The severity and time of onset were dose-dependent. - Similar adverse effects were observed in obese diabetic Zucker rats. - These adverse effects were reversible upon cessation of treatment. [1] |
| References | |
| Additional Infomation |
MF-438 is a potent SCD1 inhibitor developed as a tool compound for in vivo assessment of SCD inhibition in models of metabolic disorders such as obesity, fatty liver disease, type 2 diabetes, and atherosclerosis. It was identified from a thiadiazole-pyridazine series, addressing metabolic stability and CYP inhibition issues of earlier amide- and imidazole-based inhibitors. The long half-lives in rodents make it suitable for once-daily dosing. [1]
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| Molecular Formula |
C19H18F3N5OS
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|---|---|
| Molecular Weight |
421.439332485199
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| Exact Mass |
421.118
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| CAS # |
921605-87-0
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| PubChem CID |
16042458
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| Appearance |
Light yellow to orange solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
535
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC(C1C(OC2CCN(C3C=CC(C4SC(C)=NN=4)=NN=3)CC2)=CC=CC=1)(F)F
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| InChi Key |
NVUJDKDVOZVALT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H18F3N5OS/c1-12-23-26-18(29-12)15-6-7-17(25-24-15)27-10-8-13(9-11-27)28-16-5-3-2-4-14(16)19(20,21)22/h2-7,13H,8-11H2,1H3
|
| Chemical Name |
2-methyl-5-(6-(4-(2-(trifluoromethyl)phenoxy)piperidin-1-yl)pyridazin-3-yl)-1,3,4-thiadiazole
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| Synonyms |
MF 438 MF438MF-438
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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 |
| 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) |
DMF : 50 mg/mL (~118.64 mM)
DMSO : ~25 mg/mL (~59.32 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.55 mg/mL (10.80 mM) (saturation unknown) in 10% DMF 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (5.93 mM) (saturation unknown) in 10% DMF 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (1.97 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. Solubility in Formulation 4: ≥ 0.83 mg/mL (1.97 mM) 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 8.3 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 5: 10% DMSO + 90% Corn Oil |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3728 mL | 11.8641 mL | 23.7282 mL | |
| 5 mM | 0.4746 mL | 2.3728 mL | 4.7456 mL | |
| 10 mM | 0.2373 mL | 1.1864 mL | 2.3728 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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