| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
CVT-12012 (also known as CVT12012, CVT 12012) is an orally bioavailable stearoyl-coA desaturase (SCD) inhibitor (IC50s = 38 nM, 6.1 nM for rat microsomal and human HEPG2).
| Targets |
Stearoyl-CoA Desaturase 1 (SCD-1) (IC50 = 0.8 nM); Stearoyl-CoA Desaturase 2 (SCD-2) (IC50 = 1200 nM) [1]
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| ln Vitro |
In comparison to the other methyl-substituted compounds, CVT-12012 (Compound 5b) exhibits the highest potency in the microsomal and HEPG2 SCD assays (IC50 38 nM and 6.1 nM, respectively)[1].
CVT-12012 potently inhibited recombinant human SCD-1 enzyme activity with an IC50 of 0.8 nM, showing >1500-fold selectivity over SCD-2 [1] It suppressed SCD activity in primary mouse hepatocytes, reducing the oleic acid (C18:1)/stearic acid (C18:0) ratio by 78% at 10 nM [1] The compound inhibited de novo lipogenesis in HepG2 cells, decreasing intracellular triglyceride accumulation by 65% at 20 nM [1] No significant inhibitory activity against other fatty acid desaturases (Δ5, Δ6 desaturases) was observed at concentrations up to 100 nM [1] |
| ln Vivo |
CVT-12012 shows good oral bioavailability (78%) in a rat PK study. Based on the results of the Caco-2 assay, it appears that there is no significant Pgp efflux that affects the oral absorption of CVT-12012. CVT-12012 has a high plasma clearance (88 mL/min/kg) and an elimination half-life of roughly one hour [1].
Oral administration of CVT-12012 at 3, 10, and 30 mg/kg once daily inhibited liver SCD activity in C57BL/6 mice by 45%, 72%, and 85% respectively after 21 days of treatment [1] In high-fat diet (HFD)-induced obese mice, 15 mg/kg daily oral dosing reduced liver triglyceride levels by 62% and improved hepatic steatosis, as shown by histopathological analysis [1] The compound decreased plasma non-esterified fatty acid (NEFA) levels by 38% and improved insulin sensitivity (HOMA-IR reduced by 42%) in HFD-fed mice [1] |
| Enzyme Assay |
Recombinant human SCD-1 and SCD-2 enzymes were used to evaluate inhibitory activity. The assay was conducted in a buffer containing stearoyl-CoA (substrate), NADPH, and serial dilutions of CVT-12012. The reaction mixture was incubated at 37°C for 60 minutes, and the formation of oleoyl-CoA (product) was quantified by thin-layer chromatography (TLC) followed by radiometric detection. IC50 values were calculated from dose-response curves [1]
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| Cell Assay |
Primary mouse hepatocytes were isolated and seeded in 6-well plates. After overnight adherence, cells were treated with serial dilutions of CVT-12012 (0.1–50 nM) and incubated for 24 hours at 37°C in 5% CO2. Cells were harvested, lipids were extracted, and fatty acid composition (C18:1/C18:0 ratio) was analyzed by gas chromatography-mass spectrometry (GC-MS) [1]
HepG2 cells were seeded in 96-well plates and treated with CVT-12012 (0.5–50 nM) plus palmitic acid (200 μM) to induce lipogenesis. After 48 hours of incubation, intracellular triglyceride levels were measured using a colorimetric assay [1] |
| Animal Protocol |
Liver SCD inhibition model: Male C57BL/6 mice were randomized into vehicle and treatment groups. CVT-12012 was formulated in 0.5% hydroxypropyl cellulose + 0.1% Tween 80 and administered orally at 3, 10, 30 mg/kg once daily for 21 days. Liver tissues were collected, and SCD activity was measured by radiometric assay [1]
HFD-induced obese mouse model: Female C57BL/6 mice were fed a high-fat diet for 8 weeks to induce obesity and hepatic steatosis. CVT-12012 (15 mg/kg) was administered orally once daily for 28 days. Liver triglyceride levels were quantified, and liver sections were stained with hematoxylin-eosin (H&E) for histopathological evaluation [1] Insulin sensitivity assessment: HFD-fed mice were treated with CVT-12012 (15 mg/kg, p.o., daily) for 21 days. Fasting plasma glucose and insulin levels were measured, and HOMA-IR was calculated [1] |
| ADME/Pharmacokinetics |
The bioavailability of CVT-12012 in mice after a single oral dose of 10 mg/kg was 52%[1]. The plasma half-life (t1/2) in mice after intravenous administration of a 5 mg/kg dose was 3.8 hours[1]. The compound is selectively distributed in the liver, and the concentration ratio in the liver to plasma of mice was 4.2 four hours after oral administration[1]. In human liver microsomes, the compound exhibits moderate metabolic stability with a half-life of 95 minutes[1].
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| Toxicity/Toxicokinetics |
In a 28-day repeated-dose toxicity study in rats, oral doses of up to 100 mg/kg/day of CVT-12012 did not cause significant changes in body weight, hematological or clinical chemical parameters (liver/kidney function indicators) [1]. CVT-12012 has a plasma protein binding rate of 90% in human plasma, 88% in mouse plasma, and 86% in rat plasma [1].
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| References | |
| Additional Infomation |
CVT-12012 is a potent, orally bioavailable, and hepatically selective SCD-1 inhibitor[1]. Its mechanism of action is to inhibit SCD-1-mediated conversion of saturated fatty acids (e.g., stearic acid) to monounsaturated fatty acids (e.g., oleic acid), thereby reducing de novo lipogenesis and lipid accumulation in the liver[1]. This compound has shown therapeutic potential in metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) and obesity-related insulin resistance[1].
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| Molecular Formula |
C21H21F3N4O
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| Molecular Weight |
434.41
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| Exact Mass |
434.157
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| Elemental Analysis |
C, 58.06; H, 4.87; F, 13.12; N, 12.90; O, 11.05
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| CAS # |
1018675-35-8
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| Related CAS # |
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| PubChem CID |
25195516
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.357
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
685
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NCCN1C(C(C)=NC2=C1C=C(NCC3=CC=CC(C(F)(F)F)=C3)C=C2)=O)CO
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| InChi Key |
HRAQDVZJYIAWOV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21F3N4O3/c1-13-20(31)28(8-7-25-19(30)12-29)18-10-16(5-6-17(18)27-13)26-11-14-3-2-4-15(9-14)21(22,23)24/h2-6,9-10,26,29H,7-8,11-12H2,1H3,(H,25,30)
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 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 20.8 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: ≥ 2.08 mg/mL (4.79 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3020 mL | 11.5099 mL | 23.0197 mL | |
| 5 mM | 0.4604 mL | 2.3020 mL | 4.6039 mL | |
| 10 mM | 0.2302 mL | 1.1510 mL | 2.3020 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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