| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| Targets |
SCD1 inhibitor-3 (compound 17a) is a potent inhibitor of stearoyl-CoA desaturase-1 (SCD1).
Mouse SCD1 (liver microsomes) IC₅₀ = 7 nM Human HepG2 cellular SCD1 IC₅₀ = 103 nM Selective over D5D and D6D (no significant inhibition at 10 µM) |
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| ln Vitro |
Compound 17a potently inhibits mouse SCD1 enzyme with an IC₅₀ of 7 nM in a liver microsomal assay. In human HepG2 cell-based assay, it shows an IC₅₀ of 103 nM for SCD1 inhibition. The compound is selective against related fatty acid desaturases D5D and D6D, showing no significant inhibition at 10 µM. Metabolic stability in rat liver microsomes is 66% remaining after 30 minutes incubation. Permeability assessed in Caco-2 cells is Papp (a-b) = 12 × 10⁻⁶ cm/s and Papp (b-a) = 19 × 10⁻⁶ cm/s.
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| ln Vivo |
SCD1 inhibitor-3 (compound 17a) (5 mg/kg; oral; 4 hours) decreases plasma C16:1/C16:0 triglyceride desaturation index by 54% [1]. SCD1 inhibitor-3 (2~10 mg/kg; oral; 4 hours) can dose-responsively lower plasma triglyceride desaturation index [1].
Compound 17a reduces the plasma C16:1n7/C16:0 triglyceride desaturation index (DI) in an acute Lewis rat model in a dose-dependent manner, with an ED₅₀ of approximately 4.6 mg/kg at 4 hours post oral administration. At 5 mg/kg, it reduces plasma DI by 54%. In a 10-day repeat-dose safety study in female Sprague-Dawley rats at 100 mg/kg (∼20-fold efficacious dose), no mechanism-based adverse effects (e.g., red eye, dry skin, hair loss) or general health issues were observed. |
| Enzyme Assay |
SCD1 enzymatic activity was determined using mouse liver microsomes. The assay measures the decreased production of tritiated water released from (9,10-³H)-labeled stearoyl coenzyme A substrate mediated by SCD1. Reaction mixtures were incubated under appropriate conditions, and the release of ³H₂O was quantified as a measure of SCD1 activity. IC₅₀ values were calculated from dose-response curves of compound inhibition.
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| Cell Assay |
SCD1 cellular activity was assessed in human hepatocellular carcinoma HepG2 cells. Cells were treated with compound and incubated with ¹⁴C-stearate substrate. SCD1 activity was determined by measuring the amount of ¹⁴C-oleic acid product formed, using appropriate extraction and detection methods. IC₅₀ values were derived from inhibition curves.
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| Animal Protocol |
Animal/Disease Models: Lewis rat[1]
Doses: 5 mg/kg Route of Administration: Po; 4 hrs (hrs (hours)) Experimental Results: Plasma C16:1/C16:0 triglyceride desaturation index diminished by 54%. Animal/Disease Models: Lewis rat[1] Doses: 2~10 mg/kg Route of Administration: Po; 4 hrs (hrs (hours)) Experimental Results: There was a dose-responsive decrease in plasma triglyceride desaturation index. For acute efficacy studies, Lewis rats were used. Compound 17a was formulated in 1% carboxymethyl cellulose (low viscosity), 0.2% Tween 20, and 98.8% water, and administered orally at doses ranging from 2 to 10 mg/kg. Plasma was collected 4 hours post-dose for measurement of C16:1/C16:0 triglyceride desaturation index. For safety assessment, female Sprague-Dawley rats were dosed orally with 100 mg/kg of compound once daily for 10 consecutive days. Animals were monitored daily for general health and specific observations on eyes and skin. For pharmacokinetic studies, Lewis rats received intravenous administration (1 mg/kg) formulated in 10% DMA, 10% solutol, 50% propylene glycol, and 30% water, or oral administration (5 mg/kg) in the CMC/Tween suspension described above. Blood samples were collected at various time points for plasma concentration analysis. |
| ADME/Pharmacokinetics |
In Lewis rats, after intravenous administration of compound 17a (1 mg/kg), its clearance (Cl) was 1.1 L/h/kg, steady-state volume of distribution (Vss) was 1.2 L/kg, and terminal half-life (t₁/₂) was 1.3 h. After oral administration (5 mg/kg), Cmax was 2.3 µM, Tmax was 0.5 h, AUC₀–₂₄ h was 6.0 µM·h, terminal half-life was 4.0 h, and oral bioavailability (F) was 52%. In a 10-day safety study, at a dose of 100 mg/kg, the plasma exposure (AUC₀–₂₄ h) on day 11 was 207 µM·h, indicating an exposure more than 34 times higher than the effective exposure (AUC = 6.0 µM·h at 5 mg/kg).
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| Toxicity/Toxicokinetics |
Compound 17a, administered orally for 10 consecutive days at a dose of 100 mg/kg in female Sprague-Dawley rats, did not cause any mechanism-related adverse reactions (e.g., ocular or skin toxicity) or general health problems. The high plasma exposure at this dose (AUC = 207 µM·h) indicates a large safety margin relative to the effective exposure. The compound did not show significant inhibition of D5D or D6D at a concentration of 10 µM, indicating good selectivity and reducing the risk of off-target toxicity associated with HUFA synthesis.
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| References | |
| Additional Infomation |
Compound 17a is a pyrazolyltriazolone-based SCD1 inhibitor discovered through structure-activity relationship optimization of triazolone derivatives. It was designed to improve systemic SCD1 inhibition-related adverse reactions (such as skin and eye toxicity) by altering its physicochemical properties (reducing cLogP and increasing tPSA) while maintaining its potent enzymatic and cellular activity. Due to its potent SCD1 inhibitory activity and favorable safety profile demonstrated in preclinical models, this compound shows promise as a candidate drug for treating metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia, as well as skin conditions like acne.
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| Molecular Formula |
C19H16FN7O2
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|---|---|
| Molecular Weight |
393.37
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| Exact Mass |
393.14
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| Elemental Analysis |
C, 58.01; H, 4.10; F, 4.83; N, 24.92; O, 8.13
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| CAS # |
1282606-48-7
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| PubChem CID |
51354459
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| Appearance |
White to off-white solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
626
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FAIXKYSRYKWWGK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16FN7O2/c20-15-5-3-13(4-6-15)11-27-19(29)26(12-23-27)17-8-16(24-25-17)18(28)22-10-14-2-1-7-21-9-14/h1-9,12H,10-11H2,(H,22,28)(H,24,25)
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| Chemical Name |
3-[1-[(4-fluorophenyl)methyl]-5-oxo-1,2,4-triazol-4-yl]-N-(pyridin-3-ylmethyl)-1H-pyrazole-5-carboxamide
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| Synonyms |
SCD1 inhibitor-3; SCD-1 inhibitor-3; SCD 1 inhibitor-3;
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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) |
DMSO : ≥ 125 mg/mL (~317.77 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5421 mL | 12.7107 mL | 25.4214 mL | |
| 5 mM | 0.5084 mL | 2.5421 mL | 5.0843 mL | |
| 10 mM | 0.2542 mL | 1.2711 mL | 2.5421 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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