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Purity: ≥98%
GSK1940029 (also known as SCD Inhibitor 1) is a SCD Inhibitor that has the potential as a topical treatment for acne. Acyl desaturase enzymes catalyze the formation of double bonds in fatty acids derived from either dietary sources or de novo synthesis in the liver. Mammals synthesise at least three fatty acid desaturases of differing chain length that specifically catalyze the addition of double bonds at the delta-9, delta-6, and delta-5 positions. Stearoyl-CoA desaturases (SCDs) introduce a double bond in the C9-C10 position of saturated fatty acids. The preferred substrates for the enzymes are palmitoyl-CoA (16:0) and stearoyl-CoA (18:0), which are converted to palmitoleoyl-CoA (16:1 ) and oleoyl-CoA (18:1 ), respectively. The resulting mono-unsaturated fatty acids may then be employed in the preparation of phospholipids, triglycerides, and cholesteryl esters, in vivo.
| Targets |
Stearoyl-CoA desaturase (SCD, including SCD1 and SCD5) (IC50 for human SCD1 enzyme activity: 0.03 μM; IC50 for mouse SCD1 enzyme activity: 0.05 μM) [1]
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| ln Vitro |
Stearoyl-coenzyme desaturase (SCD) inhibitor GSK1940029 (SCD Inhibitor 1) is a medication that can be used to treat and/or prevent a variety of diseases, including those that are mediated by SCD enzymes, such as those linked to elevated blood lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome, skin diseases like acne, diseases or conditions related to cancer, and the management of symptoms linked to the synthesis of amyloid plaque-forming Aβ42 peptide (such as Alzheimer's disease) [1].
1. Inhibition of SCD enzyme activity: GSK1940029 potently and selectively inhibits the catalytic activity of recombinant human and mouse SCD1. The IC50 values are 0.03 μM (human) and 0.05 μM (mouse), as measured by a fatty acid desaturation assay. The compound shows no significant inhibition of other desaturases (e.g., Δ6-desaturase, Δ5-desaturase) at concentrations up to 10 μM [1] 2. Suppression of cellular monounsaturated fatty acid (MUFA) synthesis: In human hepatoma HepG2 cells and mouse 3T3-L1 adipocytes, GSK1940029 dose-dependently inhibits SCD-mediated conversion of stearic acid (C18:0) to oleic acid (C18:1n9). At 0.1 μM, the drug reduces C18:1n9 production by ~70% in HepG2 cells and ~65% in 3T3-L1 cells, without affecting cell viability (viability >90% at 1 μM) [1] 3. Inhibition of cancer cell proliferation: In SCD-dependent cancer cell lines (e.g., MCF-7 breast cancer cells, A549 lung cancer cells), GSK1940029 inhibits cell proliferation with EC50 values of 0.08 μM (MCF-7) and 0.12 μM (A549). Flow cytometry analysis shows cell cycle arrest at G0/G1 phase, accompanied by reduced expression of cyclin D1 [1] |
| ln Vivo |
1. Reduction of hepatic SCD activity in mice: C57BL/6 mice were administered GSK1940029 orally at 10 mg/kg, 30 mg/kg, or 100 mg/kg once daily for 7 days. Hepatic SCD1 enzyme activity was dose-dependently inhibited, with a maximum inhibition rate of ~85% at 100 mg/kg. Hepatic oleic acid (C18:1n9) levels were reduced by ~60% at the highest dose, while stearic acid (C18:0) levels increased by ~45% [1]
2. Attenuation of diet-induced obesity in mice: High-fat diet (HFD)-fed C57BL/6 mice were treated with GSK1940029 (30 mg/kg, oral, daily) for 4 weeks. Compared to vehicle controls, treated mice showed a ~20% reduction in body weight gain, reduced epididymal fat pad weight (~30% decrease), and lower hepatic triglyceride levels (~40% decrease). No significant changes in food intake were observed [1] 3. Improvement of glucose tolerance: In HFD-fed mice, GSK1940029 treatment (30 mg/kg, oral, daily) for 4 weeks significantly improved glucose tolerance, as demonstrated by a ~30% reduction in area under the curve (AUC) during an oral glucose tolerance test (OGTT) [1] |
| Enzyme Assay |
1. Recombinant SCD1 enzyme activity assay: Recombinant human or mouse SCD1 protein was purified and resuspended in assay buffer containing NADPH, cytochrome b5, and ATP (cofactors for SCD activity). Serial concentrations of GSK1940029 (0.001–1 μM) were pre-incubated with the enzyme mixture for 20 minutes at 37°C. [1-¹⁴C]-stearoyl-CoA (substrate) was added to initiate the reaction, which was incubated at 37°C for 60 minutes. The reaction was terminated by adding hydrochloric acid-methanol, and fatty acids were extracted with hexane. The radioactive product (oleoyl-CoA) was separated by thin-layer chromatography (TLC) and quantified using a scintillation counter. The IC50 value was calculated by plotting the percentage of enzyme activity (relative to vehicle control) against the log concentration of GSK1940029 [1]
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| Cell Assay |
1. Cellular SCD activity assay: HepG2 or 3T3-L1 cells were seeded in 6-well plates at a density of 2×10⁵ cells/well and cultured overnight. The cells were pre-treated with GSK1940029 (0.01–1 μM) for 2 hours, then incubated with [1-¹⁴C]-stearic acid for 24 hours. Lipids were extracted from cells using chloroform-methanol, and fatty acids were methylated. The methyl esters were analyzed by gas chromatography (GC) with a radioactivity detector to quantify the conversion of stearic acid (C18:0) to oleic acid (C18:1n9) [1]
2. Cancer cell proliferation assay: MCF-7 or A549 cells were seeded in 96-well plates at 5×10³ cells/well and cultured overnight. GSK1940029 was added at gradient concentrations (0.001–1 μM), and the cells were incubated for 72 hours. Cell viability was measured using a colorimetric assay, and the EC50 for proliferation inhibition was calculated. For cell cycle analysis, cells were harvested, fixed with ethanol, stained with propidium iodide (PI), and analyzed by flow cytometry [1] |
| Animal Protocol |
1. Hepatic SCD inhibition mouse model: Male C57BL/6 mice (6–8 weeks old) were randomly divided into 4 groups (n=6 per group): vehicle control, 10 mg/kg, 30 mg/kg, or 100 mg/kg GSK1940029. The drug was formulated in 0.5% methylcellulose and administered orally via gavage once daily for 7 days. On day 8, mice were euthanized, and livers were excised. Hepatic SCD1 enzyme activity was measured using the recombinant enzyme assay protocol, and fatty acid composition was analyzed by GC [1]
2. Diet-induced obesity mouse model: Male C57BL/6 mice were fed a high-fat diet (60% kcal from fat) for 4 weeks to induce obesity, then randomly divided into vehicle control and GSK1940029 treatment groups (n=8 per group). The drug was administered orally at 30 mg/kg once daily for an additional 4 weeks, with continuous HFD feeding. Body weight was measured weekly, and food intake was recorded daily. At the end of treatment, mice were subjected to an OGTT, then euthanized. Epididymal fat pads and livers were weighed, and hepatic triglyceride levels were quantified using a colorimetric assay [1] |
| ADME/Pharmacokinetics |
1. Absorption: After oral administration of GSK1940029 (30 mg/kg) to mice, the peak plasma concentration (Cmax) reached ~1.2 μM 1.5 hours after administration. Based on a comparison of intravenous and oral pharmacokinetic data, the oral bioavailability is estimated to be approximately 42% [1] 2. Distribution: The drug is widely distributed in tissues with high SCD expression, including the liver, adipose tissue and lungs. The liver to plasma concentration ratio was approximately 15:1 4 hours after administration [1] 3. Metabolism: GSK1940029 is mainly metabolized by hepatic cytochrome P450-mediated oxidative metabolism. Two major inactive metabolites were detected in plasma [1] 4. Excretion: In mice, the plasma elimination half-life (t1/2) was approximately 6.8 hours. Approximately 65% of the administered dose is excreted in feces within 72 hours (40% as unchanged drug and 25% as metabolites), and 20% is excreted in urine (mainly as metabolites) [1]
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| Toxicity/Toxicokinetics |
1. Acute toxicity: No significant changes in death, body weight, clinical symptoms, or organ weight were observed in mice after a single oral dose of up to 500 mg/kg of GSK1940029 [1]. 2. Subchronic toxicity: No obvious hematological, biochemical, or histopathological abnormalities were observed in rats after four consecutive weeks of oral administration of GSK1940029 (10–100 mg/kg/day). A slight decrease in serum triglyceride levels was observed, which is consistent with the mechanism of action of the drug [1]. 3. Plasma protein binding: The in vitro plasma protein binding rate in mouse and human plasma was approximately 91% (measured by equilibrium dialysis), and no concentration-dependent binding was observed in the concentration range of 0.1–10 μM [1].
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| References | |
| Additional Infomation |
1. Drug Classification and Structure: GSK1940029 is a synthetic 1,2,3-triazole derivative and a selective reversible inhibitor of stearoyl-CoA desaturase (SCD)[1]. 2. Mechanism of Action: SCD is a key enzyme in fatty acid metabolism, catalyzing the desaturation of saturated fatty acids (e.g., stearic acid) into monounsaturated fatty acids (e.g., oleic acid). Inhibition of SCD activity by GSK1940029 leads to the depletion of monounsaturated fatty acids (MUFAs), which are essential for lipid synthesis, cell proliferation, and cell membrane fluidity. This mechanism is the basis for its effects on obesity, glucose metabolism, and cancer cell growth[1]. 3. Therapeutic Potential: GSK1940029 is being developed for the treatment of metabolic disorders (e.g., obesity, type 2 diabetes) and SCD-dependent cancers (e.g., breast cancer, lung cancer). Its efficacy in reducing weight, improving glucose tolerance, and inhibiting cancer cell proliferation supports its further clinical development [1]
4. Selectivity: The compound exhibits high selectivity for SCD1 and SCD5, superior to other fatty acid desaturases and enzymes involved in lipid metabolism, thereby minimizing off-target effects [1] |
| Molecular Formula |
C18H16CL2N4O2
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| Molecular Weight |
391.25124168396
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| Exact Mass |
390.065
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| Elemental Analysis |
C, 55.26; H, 4.12; Cl, 18.12; N, 14.32; O, 8.18
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| CAS # |
1150701-66-8
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| PubChem CID |
42603008
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.665
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| LogP |
2.13
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
476
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC(C=CC(CN1N=NC(C(NC2=CC=C(CO)C=C2)=O)=C1C)=C3)=C3Cl
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| InChi Key |
QQRGSFYTPBYCFD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16Cl2N4O2/c1-11-17(18(26)21-14-5-2-12(10-25)3-6-14)22-23-24(11)9-13-4-7-15(19)16(20)8-13/h2-8,25H,9-10H2,1H3,(H,21,26)
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| Chemical Name |
1-[(3,4-dichlorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyltriazole-4-carboxamide
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| Synonyms |
GSK1940029; GSK-1940029; GSK 1940029; SCD Inhibitor 1
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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 : ≥ 32 mg/mL (~81.79 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 | 2.5559 mL | 12.7796 mL | 25.5591 mL | |
| 5 mM | 0.5112 mL | 2.5559 mL | 5.1118 mL | |
| 10 mM | 0.2556 mL | 1.2780 mL | 2.5559 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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