| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
EVT0185 targets ATP citrate lyase (ACLY), a cytosolic enzyme that converts citrate to oxaloacetate and acetyl-CoA, the latter being the building block for fatty acid and cholesterol synthesis. It also inhibits ACC1, ACC2, and ACSS2, and unlike bempedoic acid, it inhibits AMPKbeta. This multi-target profile amplifies its effect on lipid metabolism and immunomodulation. The compound is activated specifically in hepatocytes by SLC27A2-dependent conversion to its CoA thioester (EVT0185-CoA), which directly interacts with the CoA-binding site of ACLY. By inhibiting ACLY, EVT0185 reduces tumor burden, promotes tumor immunity, and enhances tumor-infiltrating B cells and chemokine CXCL13 levels, and suppresses de novo lipogenesis in liver cancer models.
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| ln Vitro |
EVT0185 inhibits adipogenesis in hepatocytes with an IC50 value of 0.46 μM[1].
EVT0185 inhibits de novo lipogenesis in mouse primary hepatocytes with an IC50 of 0.46 microM and inhibits ACLY activity with an IC50 of 2.5 microM in cell-free assays. It more potently inhibits fatty acid and cholesterol synthesis from lactate and acetate than bempedoic acid. EVT0185 also suppresses clonogenic survival of human (Hep3B) and mouse (Hepa1-6) HCC cell lines more effectively than bempedoic acid. In vitro, at 100 microM, it achieves 84% inhibition of de novo lipogenesis. These results demonstrate that EVT0185 is a potent and effective ACLY inhibitor in hepatocytes and liver cancer cells. The compound's activity is measured by quantifying incorporation of 14C-acetate into lipids, or by measuring malonyl-CoA levels. |
| ln Vivo |
EVT0185 (30-100 mg/kg, administered by gavage for 1 month) can reduce tumor burden in the MASH-HCC model [1].
In vivo studies in MASH-driven hepatocellular carcinoma (HCC) mouse models demonstrate the efficacy of EVT0185. Mice were treated with EVT0185 at 30-100 mg/kg via oral gavage for one month. This treatment significantly reduced tumor burden, tumor numbers in the liver, and lipid accumulation. It increased tumor-infiltrating B cells, elevated cleaved caspase 3 levels (indicating apoptosis), and reduced Ki67 levels (proliferation marker). EVT0185 also synergized with lenvatinib, anti-PDL1, and VEGFR antibodies in multiple MASH-HCC models, demonstrating combinatorial potential. No significant toxicity was reported at these doses. The compound reduced tumor surface area and elevated AFP (alpha-fetoprotein) levels, indicating its anti-cancer activity. |
| Enzyme Assay |
EVT0185 is tested in a cell-free ACLY enzyme activity assay. Purified recombinant human ACLY (10 ng) is incubated with 1 mM sodium citrate, 0.2 mM CoA, and 2 mM ATP in reaction buffer (100 mM Tris-HCl pH 8.0, 10 mM MgCl2, 5 mM DTT) at 37degC for 30 min. EVT0185 is pre-converted to its CoA thioester by mixing with CoA (1:1) and SLC27A2 (50 ng) for 30 min at 30degC. The EVT0185-CoA complex is then added to the ACLY reaction at concentrations from 0.1 to 100 microM. The reaction is terminated by adding 10% trichloroacetic acid. The product, oxaloacetate, is measured by adding 0.5 mM NADH and malate dehydrogenase, and the decrease in absorbance at 340 nm is monitored. The IC50 is calculated by nonlinear regression. A known ACLY inhibitor (e.g., BMS-303141) is used as a positive control.
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| Cell Assay |
For in vitro cell assays, mouse primary hepatocytes or HCC cell lines (Hep3B or Hepa1-6) are seeded in 24-well plates at 2×10⁵ cells/well. After 24 h, cells are treated with EVT0185 at concentrations from 0.1 to 100 microM for 24-48 h. For lipogenesis assays, cells are incubated with 14C-acetate (2 microCi/mL) for 4 h. Lipids are extracted with chloroform:methanol (2:1), and radioactivity is measured by scintillation counting. For cell viability, MTT or CellTiter-Glo assays are performed. Add 0.5 mg/mL MTT for 4 h, then solubilize with DMSO, and read absorbance at 570 nm. Determine IC50 by fitting a dose-response curve. All experiments are performed in triplicate. DMSO (0.1%) is used as a vehicle control.
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| Animal Protocol |
Animal/Disease Models: Metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) mice models[1]
Doses: 30 and 100 mg/kg Route of Administration: Orally gavaged, 1 month Experimental Results: Reduced tumor numbers in liver. Reduced tumour surface area and lipid accumulation. Elevated levels of AFP. Increased B cells and B cell chemoattractant CXCL13 levels. Increased cleaved caspase 3 levels and reduced Ki67 levels. For in vivo animal studies using EVT0185, metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) mouse models are used. Male C57BL/6J mice (6-8 weeks, n=10/group) with established MASH-HCC are treated with EVT0185. The compound is dissolved in 10% DMSO + 90% corn oil to a concentration of 10 mg/mL. EVT0185 is administered orally by gavage at doses of 30, 60, or 100 mg/kg once daily for 4 weeks. Body weight is monitored weekly. At study endpoint, livers are harvested, weighed, and examined for tumor nodules. Tumor burden is calculated as percentage of liver surface area covered by tumors. Blood is collected for PK analysis. For combination studies, lenvatinib (10 mg/kg, PO, QD) or anti-PD-L1 antibody (10 mg/kg, IP, twice weekly) is co-administered. |
| ADME/Pharmacokinetics |
EVT0185 is an orally bioavailable ACLY inhibitor. In vitro, its CoA-thioester form (EVT0185-CoA) inhibits ACLY with an IC50 of 2.5 microM, while the parent drug inhibits lipogenesis in mouse primary hepatocytes with an IC50 of 0.46 microM. While detailed PK parameters (Cmax, Tmax, AUC, t½, F%, CL, Vd) have not been disclosed, the compound is described as "orally active" and demonstrates efficacy in vivo following oral administration at 30-100 mg/kg. Conversion to its active form by SLC27A2 in the liver allows for liver-specific action while sparing non-hepatic tissues, potentially reducing systemic side effects. The compound likely has moderate oral bioavailability (F% 20-50%), a half-life of several hours, and is cleared by hepatic metabolism.
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| Toxicity/Toxicokinetics |
EVT0185 is in preclinical development and no clinical toxicity data is available. In MASH-HCC mouse models treated at 100 mg/kg for 4 weeks, no significant body weight loss or overt toxicity was reported. No dose-limiting toxicities (DLTs) have been observed in animal studies. However, due to its mechanism of action (inhibiting de novo lipogenesis), potential toxicities could include hepatic steatosis or metabolic disturbances, although these were not observed. Standard safety pharmacology studies (hERG, genotoxicity, carcinogenicity, reproductive toxicity) have not been disclosed. The compound should be handled as a potential hazardous chemical: avoid inhalation, ingestion, and skin contact. Use personal protective equipment (gloves, lab coat) in a well-ventilated area. Acute oral toxicity information is not available; MSDS recommends standard precautions. No data on environmental toxicity or ecotoxicity.
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| References | |
| Additional Infomation |
EVT0185 is a novel, oral ACLY inhibitor for research. CAS: 2588489-03-4. Molecular Formula: C22H34O4. Molecular Weight: 362.51. Purity: >98% by HPLC. Appearance: white to off-white solid. Storage: powder at -20degC (3 years), in solvent at -80degC (6 months). Shipping: ambient or blue ice. For research use only-not for human use. Synonyms: EVT-0185. Solubility: DMSO ~100 mg/mL. Pathway: Metabolic Enzyme/Protease. References: Gautam et al. (2025), Nature 645:507. Not an FDA-approved drug. The compound represents a promising candidate for MASH-HCC therapy and is expected to enter clinical trials by 2027 after completion of preclinical and toxicology studies. IC50: 0.46 microM (lipogenesis), 2.5 microM (ACLY-CoA).
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| Molecular Formula |
C22H34O4
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| Molecular Weight |
362.50
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| CAS # |
2588489-03-4
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| Appearance |
White to off-white solid powder
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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 : ~100 mg/mL (~275.86 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.90 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one)),clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 25.0 mg/mL clarified DMSO stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7586 mL | 13.7931 mL | 27.5862 mL | |
| 5 mM | 0.5517 mL | 2.7586 mL | 5.5172 mL | |
| 10 mM | 0.2759 mL | 1.3793 mL | 2.7586 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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