| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
MK-4074 targets acetyl-CoA carboxylase (ACC) 1 and 2, enzymes that catalyze the carboxylation of acetyl-CoA to malonyl-CoA, the first committed step in fatty acid synthesis. ACC1 is primarily expressed in lipogenic tissues such as liver and adipose tissue, while ACC2 is expressed in oxidative tissues such as muscle and heart. By inhibiting both ACC1 and ACC2, MK-4074 reduces the production of malonyl-CoA, thereby decreasing fatty acid synthesis and increasing fatty acid oxidation. The compound has IC50 values of approximately 3 nM for both ACC1 and ACC2.
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| ln Vitro |
MK-4074 has an IC50 value of about 3 nM and substantially inhibits ACC1 and ACC2. Because MK-4074 is a substrate of the organic transporter protein (OATP) transporter, which is exclusive to hepatocytes, it is heavily attached to Manhattan. However, the MRP2 efflux transporter is necessary for the excretion of MK-4074 from hepatocytes into bile [1].
In vitro, MK-4074 demonstrates potent inhibition of both ACC1 and ACC2 with IC50 values of approximately 3 nM. The compound's liver-specific targeting suggests that it preferentially accumulates in the liver, reducing systemic exposure and potential off-target effects. As an ACC inhibitor, MK-4074 reduces fatty acid synthesis in hepatocytes. Specific cellular assay data are not detailed in the available sources beyond its characterization as a potent and liver-specific ACC inhibitor. |
| ln Vivo |
MK-4074 was administered as a single dosage in KKAy mice, a mouse model of transplantation, 2-diabetes, and fatty liver disease. The dose-dependent reduction of DNL was seen with an ID50 of one hour post-dose, and a value of 0.9 mg/kg. 30 mg/kg of MK-4074 decreased epidermal DNL by 83%, 70%, and 51% at 4, 8, and 12 hours after the experiment, respectively, in a prior time course investigation. For a maximum of eight hours, single doses of MK-4074 at 30 and 100 mg/kg markedly raised antibiotic total ketones, a surrogate biomarker for FAO, by 1.5 to 3 times [1].
Specific in vivo activity data for MK-4074 are not detailed in the available sources. As a liver-specific ACC inhibitor, the compound is expected to reduce hepatic fatty acid synthesis and improve metabolic parameters such as hepatic steatosis and dyslipidemia in vivo. The compound's liver-specific targeting suggests it may have a favorable safety profile by minimizing systemic exposure. However, specific animal model studies have not been described in the available literature. |
| Enzyme Assay |
The ACC inhibition assay for MK-4074 typically involves incubating the compound with recombinant human ACC1 or ACC2 enzyme in the presence of ATP, acetyl-CoA, and bicarbonate. The reaction is carried out in an ACC assay buffer at 37°C for a specified time. The production of malonyl-CoA is measured using a coupled enzyme assay or by HPLC. IC50 values are calculated from dose-response curves. The liver specificity can be assessed by measuring compound accumulation in liver versus other tissues.
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| Cell Assay |
To evaluate the cellular activity of MK-4074, primary human hepatocytes or hepatoma cell lines (such as HepG2 or Huh7 cells) are cultured and treated with varying concentrations of MK-4074. Fatty acid synthesis is measured by incorporating [¹⁴C]-acetate or [³H]-acetate into lipids. Alternatively, the levels of malonyl-CoA and fatty acids can be measured using LC-MS/MS. The compound's effect on ACC activity can be assessed by measuring the phosphorylation status of ACC using Western blot analysis. Cell viability is monitored to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
Specific in vivo animal experiment protocols for MK-4074 are not detailed in the available sources. As a liver-specific ACC inhibitor, the compound would typically be evaluated in animal models of non-alcoholic fatty liver disease (NAFLD) or dyslipidemia. Rodents would be fed a high-fat diet to induce hepatic steatosis and then treated with MK-4074 orally at various doses. Hepatic triglyceride content, serum lipid levels, and fatty acid oxidation rates would be measured. However, specific protocols are not described in the available literature.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for MK-4074 are not provided in the available sources. The compound is a small molecule with a molecular weight of 565.62 and a molecular formula of C33H31N3O6. Its liver-specific targeting suggests that it preferentially distributes to the liver, with limited systemic exposure. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma and liver concentrations over time using LC-MS/MS to determine key PK parameters.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK-4074 are not provided in the available sources. The compound's liver-specific targeting is designed to minimize systemic exposure and potential off-target toxicities. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment.
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| References | |
| Additional Infomation |
MK-4074 is a liver-specific inhibitor of acetyl-CoA carboxylase (ACC) ACC1 and ACC2 with IC50 values of approximately 3 nM. It is a potent and selective inhibitor that blocks ACC activity to reduce fatty acid synthesis. ACC is a key enzyme regulating fatty acid synthesis and oxidation. The compound has a molecular formula of C33H31N3O6 and a molecular weight of 565.62. It is supplied for research purposes.
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| Molecular Formula |
C33H31N3O6
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| Molecular Weight |
565.615748643875
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| Exact Mass |
565.221
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| CAS # |
1039758-22-9
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| Related CAS # |
1039758-22-9 (free acid);1039758-18-3 (sodium);
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| PubChem CID |
24964679
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
42
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=NC=C(C2C=C3C(=CC=2)OC2(CCN(C(C4=CC5=C(C(OC)=C4)C(C)=CN5C4CC4)=O)CC2)CC3=O)C=C1C(O)=O
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| InChi Key |
WDBNGXLHMZSUEI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H31N3O6/c1-19-18-36(24-4-5-24)26-13-21(14-29(41-2)30(19)26)31(38)35-9-7-33(8-10-35)15-27(37)25-12-20(3-6-28(25)42-33)22-11-23(32(39)40)17-34-16-22/h3,6,11-14,16-18,24H,4-5,7-10,15H2,1-2H3,(H,39,40)
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| Chemical Name |
5-[1'-(1-cyclopropyl-4-methoxy-3-methylindole-6-carbonyl)-4-oxospiro[3H-chromene-2,4'-piperidine]-6-yl]pyridine-3-carboxylic acid
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| Synonyms |
MK4074; MK 4074; MK-4074
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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 : ~50 mg/mL (~88.40 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.42 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 25.0 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: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7680 mL | 8.8399 mL | 17.6797 mL | |
| 5 mM | 0.3536 mL | 1.7680 mL | 3.5359 mL | |
| 10 mM | 0.1768 mL | 0.8840 mL | 1.7680 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.
Link: https://clinicaltrials.gov/ct2/show/NCT01431521
Conditions:Non-alcoholic Fatty Liver Disease
Liver Targeting ACC1 and ACC2 Inhibitor MK-4074.Cell Metab.2017 Aug 1;26(2):394-406.e6. |
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Phase 1 Clinical Pharmacology.Cell Metab.2017 Aug 1;26(2):394-406.e6. |
MK-4074 Decreased Hepatic TGs but Increased Plasma TGs in Humans.
SREBP-1c Levels are Increased in ACC dLKO Mouse Livers.Cell Metab.2017 Aug 1;26(2):394-406.e6. |
Liver TGs are Reduced in ACC dLKO Mice, but Plasma TGs are Elevated in ACC dLKO Mice.Cell Metab.2017 Aug 1;26(2):394-406.e6. |
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Dietary PUFA Supplementation Normalizes SREBP-1c in ACC dLKO Mouse Livers. |
 Liver TG Secretion from Livers of ACC dLKO Mice is Increased and Knockdown of GPAT1 Expression Normalizes Plasma TGs.Cell Metab.2017 Aug 1;26(2):394-406.e6. |
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