| Bioactivity | MK-4074 is a liver-specific inhibitor of acetyl-CoA carboxylase ACC1 and ACC2 with IC50 values of approximately 3 nM. | ||||||||||||
| Target | IC50: 3 nM (Acetyl-CoA Carboxylase) | ||||||||||||
| Invitro | MK-4074 strongly inhibits both ACC1 and ACC2 with IC50 values of approximately 3 nM. MK-4074 is highly liver specific because it is a substrate of organic anion transport protein (OATP) transporters that are present only in hepatocytes, and excretion of MK-4074 from hepatocytes into bile is dependent on the MRP2 efflux transporter[1]. | ||||||||||||
| In Vivo | In male KKAy mice, a mouse model of obesity, type 2 diabetes, and fatty liver, a single oral dose of MK-4074 (0.3-3 mg/kg) significantly decreases DNL in a dose-dependent manner with an ID50 value of 0.9 mg/kg 1 hr post-administration. In a time course study, MK-4074 orally at 30 mg/kg reduces hepatic DNL by 83%, 70%, and 51% at 4, 8, and 12 hr post-dose, respectively. Single oral doses of MK-4074 at 30 and 100 mg/kg significantly increases plasma total ketones, a surrogate biomarker for hepatic FAO, by 1.5-fold to 3-fold for up to 8 hr[1]. | ||||||||||||
| Name | MK-4074 | ||||||||||||
| CAS | 1039758-22-9 | ||||||||||||
| Formula | C33H31N3O6 | ||||||||||||
| Molar Mass | 565.62 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [1]. Kim CW, et al. Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation. Cell Metab. 2017 Aug 1;26(2):394-406.e6. |