VK2809 (MB07811)
VK2809 is a liver-targeted thyroid hormone receptor beta agonist prodrug in clinical development for MASH and dyslipidaemia. A phosphonate prodrug cleaved in hepatocytes, it concentrates its thyromimetic action in the liver, lowering liver fat and LDL with little systemic exposure.
01 Overview
VK2809 uses a HepDirect prodrug strategy: the inactive parent is activated by a liver-specific CYP enzyme, so active drug is generated mainly in hepatocytes. This targets TR-beta effects to the liver, reducing hepatic fat and cholesterol while minimising cardiac and systemic exposure. Phase 2 trials in MASH have shown meaningful liver-fat reductions.
As an investigational drug with positive mid-stage human data, it draws interest as a metabolic agent, though it is not approved and off-label physique use is unstudied.
02 Mechanism
Liver-activated prodrug releasing a thyroid hormone receptor beta agonist inside hepatocytes, upregulating hepatic lipid oxidation and LDL clearance with limited systemic thyromimetic exposure.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Phase 2 (MASH) | 5–10 mg/day | Oral | Trial dosing; not approved |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced liver fatSignificant liver-fat lowering on MRI in phase 2 MASH trials. | Large hepatic fat reduction | Clinical | |
| LDL and lipid loweringReduces LDL cholesterol and atherogenic lipids. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal upsetNausea and loose stools reported in trials. | Mild | Common | Clinical | |
| Transaminase changesLiver enzyme fluctuations possible given hepatic targeting. | Moderate | Uncommon | Clinical |