PPAR-δ: HPP593
(MAVODELPAR)
// PPAR-δ: HPP593 (MAVODELPAR)
Overview
HPP593 (mavodelpar) is a selective and potent peroxisome proliferator-activated receptor delta (PPAR-δ) agonist that has been shown to reduce low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) in animal models and in humans, while significantly increasing high-density lipoprotein cholesterol (HDL-C).
// PPAR-δ: HPP593 (MAVODELPAR)
Clinical and Nonclinical Studies
Results from Phase 1 clinical studies in dyslipidemic participants showed that HPP593 improved HDL-C/LDL-C ratios. In addition, in a randomized, placebo-controlled Phase 1b study conducted over approximately four weeks in healthy volunteers (n=24), HPP593 prevented loss of muscle strength associated with limb immobilization.
In nonclinical animal models, HPP593 favorably modulated lipid parameters, including reductions in LDL-C and TGs and increases in HDL-C, consistent with enhanced fatty acid oxidation. Additional nonclinical data indicate effects on skeletal muscle metabolism and mitochondrial function, providing mechanistic support for observed clinical findings related to lipid metabolism and muscle strength preservation.
Mechanism of Action
PPARs are nuclear transcription factors that function as lipid sensors and play a central role in regulating lipid storage and catabolism. PPAR-δ has also been shown to regulate skeletal muscle lipid oxidation and muscle fiber-type determination and has been associated with increased muscle endurance in both mice and humans.
Mechanistic studies support HPP593’s selective activation of PPAR-δ. Computational modeling showed that HPP593 selectively fits within the ligand-binding pocket of PPAR-δ.