Discovery and Preclinical Profile of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta (THR-β) Agonist for the Treatment of MASH

Agonists of thyroid hormone receptor
β (THR-β)
decreased
LDL cholesterol (LDL-C) and triglyceride (TG) levels in human clinical
trials for patients with dyslipidemia. The authors present the highly
potent and selective compound ALG-055009 (14) as a potential
best in class THR-β agonist. The high metabolic stability and
good permeability translated well in vivo to afford a long in vivo
half-life pharmacokinetic profile with limited liability for DDI,
and it overcomes certain drawbacks seen in recent clinical candidates.