KB3495

KB3495 is a synthetic small molecule thyroid hormone mimetic developed as a selective thyroid hormone receptor beta (THRβ) modulator. It is primarily investigated for its potential to treat dyslipidemia and atherosclerosis by reducing serum cholesterol and atherosclerotic plaque formation, primarily through enhanced sterol excretion and inhibition of inflammatory responses, without the adverse cardiac effects typical of non-selective thyroid hormone analogues. KB3495 is a racemate composed of two enantiomers; subsequent development shifted focus to one enantiomer, KB5359, for advanced preclinical investigations. Studies in animal models have shown significant reductions in hepatic cholesterol synthesis, cholesteryl ester levels, macrophage infiltration in plaques, and circulating inflammatory cytokines, with a distinct mechanism from statins that does not primarily lower total cholesterol but instead acts through receptor-modulated metabolic pathways[1][3][4][7].