20-hydroxyvitamin D3

20-hydroxyvitamin D3 (20(OH)D3) is a naturally occurring, non-calcemic metabolite of vitamin D3 produced by the enzymatic action of CYP11A1 (cytochrome P450scc). Unlike the primary active form of vitamin D, 1,25-dihydroxyvitamin D3, 20-hydroxyvitamin D3 does not induce hypercalcemia at therapeutic doses, making it a safer candidate for high-dose therapy. It functions primarily as a partial agonist of the vitamin D receptor (VDR) and also acts as an agonist for the liver X receptors (LXR) and aryl hydrocarbon receptor (AhR), while serving as an inverse agonist for retinoic acid-related orphan receptors (RORα and RORγ). Preclinical research indicates that 20-hydroxyvitamin D3 possesses potent antiproliferative, anti-inflammatory, and pro-differentiation properties, showing efficacy in models of melanoma and rheumatoid arthritis. It is often studied for its ability to synergize with other anticancer agents, such as BRAF inhibitors, by suppressing oncogenic signaling pathways like AKT, ERK, and NF-κB.

Other names

20-hydroxycholecalciferol