VDR agonist 4 is a potent VDR agonist that is effective when administered orally. It exhibits VDR-dependent antifibrotic activity by modulating various fibrosis-related genes, thereby inhibiting the production of α-SMA and collagen I and suppressing the activation of hepatic stellate cells. VDR agonist 4 can ameliorate liver fibrosis in mice induced by CCl4 and is useful for research related to liver fibrosis.

VDR agonist 4, also known as compound B15, at a concentration of 0.1 μM over 48 hours, reduces the expression of 991 differentially expressed genes (DEGs) and increases the expression of 249 DEGs in LX-2 cells while enhancing CYP24A1 expression. It exhibits high safety with no significant cytotoxicity to LX-2 cells (IC50 > 50 μM) and negligible hERG-mediated cardiotoxicity (IC50 > 30 μM). At 0.1 μM for 24 hours, VDR agonist 4 significantly inhibits the expression of COL1A1, ACTA2, and type I collagen in LX-2 cells; this antifibrotic effect disappears upon VDR depletion, indicating its reliance on VDR for its potent antifibrotic activity. The compound also downregulates key profibrotic pathways (TGFβ/SMAD3, PEGF, JAK) and collagen synthesis genes (COL1A2, COL3A1) while upregulating collagen degradation genes (MMP1, MMP3) in LX-2 cells over 48 hours at 0.1 μM, confirming its ability to inhibit collagen production and promote collagen degradation.

VDR agonist 4 (500 μg/kg, oral, 5 times per week, for 2 weeks) effectively alleviates the inflammatory response and fibrotic remodeling in CCI 4-induced liver fibrosis in mice.