We designed and synthesized a series of 37 non-steroidal compounds aimed at activating the vitamin D receptor (VDR) to explore their potential in treating liver fibrosis. This condition involves an unhealthy buildup of fibrous tissue in the liver, often leading to serious complications.
Our research found that more than a third of these novel compounds displayed strong affinity for VDR and showed the ability to activate it. Among these, one compound, E15, stood out as particularly effective. It significantly inhibited the activation of hepatic stellate cells (HSCs), which play a critical role in the progression of liver fibrosis, thereby reducing the production of harmful extracellular matrix components.
Encouraged by these promising in vitro results, we proceeded to test E15 in a mouse model of liver fibrosis induced by carbon tetrachloride. The results were remarkable; E15 not only decreased fibrosis and collagen deposition, but also improved liver function without the negative side effect of hypercalcemia, which is often associated with traditional VDR agonists.
These findings suggest that E15 could be a powerful and safer alternative for addressing liver fibrosis, highlighting the significant therapeutic potential of targeting the vitamin D receptor in liver diseases.