New Molecules to Tackle Autoimmune Diseases Linked to BAFF

The B-cell activating factor (BAFF) is a cytokine, a type of protein that helps immune cells communicate with each other. Its main role is to stimulate the growth and maturation of B cells, the cells responsible for producing antibodies.

Previous studies have shown that when BAFF is overproduced—due to genetic factors—it leads to an excess of circulating B cells and antibodies. This imbalance has been linked to a higher risk of developing multiple sclerosis and systemic lupus erythematosus, two serious autoimmune diseases. These findings suggest that BAFF plays a direct role in triggering such conditions, making it an attractive target for new therapies.

So far, however, no small-molecule drugs capable of blocking BAFF have been developed. To address this, researchers used an innovative approach: they virtually screened a massive library of 275,561 molecules, then tested 218 of the most promising candidates in the lab to see if they could prevent BAFF from binding to its receptor, BAFFR.

The search paid off. Two molecules, named C45 and C145—part of the substituted 2-pyrrolinone family—showed strong potential to inhibit BAFF activity.

Although still at an early stage, these results pave the way for further studies. If confirmed, C45 and C145 could represent a new therapeutic strategy for autoimmune diseases driven by BAFF, offering fresh hope for patients with conditions such as lupus and multiple sclerosis.