JD128

JD128 is a novel, orally bioavailable selective estrogen receptor degrader (SERD) designed to target both wild-type and mutant forms of estrogen receptor alpha (ERα), including common resistance-associated mutations such as Y537S and D538G. Developed by researchers at UCLA, JD128 functions by inducing the degradation of ERα protein and reducing ESR1 mRNA levels, thereby inhibiting ligand-independent ER signaling. Beyond its direct anti-proliferative effects on breast cancer cells, JD128 has been shown to modulate the tumor microenvironment by inhibiting the expansion of immunosuppressive myeloid-derived suppressor cells (MDSCs) and increasing T-cell infiltration. It is being investigated for the treatment of hormone-resistant, ER-positive breast cancer.