KVX-876

KVX-876 (also known as EJR-876-35) is a preclinical-stage small molecule chemodegrader and inhibitor of the protein tyrosine phosphatase 4A (PTP4A) family, specifically targeting PTP4A3 (PRL-3). Developed by KeViRx in collaboration with the University of Pittsburgh and the University of Virginia, KVX-876 is a bifunctional analog of the lead compound KVX-053. It consists of a PTP4A3-binding pharmacophore conjugated to an adamantyl moiety, which acts as a hydrophobic tag to induce endoplasmic reticulum (ER) stress, activate the unfolded protein response (UPR), and promote proteasomal degradation of the target protein. KVX-876 has demonstrated potent in vitro cytotoxicity against various cancer models, including ovarian cancer, triple-negative breast cancer, and leukemia.