ORIC-101

ORIC-101 is a potent and selective small molecule antagonist of the glucocorticoid receptor (GR), developed by ORIC Pharmaceuticals. It is an orally bioavailable, mifepristone-based steroidal compound designed to inhibit GR-mediated signaling pathways that drive resistance to multiple classes of cancer therapeutics, including taxanes and androgen receptor modulators, across a variety of solid tumors. By selectively binding to the glucocorticoid receptor, ORIC-101 blocks activation of proliferative and anti-apoptotic gene expression programs mediated by GR signaling. Preclinical studies demonstrated that ORIC-101 can reverse chemoprotection induced by glucocorticoids and restore sensitivity to chemotherapy in resistant tumor models. Clinical trials have evaluated its use in combination with nab-paclitaxel for advanced solid tumors and with enzalutamide for metastatic castration-resistant prostate cancer; however, both studies were terminated after failing to meet prespecified efficacy endpoints[1][2][3][4][5][6][8].