Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development

 Bryan Oronsky, XiaoNing Guo, XiaoHui Wang, Pedro Cabrales, David Sher, Lou Cannizzo, Bob Wardle, Nacer Abrouk, Michelle Lybeck, Scott Caroen, Arnold Oronsky, and Tony R. Reid

Journal of Medicinal Chemistry 2021

DOI: 10.1021/acs.jmedchem.1c00599

After extensive screening of aerospace compounds in an effort to source a novel anticancer agent, RRx-001, a first-in-class dinitroazetidine small molecule, was selected for advancement into preclinical and clinical development. RRx-001 is a minimally toxic small molecule with a distinct chemical structure and mechanism of action. The paradox of RRx-001 is that it mediates both antitumor cytotoxicity and normal tissue protection. The question of exactly how RRx-001 does this, and by means of what mechanism(s), depending on the route of delivery, intravenous or intratumoral, are explored. RRx-001 is currently in phase 2 and 3 clinical trials for the treatment of multiple solid tumor malignancies and as a supportive care drug.