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

  • J Med Chem. 2021 Jun 10;64(11):7261-7271. doi: 10.1021/acs.jmedchem.1c00599.
Bryan Oronsky  1 ,  XiaoNing Guo  2 ,  XiaoHui Wang  2 ,  Pedro Cabrales  3 ,  David Sher  4 ,  Lou Cannizzo  5 ,  Bob Wardle  5 ,  Nacer Abrouk  1 ,  Michelle Lybeck  1 ,  Scott Caroen  1 ,  Arnold Oronsky  6 ,  Tony R Reid  1
Affiliations
  • 1. EpicentRx Inc., 11099 North Torrey Pines Road, Suite 160, La Jolla, California 92037, United States.
  • 2. SciClone Pharmaceuticals Co., Ltd., 22 Floor, Shanghai Central Plaza, No. 381 Middle Huaihai Road, Huangpu, Shanghai 200020, China.
  • 3. Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
  • 4. Department of Radiation Oncology, UT Southwestern Medical Center, 2280 Inwood Road, Dallas, Texas 75390, United States.
  • 5. Department of Space Systems, Northrop Grumman Corporation, 2980 Fairview Park Drive, Falls Church, Virginia 22042, United States.
  • 6. InterWest Partners, 467 First Street, Suite 201, Los Altos, California 94022, United States.
PMID: 34043360 DOI: 10.1021/acs.jmedchem.1c00599
Abstract

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.