Rockets, radiosensitizers, and RRx-001: an origin story part I.
From Adam and Eve, to Darwinism, origin stories attempt to fill in the blanks, connect the dots, and define the turning points that are fundamental to subsequent developments. The purpose of this review is to present the origin story of a one-of-a-kind anticancer agent, RRx-001, which emerged from the aerospace industry as a putative radiosensitizer; not since the dynamite-to-dilator transformation of nitroglycerin in 1878 or the post-World War II explosive-to-elixir conversion of hydralazine, an ingredient in rocket fuel, to an antihypertensive, an antidepressant and an antituberculant, has energetic chemistry been harnessed for therapeutic purposes. This is Part 1 of the radiosensitization story; Parts 2 and 3, which detail the crossover activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews.
EpicentRx Inc., 800 W. El Camino Real, Suite 180, Mountain View, CA 94040, USA.
Bryan
B
Oronsky
EpicentRx Inc., 800 W. El Camino Real, Suite 180, Mountain View, CA 94040, USA.
Jan
J
Scicinski
Stanford University, 875 Blake Wilbur Dr. Clinic D, Stanford, CA 94305, USA.
Shoucheng
S
Ning
Stanford University, 875 Blake Wilbur Dr. Clinic D, Stanford, CA 94305, USA.
Donna
D
Peehl
InterWest Partners, 2710 Sand Hill Rd. #200, Menlo Park, CA 94025, USA.
Arnold
A
Oronsky
Department of Bioengineering, University of California at San Diego (UCSD), 9500 Gilman Dr., La Jolla, CA 92093, USA.
Pedro
P
Cabrales
Stanford University, 875 Blake Wilbur Dr. Clinic D, Stanford, CA 94305, USA.
Mark
M
Bednarski
Stanford University, 875 Blake Wilbur Dr. Clinic D, Stanford, CA 94305, USA.
Susan
S
Knox
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001384:Azetidines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D044127:Epigenesis, Genetic; D053834:Explosive Agents / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000532:radiotherapy*; D009574:Nitro Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001384:Azetidines; D053834:Explosive Agents; D009574:Nitro Compounds; C577469:RRx-001; D011838:Radiation-Sensitizing Agents