RRx-001 and the "Right stuff": Protection and treatment in outer space

Life Sci Space Res (Amst). 2022 Nov:35:69-75. doi: 10.1016/j.lssr.2022.05.001. Epub 2022 May 12.

Abstract

From antibiotics to aspirin to antimalarials and to anticancer agents, about half of the world's best-selling drugs are derived from nature. However, accelerating climatic disruption, habitat destruction, pollution, and biodiversity loss all negatively impact the potential of natural sources to continue to serve as repositories of novel pharmaceuticals. On that basis, the final frontier for drug development is perhaps not the rainforests, coral reefs, and other natural habitats but rather the aerospace industry with its virtually unlimited and inexhaustible man-made 'library' of potentially bioactive compounds. The first aerospace-sourced therapeutic to reach the clinic is RRx-001, an inhibitor of the NOD-like receptor - Nucleotide-binding oligomerization domain with Leucine rich Repeat and Pyrin domain (NLRP3) inflammasome in a Phase 3 trial for the treatment of small cell lung cancer (SCLC) and in a soon-to-start Phase 3 trial for protection against chemoradiotherapy-induced severe oral mucositis in first line head and neck cancer. As manned missions to the Moon, Mars, and asteroids as well as space tourism beckon, it is perhaps fitting that a compound like RRx-001, which is derived from 1,3,3-Trinitroazetidine (TNAZ), an explosive propellant for rockets, is a potential "all purpose" option to mitigate the major biomedical effects of space radiation exposures including cancer development and other tissue degenerations both within mission and after mission. This article highlights the promise of RRx-001 to attenuate the acute and late effects of radiation exposure on astronauts including the development of cancer.

Keywords: RRx-001; Radiation; Radiation countermeasures; Space.

MeSH terms

  • Astronauts
  • Azetidines* / pharmacology
  • Azetidines* / therapeutic use
  • Clinical Trials, Phase III as Topic
  • Extraterrestrial Environment
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / prevention & control
  • Space Flight*

Substances

  • Azetidines
  • RRx-001