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PLoS One. 2017 Jul 21;12(7):e0181577. doi: 10.1371/journal.pone.0181577. eCollection 2017.

4-(Nitrophenylsulfonyl)piperazines mitigate radiation damage to multiple tissues.

Author information

1
Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, California, United States of America.
2
Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California, United States of America.
3
Molecular Screening Shared Resource, University of California at Los Angeles, Los Angeles, California, United States of America.
4
Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, Los Angeles, California, United States of America.
5
Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California, United States of America.
6
School of Public Health, Biostatistics and Radiology, University of California at Los Angeles, Los Angeles, California, United States of America.
7
BCN Biosciences, LLC, Pasadena, California, United States of America.

Abstract

Our ability to use ionizing radiation as an energy source, as a therapeutic agent, and, unfortunately, as a weapon, has evolved tremendously over the past 120 years, yet our tool box to handle the consequences of accidental and unwanted radiation exposure remains very limited. We have identified a novel group of small molecule compounds with a 4-nitrophenylsulfonamide (NPS) backbone in common that dramatically decrease mortality from the hematopoietic acute radiation syndrome (hARS). The group emerged from an in vitro high throughput screen (HTS) for inhibitors of radiation-induced apoptosis. The lead compound also mitigates against death after local abdominal irradiation and after local thoracic irradiation (LTI) in models of subacute radiation pneumonitis and late radiation fibrosis. Mitigation of hARS is through activation of radiation-induced CD11b+Ly6G+Ly6C+ immature myeloid cells. This is consistent with the notion that myeloerythroid-restricted progenitors protect against WBI-induced lethality and extends the possible involvement of the myeloid lineage in radiation effects. The lead compound was active if given to mice before or after WBI and had some anti-tumor action, suggesting that these compounds may find broader applications to cancer radiation therapy.

PMID:
28732024
PMCID:
PMC5521796
DOI:
10.1371/journal.pone.0181577
[Indexed for MEDLINE]
Free PMC Article

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