Synonyms: ABDNAZ [2] | RRx-001 | RRx001
Compound class:
Synthetic organic
Comment: RRx-001 (EpicentRx) was originally developed as an anti-tumour agent [3]; it promotes apoptosis, and has radio- , chemo- and immuno-sensitising actions in cancer models. It also provides cytoprotective effects in normal tissues, which has led to the proposal of RRx-001 as a supportive care drug in patients undergoing cytotoxic cancer therapy. RRx-001 was identified using phenotypic screening, so its molecular mechanism of action was initially unclear. Several mechanisms have subsequently been identified, including NLRP3 inflammasome inhibition [1,4] and CD47/SIRP-α immune checkpoint inhibition. RRx-001 covalently targets the cysteine 409 residue in NLRP3's NACHT domain and blocks NLRP3/NEK7 interaction and assembly of the inflammasome complex. This ultimately inhibits release of active pro-inflammatory cytokines (IL-1β and IL-18).
RRx-001's chemical structure is a match for the INN nibrozetone (proposed INN list 130 of Feb. 2024). |
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References |
1. Jayabalan N, Oronsky B, Cabrales P, Reid T, Caroen S, Johnson AM, Birch NA, O'Sullivan JD, Gordon R. (2023)
A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation. Drugs, 83 (5): 389-402. [PMID:36920652] |
2. Ning S, Bednarski M, Oronsky B, Scicinski J, Saul G, Knox SJ. (2012)
Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials. Cancer Res, 72 (10): 2600-8. [PMID:22589277] |
3. Oronsky B, Guo X, Wang X, Cabrales P, Sher D, Cannizzo L, Wardle B, Abrouk N, Lybeck M, Caroen S et al.. (2021)
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, 64 (11): 7261-7271. [PMID:34043360] |
4. Oronsky B, Takahashi L, Gordon R, Cabrales P, Caroen S, Reid T. (2023)
RRx-001: a chimeric triple action NLRP3 inhibitor, Nrf2 inducer, and nitric oxide superagonist. Front Oncol, 13: 1204143. [PMID:37313460] |
5. Reid TR, Gordon R.
Validation of RRx-001 as a Novel Disease-modifying Therapeutic for Parkinson's Disease. Accessed on 22/02/2024. Modified on 22/02/2024. michaeljfox.org, https://www.michaeljfox.org/grant/validation-rrx-001-novel-disease-modifying-therapeutic-parkinsons-disease |