RRx-001

• CAT Number: I005506
• CAS Number: 925206-65-1
• Molecular Formula: C5H6BrN3O5
• Molecular Weight: 268.02
• Purity: ≥95%
• Synonyms: RRx001;RRx 001
• Target: G6PD
• Solubility: 10 mM in DMSO
• Storage: Store at -20C
• IC50: 0.14 ± 0.04 ug/ml
• InChI: InChI=1S/C5H6BrN3O5/c6-1-4(10)7-2-5(3-7,8(11)12)9(13)14/h1-3H2
• InChIKey: JODKFOVZURLVTG-UHFFFAOYSA-N
• SMILES: O=[N+](C1([N+]([O-])=O)CN(C(CBr)=O)C1)[O-]

RRx-001 is a potent inhibitor of G6PD. RRx-001 shows potent antimalarial, although as a single agent, the drug sensitivity testing indicated that higher dose of RRx-001 was required to inhibited 50 % of the parasite/’s activity (IC50 = 0.14 ± 0.04 ug/ml).

in vitro: RRx-001 is a novel, systemically non-toxic, epigenetic anticancer agent for multiple tumour types, with activity mediated through increased nitric oxide (NO) production and PPP inhibition. [1]

in vivo: RRx-001is a novel, nonexplosive molecule modified from a class of solid rocket propellants, has shown promise as a novel cancer therapeutic agent in a number of cell lines and tumor models. In mouse models, RRx-001 administered intravenously as a single agent was equipotent to cisplatin while better tolerated. RRx-001 also showed activity as a radiosensitizer in both in vitro and in vivo models. The activity of RRx-001 is thought to be associated with a nucleophilic substitution by circulating thiol compounds and covalent binding of RRx-001 to cysteinyl residues in Hb, followed by the generation of nitrogen oxides. [2]

Reference

1. Brzezniak, C., Oronsky, B., Trepel, J., Summers, T. A. Jr, Cabrales, P., Lee, M. J., Day, R., Jha, S., Caroen, S., Zeman, K., Ferry, L., Harmer, C., Oronsky, N., Lybeck, M., Lybeck, H. E., Brown, J. F., Reid, T. R., Carter, C. A. (2017). Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor. *Case Reports in Oncology, 10*(1), 276-280. doi: 10.1159/000464101. [Free PMC Article](https://pubmed.ncbi.nlm.nih.gov/28512410/)

2. Cabrales, P., Caroen, S., Oronsky, A., Carter, C., Trepel, J., Summers, T. Jr, Reid, T., Oronsky, N., Lybeck, M., Oronsky, B. (2017). The macrophage stimulating anti-cancer agent, RRx-001, protects against ischemia-reperfusion injury. *Expert Review of Hematology.* doi: 10.1080/17474086.2017.1324779. [Epub ahead of print] PMID: 28448172

3. Oronsky, B., Reid, T. R., Larson, C., Carter, C. A., Brzezniak, C. E., Oronsky, A., Cabrales, P. (2017). RRx-001 protects against cisplatin-induced toxicities. *Journal of Cancer Research and Clinical Oncology.* doi: 10.1007/s00432-017-2416-4. [Epub ahead of print] PMID: 28417195

4. Zhao, H., Ning, S., Nolley, R., Scicinski, J., Oronsky, B., Knox, S. J., Peehl, D. M. (2017). The immunomodulatory anticancer agent, RRx-001, induces an interferon response through epigenetic induction of viral mimicry. *Clinical Epigenetics, 9*, 4. doi: 10.1186/s13148-017-0312-z. [Free PMC Article](https://pubmed.ncbi.nlm.nih.gov/28149332/)

5. Oronsky, B., Paulmurugan, R., Foygel, K., Scicinski, J., Knox, S. J., Peehl, D., Zhao, H., Ning, S., Cabrales, P., Summers, T. A. Jr, Reid, T. R., Fitch, W. L., Kim, M. M., Trepel, J. B., Lee, M. J., Kesari, S., Abrouk, N. D., Day, R. M., Oronsky, A., Ray, C. M., Carter, C. A. (2017). RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials. *Expert Opinion on Investigational Drugs, 26*(1), 109-119. doi: 10.1080/13543784.2017.1268600. Review. Erratum in: *Expert Opinion on Investigational Drugs.* 2017 Feb; 26(2):261. PMID: 27935336

6. Brzezniak, C., Oronsky, B., Scicinski, J., Caroen, S., Cabrales, P., Dean Abrouk, N., Kim, M. M., Brown, J. F., Reid, T. R., Larson, C., Oronsky, A., Day, R., Degesys, A., Carter, C. A. (2016). Conversion of Platinum-Etoposide-Resistant to Sensitive SCLC after Treatment with the Epi-Immunotherapeutic RRx-001: A Case Report. *Oncology Research and Treatment, 39*(11), 720-723. [Epub 2016 Sep 19] PMID: 27855386

7. Oronsky, B., Caroen, S., Zeman, K., Quinn, M., Brzezniak, C., Scicinski, J., Cabrales, P., Reid, T. R., Trepel, J. B., Abrouk, N. D., Larson, C., Oronsky, A., Lybeck, H. E., Day, R. M., Carter, C. A. (2016). A Partial Response to Reintroduced Chemotherapy in a Resistant Small Cell Lung Cancer Patient After Priming with RRx-001. *Clinical Medicine Insights: Oncology, 10*, 105-108. [Epub 2016] PMID: 27840583 [Free PMC Article](https://pubmed.ncbi.nlm.nih.gov/27840583/)

8. Das, D. S., Ray, A., Das, A., Song, Y., Tian, Z., Oronsky, B., Richardson, P., Scicinski, J., Chauhan, D., Anderson, K. C. (2016). A novel hypoxia-selective epigenetic agent RRx-001 triggers apoptosis and overcomes drug resistance in multiple myeloma cells. *Leukemia, 30*(11), 2187-2197. doi: 10.1038/leu.2016.96. [Epub 2016 Apr 27] PMID: 27118403 [Free PMC Article](https://pubmed.ncbi.nlm.nih.gov/27118403/)

9. Carter, C. A., Oronsky, B., Caroen, S., Scicinski, J., Degesys, A., Cabrales, P., Reid, T. R., Brzezniak, C. (2016). Partial Response in an RRx-001-Primed Patient with Refractory Small-Cell Lung Cancer after a Third Introduction of Platinum Doublets. *Case Reports in Oncology, 9*(2), 285-289. doi: 10.1159/000446209. [Epub 2016 May 24] [Free PMC Article](https://pubmed.ncbi.nlm.nih.gov/27403127/)

10. Fens, M. H., Cabrales, P., Scicinski, J., Larkin, S. K., Suh, J. H., Kuypers, F. A., Oronsky, N., Lybeck, M., Oronsky, A., Oronsky, B. (2016). Targeting tumor hypoxia with the epigenetic anticancer agent, RRx-001: a superagonist of nitric oxide generation. *Medical Oncology, 33*(8), 85. doi: 10.1007/s12032-016-0798-9. [Epub 2016 Jul 4] PMID: 2737742