Related Research

Clinical

Pathmanandavel S, Crumbaker M, Yam AO, Nguyen A, Rofe C, Hovey E, Gedye C, Kwan EM, Hauser C, Azad AA, Eu P, Martin AJ, Joshua AM, Emmett L. 177Lutetium PSMA-617 and idronoxil (NOX66) in men with end-stage metastatic castrate-resistant prostate cancer (LuPIN): Patient outcomes and predictors of treatment response of a Phase I/II trial. J Nucl Med. 2021 Jul 29:jnumed.121.262552. https://doi.org/10.2967/jnumed.121.262552
Kiknavelidze K, Shavdia M, Chikhladze N, Abshilava L, Messina M, Mautner G, Kelly G. NOX66 as Monotherapy, and in Combination With Carboplatin, in Patients With Refractory Solid Tumors: Phase Ia/b Study. Curr Ther Res Clin Exp. 2021 Mar 8;94:.DOI: 10.1016/j.curtheres.2021.100631
Crumbaker M, Pathmanandavel S, Yam A, Nguyen A, Ho B, Chan L, Ende J, Rofe C, Kongrak K, Kwan E, Azad A, Sharma S, Pugh T, Danesh A, Keane J, Eu P, Joshua A, Emmett L (2020). Phase I/II Trial of the Combination of ¹⁷⁷Lutetium Prostate specific Membrane Antigen 617 and Idronoxil (NOX66) in Men with End-stage Metastatic Castration-resistant Prostate Cancer (LuPIN). European Urology Oncology. https://doi.org/10.1016/j.euo.2020.07.002
de Souza PL, Capp AL, Chikhladze N, Mezvrishvili Z, Messina M, Mautner G. Phase I study of a novel S1P inhibitor, NOX66, in combination with radiotherapy in patients with metastatic castration-resistant prostate cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 5533-5533. DOI: 10.1200/JCO.2020.38.15_suppl.5533
de Souza PL, Messina M, Minns I, Shavdia M, Chikhladze N, Kelly G. A phase 1 study of NOX66 in combination with carboplatin in patients with end stage solid tumours. DOI: 10.1200/JCO.2018.36.15_suppl.2585

Anti-Cancer

Morré, DJ, Morré, DM. Cell surface NADH oxidases (ECTO-NOX proteins) with roles in cancer, cellular time-keeping, growth, aging and neurodegenerative diseases Free Radical Research. 37 (8): 795–808 https://doi.org/10.1080/1071576031000083107
Porter, K et al. Idronoxil as an Anticancer Agent: Activity and Mechanisms. Current Cancer Drug Targets, 2020, 20, 1-14. https://pubmed.ncbi.nlm.nih.gov/31899676/
De Luca, T et al. Downstream targets of altered sphingolipid metabolism in response to inhibition of ENOX2 by phenoxodiol. Biofactors, 2008, 34(3), 253-260. http://dx.doi.org/10.1002/biof.5520340310 PMID: 19734127 10.3233/BIO-2009-1079
De Luca, T et al. NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine-1-phosphate levels accompanying G1 arrest and apoptosis. Biofactors, 2005, 25(1-4), 43-60. http://tcr.amegroups.com/article/view/5271/html
Reimann M-C, et al. Sphingosine-1-phosphate (S1P) in cancer immunity and development. Transl Cancer Res. 2015;4(5):460-8. http://tcr.amegroups.com/article/view/5271/html
Rodriguez et al. Sphingosine-1 phosphate: A new modulator of immune plasticity in the tumor microenvironment. Frontiers Oncol. 2016; 6:218.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066089/
Nakajima M, et al. The role of sphingosine-1-phosphate in the tumor microenvironment and its clinical implications. Tumor Biol. 2017;39(4): https://doi.org/10.1177/1010428317699133
Pyne NJ, et al. Sphingosine 1-phosphate and cancer. Adv Biol Regulat. 2018;68:97-106. https://doi.org/10.1016/j.jbior.2017.09.006
Olesh C. et al. S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion.J Clin Invest. 2020;130(10):5461-5476. https://doi.org/10.1172/JCI136928.
Tabasinezhad M et al. Sphingosin 1-phosphate contributes in tumor progression. Journal of cancer research and therapeutics. 2013;9(4):556-563.
Soo-Jin Parkand Dong-Soon Im. Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery. Biomol Ther (Seoul). 2017; 25(1): 80–90.
Galon J and Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197-218
Patel SA and Minn AJ. Combination cancer therapy with immune checkpoint blockade: Mechanisms and strategies. Immunity. 2018;48(3):417-33
Georgaki, S.; Skopeliti, M.; Tsiatas, M.; Nicolaou, K.A.; Ioannou, K.; Husband, A.; Bamias, A.; Dimopoulos, M.A.; Constantinou, A.I.; Tsitsilonis, O.E. Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo. J. Cell. Mol. Med., 2009, 13(9B), 3929-3938. http://dx.doi.org/10.1111/j.1582-4934.2009.00695.x PMID: 19220577
Yamazaki T et al. (2020) Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nature Immunol 21:1160-1171 https://doi.org/10.1038/s41590-020-0751-0
Miyamoto M et al (2018) Phenoxodiol increases cisplatin sensitivity in ovarian clear cancer cells through XIAP down-regulation and autophagy inhibition. Anticancer Res 38:301-306. doi: 10.21873/anticanres.12222

Anti-Inflammatory

Di Domizio, J., Gulen, M.F., Saidoune, F. et al. The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature (2022). https://doi.org/10.1038/s41586-022-04421-w
Zhao Q, Wei Y, et al. STING signalling promotes inflammation in experimental acute pancreatitis. 2018; 154(6): 1822-1835. DOI: 10.1053/j.gastro.2018.01.065
Benmerzoug S, Rose S, Bounab B, et al. STING-dependent sensing of self-DNA drives silica-induced lung inflammation. Nat Commun. 2018;9(1):5226. https://doi.org/10.1038/s41467-018-07425-1
Du S, Chen G, et al. DNA sensing and associated type 1 interferon signaling contributes to progression of radiation-induced liver injury. Cell Mol Immunol. 2020. https://doi.org/10.1038/s41423-020-0395-x
King KR, Aguirre AD, et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction. Nat Med. 2017; 23(12): 1481-1487. DOI: 10.1038/nm.4428
Motwani, Pesiridis S., and Fitzgerald K. A. DNA sensing by the cGAS–STING pathway in health and disease. Nature Reviews Genetics. 2019; 20 (657–674). DOI: 10.1038/s41576-019-0151-1
Maekawa H, Inoue T, Ouchi H, et al. Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury. Cell Rep. 2019;29(5):1261–1273. DOI: 10.1016/j.celrep.2019.09.050
Berthelot J-M, Drouet L and Liot E. Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway? Emerging Microbes &amp. 2020; Infections, 9:1, 1514-1522, DOI: 10.1080/22221751.2020.1785336
Berthelot J-M, and Liot E. COVID-19 as a STING disorder with delayed over-secretion of interferon-beta.. 2020 ; 56. https://doi.org/10.1016/j.ebiom.2020.102801
Deng X, Yu X, Pei Regulation of interferon production as a potential strategy for COVID-19 treatment. 2020. arXiv preprint arXiv:2003.00751
Kumari, N., Dwarakanath, B.S., Das, A. et al. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumor Biol. 37, 11553–11572 (2016). DOI: 10.1007/s13277-016-5098-7
Sheridan, C. Drug developers switch gears to inhibit STING. Nat Biotechnol 37, 199–201 (2019). https://doi.org/10.1038/s41587-019-0060-z
Yamazaki, T., Kirchmair, A., Sato, A. et al. Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nat Immunol 21, 1160–1171 (2020). https://doi.org/10.1038/s41590-020-0751-0
Jacquelot, N., Yamazaki, T., Roberti, M.P. et al. Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade. Cell Res 29, 846–861 (2019). https://doi.org/10.1038/s41422-019-0224-x
https://theconversation.com/blocking-the-deadly-cytokine-storm-is-a-vital-weapon-for-treating-covid-19-137690
https://www.outsourcing-pharma.com/Article/2020/10/13/First-COVID-19-patient-treated-in-Noxopharm-study
https://www.who.int/news-room/fact-sheets/detail/sepsis