NOV-002, a mimetic of glutathione disulfide

Abstract

Background: Oxidative signaling to modulate redox-sensitive cell functions is a heretofore unexploited approach to developing new drugs for poorly treated oncology indications, where current therapies are often only palliative and accompanied by severe toxicities. Objective: Clinical and non-clinical findings with NOV-002 (a mimetic of glutathione disulfide that represents such an approach) are reviewed and evaluated. Methods: Published data on NOV-002 along with unpublished information from the drug's sponsor were reviewed. Literature analysis also focused on protein S-glutathionylation as a regulatory mechanism, particularly in relation to cell signaling, proliferation and cytoskeletal architecture. Results/conclusion: NOV-002 is a mechanistically novel agent with potential for ameliorating hematologic toxicity and enhancing efficacy when used in combination with standard chemotherapy to treat cancer patients.

Keywords::

• biomarkers
• glutathione
• lung cancer
• redox
• S-glutathionylation
• thiols

Acknowledgements

The authors wish to acknowledge Georgy Moiseyvich Manichas of the St Petersburg City Oncological Dispensary and Yuri Nikolayevich Levashev and Sergey Vladimirovich Orlov of the State Research Center on Pulmonology of the Health Ministry of the Russian Federation, St Petersburg, for their pivotal roles in the conduct of the Phase II trial of NOV-002 in advanced non-small-cell lung cancer patients in Russia.

Notes