Ezatiostat hydrochloride for the treatment of myelodysplastic syndromes

Expert Opinion on Investigational Drugs
Daruka Mahadevan, Gregory Ryan Sutton

Abstract

Myelodysplastic syndromes (MDSs) are associated with significant morbidity due to ineffective hematopoiesis. Given the limited number of drugs approved by the FDA, there is a need for new therapeutic options. Ezatiostat is a novel agent targeting oxidative stress via inhibition of glutathione S-transferase 1. Herein, the authors summarize the standard of care in order to build the framework for therapeutic advancements. The purpose of this paper is to review the body of preclinical and clinical research literature on the investigational agent ezatiostat hydrochloride (TLK199) for the treatment of MDSs. The article includes details of the pathophysiology, pharmacology, toxicity and efficacy of ezatiostat hydrochloride from controlled studies in patients with myelodysplasia. MDS clonal heterogeneity and clonal architecture complexity has presented a significant technical challenge in developing effective therapies. Ezatiostat offers a unique and specific mechanism to improve the transfusion burden associated with myelodysplasia. Since it is tolerable as a monotherapy, combining ezatiostat with agents such as lenalidomide may have the most potential benefit.

References

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Citations

May 18, 2016·Cell Chemical Biology·Sharon M LouieDaniel K Nomura
Jul 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yoshiro NiitsuIrving Listowsky
Nov 7, 2019·Scientific Reports·Martín CancelaHenrique B Ferreira
Oct 23, 2020·Journal of Hematology & Oncology·Kecheng LeiKeqiang Ye
Jun 3, 2021·International Journal of Molecular Sciences·Jaewan JeonHae Yu Kim

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