Ezatiostat hydrochloride for the treatment of myelodysplastic syndromes.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
University of Tennessee Health Science Center and West Cancer Center , 100 N. Humphreys Blvd., Memphis 38120, TN , USA +1 901 435 5570 ; +1 901 435 5595 ; dmahadevan@westclinic.com.
Daruka
D
Mahadevan
Gregory Ryan
GR
Sutton
D000818:Animals; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects
D004791:Enzyme Inhibitors; C096329:gamma-Glu-S-BzCys-PhGly diethyl ester; D005982:Glutathione Transferase; D005978:Glutathione
Jun N-terminal kinase inhibitor; ezatiostat (Telentra (R) TLK199); glutathione S-transferase pi antagonists and inhibitors; glutathione analogs and derivatives; myelodysplasia