生物活性

• 描述Myelodysplastic syndrome (MDS) is a clonal stem cell disorder resulting in bone marrow failure and variable cytopenias. While Glutathione S-transferase P1-1 (GSTpi) contributes to the regulation of cell proliferation. Ezatiostat, a tripeptide analog of glutathione, is a selective and orally active inhibitor of GSTP1-1 having the potential for MDS treatment. Ezatiostat causes dissociation of GSTP1-1 from the jun-N-terminal kinase/c-Jun (JNK/JUN) complex, leading to JNK activation by phosphorylation. Activated JNK phosphorylates c-JUN, which ultimately results in the stimulation of all myeloid lineages hematopoietic progenitor's proliferation and maturation^[3]. Chronic exposure of a resistant clone of an HL60 tumor cell line to ezatiostat resulted in elevated activities of c-Jun NH2 terminal kinase (JNK1) and ERK1/ERK2, and allowed the cells to proliferate under stress conditions that induced high levels of apoptosis in the wild type cells. In vivo, administration of ezatiostat stimulated both lymphocyte production and bone marrow progenitor proliferation^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00280631	Myelodysplastic Syndrome (MDS)	Phase 1 Phase 2	Completed	-	United States, Illinois ... more >> Loyola University Chicago-Cardinal Bernardin Cancer Center Maywood, Illinois, United States, 60153 Loyola University Medical Center Maywood, Illinois, United States, 60153 United States, Massachusetts University of Massachusetts (UMass) Memorial Medical Center Worcester, Massachusetts, United States, 01655 Collapse <<
  NCT00701870	Non-small Cell Lung Cancer	Phase 2	Terminated(Study TLK199.2102 w... more >>as terminated for lack of enrollment.) Collapse <<	-	United States, California ... more >> Central Hematology Oncology Medical Group Alhambra, California, United States, 91801 Pacific Cancer Medical Center, Inc. Anaheim, California, United States, 92801 Providence St. Joseph Medical Center Burbank, California, United States, 91505 St. Jude Heritage Healthcare Fullerton, California, United States, 92835 Wilshire Oncology Medical Group La Verne, California, United States, 91750 UCLA Medical Center Los Angeles, California, United States, 90095 Clinical Trials and Research Associates, Inc. Montebello, California, United States, 90640 North Valley Hematology/Oncology Medical Group Northridge, California, United States, 91325 Ventura County Hematology-Oncology Specialists Oxnard, California, United States, 93030 Samsum Clinic Santa Barbara, California, United States, 93105 Santa Barbara Hematology Oncology Medical Group, Inc. Santa Barbara, California, United States, 93105 Central Coast Medical Oncology Corporation Santa Maria, California, United States, 93454 United States, Florida Broward Oncology Associates Ft. Lauderdale, Florida, United States, 33308 Nature Coast Clinical Research Inverness, Florida, United States, 34452 Lakeland Regional Cancer Center Lakeland, Florida, United States, 33805 Florida Hospital Cancer Institute Ormand Beach, Florida, United States, 32174 United States, Georgia Suburban Hematology-Oncology Associates, PC Lawrenceville, Georgia, United States, 30045 United States, Illinois Medical & Surgical Specialists Galesburg, Illinois, United States, 61401 Joliet Oncology/Hematology Associates, Ltd. Joliet, Illinois, United States, 60435 United States, Nevada Comprehensive Cancer Centers of Nevada Henderson, Nevada, United States, 89052 United States, New York Montefiore Medical Center Bronx, New York, United States, 10467 United States, Ohio Case Medical Center-University Hospitals Cleveland, Ohio, United States, 44106 United States, Oklahoma The University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma, United States, 73104 United States, South Carolina Coastal Cancer Center Myrtle Beach, South Carolina, United States, 29572-4128 Collapse <<
  NCT00700206	Myelodysplastic Syndrome (MDS)	Phase 2	Completed	-	-

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• 参考文献

• [1] Galili N, Tamayo P, et al. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J Hematol Oncol. 2012 May 6;5:20.

  [2] Raza A, Galili N, et al. A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome. Cancer. 2012 Apr 15;118(8):2138-47.

  [3] Galili N, Tamayo P, Botvinnik OB, Mesirov JP, Brooks MR, Brown G, Raza A. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J Hematol Oncol. 2012 May 6;5:20

  [4] Ruscoe JE, Rosario LA, et al. Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferation pathways. J Pharmacol Exp Ther. 2001 Jul;298(1):339-45