中文名 | Ezatiostat |
英文名 | (S)-ethyl 2-amino-5-(((R)-3-(benzylthio)-1-(((S)-2-ethoxy-2-oxo-1-phenylethyl)amino)-1-oxopropan-2-yl)amino)-5-oxopentanoate |
别名 | EZATIOSTAT游离 EZATIOSTAT游离的 GSTP1-1抑制剂(EZATIOSTAT) (S)-2-氨基-5-(((R)-3-(苄基硫基)-1-(((R)-2-乙氧基-2-氧代-1-苯乙基)氨基)-1-氧代丙烷-2-基)氨基)-5-氧代戊酸乙酯 |
英文别名 | CS-1110 TER 199 TLK-199 TELINTRA Ezatiostat Terrapin 199 (2R)-L-gamma-Glutamyl-S-(phenylmethyl)-L-cysteinyl-2-phenylglycine 1,3-diethyl ester Glycine, L-g-glutaMyl-S-(phenylMethyl)-L-cysteinyl-2-phenyl-,1,3-diethyl ester, (2R)- (S)-ETHYL 2-AMINO-5-((R)-3-(BENZYLTHIO)-1-((R)-2-ETHOXY-2-OXO-1-PHENYLETHYLAMINO)-1-OXOPROPAN-2-YLAMINO)-5-OXOPENTANOATE (S)-ethyl 2-amino-5-(((R)-3-(benzylthio)-1-(((S)-2-ethoxy-2-oxo-1-phenylethyl)amino)-1-oxopropan-2-yl)amino)-5-oxopentanoate |
CAS | 168682-53-9 |
化学式 | C27H35N3O6S |
分子量 | 529.65 |
密度 | 1.216±0.06 g/cm3(Predicted) |
熔点 | >94°C (dec.) |
沸点 | 749.7±60.0 °C(Predicted) |
溶解度 | DMSO (微溶) 、甲醇 (微溶) |
酸度系数 | 12?+-.0.46(Predicted) |
存储条件 | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C |
外观 | 固体 |
颜色 | White to Off-White |
靶点 | Glutathione S-transferase P1-1 (GSTP1) |
体外研究 | Ezatiostat causes dissociation of the enzyme from the jun-N-terminal kinase/c-Jun (JNK/JUN) complex, leading to JNK activation by phosphorylation. The therapeutic action of ezatiostat appears to include both proliferation of normal myeloid progenitors as well as apoptosis of the malignant clone. Selection of a resistant clone of an HL60 tumor cell line through chronic exposure to Ezatiostat (TLK199) results in cells with elevated activities of c-Jun NH2 terminal kinase (JNK1) and ERK1/ERK2, and allowes the cells to proliferate under stress conditions that induced high levels of apoptosis in the wild type cells. |
体内研究 | Administration of Ezatiostat (TLK199), stimulates both lymphocyte production and bone marrow progenitor (colony-forming unit-granulocyte macrophage) proliferation, but only in glutathione S-transferase P1-1 (GSTP1 +/+ ) and not in GSTP1 -/- animals. |
参考资料 展开查看 | 1: 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. doi: 10.1186/1756-8722-5-20. PubMed PMID: 22559819; PubMed Central PMCID: PMC3407785. 2: Raza A, Galili N, Mulford D, Smith SE, Brown GL, Steensma DP, Lyons RM, Boccia R, Sekeres MA, Garcia-Manero G, Mesa RA. Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS). J Hematol Oncol. 2012 Apr 30;5:18. doi: 10.1186/1756-8722-5-18. PubMed PMID: 22546242; PubMed Central PMCID: PMC3416694. 3: Lyons RM, Wilks ST, Young S, Brown GL. Oral ezatiostat HCl (Telintra®, TLK199) and idiopathic chronic neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. J Hematol Oncol. 2011 Nov 2;4:43. doi: 10.1186/1756-8722-4-43. PubMed PMID: 22047626; PubMed Central PMCID: PMC3235963. 4: Raza A, Galili N, Smith SE, Godwin J, Boccia RV, Myint H, Mahadevan D, Mulford D, Rarick M, Brown GL, Schaar D, Faderl S, Komrokji RS, List AF, Sekeres M. 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. doi: 10.1002/cncr.26469. Epub 2011 Sep 1. PubMed PMID: |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.888 ml | 9.44 ml | 18.88 ml |
5 mM | 0.378 ml | 1.888 ml | 3.776 ml |
10 mM | 0.189 ml | 0.944 ml | 1.888 ml |
5 mM | 0.038 ml | 0.189 ml | 0.378 ml |
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