Development of Telintra as an Inhibitor of Glutathione S-Transferase P.
Development of Telintra as an Inhibitor of Glutathione S-Transferase P.
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DOI：
10.1007/164_2020_392
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发表时间：
2021
影响因子：
--
通讯作者：
Tew KD
中科院分区：
文献类型：
--
作者：
Zhang J;Ye ZW;Janssen-Heininger Y;Townsend DM;Tew KD
谷胱甘肽S-转移酶P（GSTP）是提供细胞氧化还原稳态的一系列复杂途径的组分。它是某些肿瘤中丰富的蛋白质，在癌症耐药性中过度表达。它具有多种细胞功能，包括硫解酶活性，具有小的亲电子试剂或蛋白质上的敏感半胱氨酸残基以介导S-谷胱甘肽化，以及与选择的蛋白激酶结合的分子伴侣。GSTP的纳摩尔抑制剂TLK 199（Telintra; Ezatiostat）的临床前和临床测试表明了酶在造血中的作用以及药物在治疗骨髓增生异常综合征患者中的效用。
Glutathione S-transferase P (GSTP) is a component of a complex series of pathways that provide cellular redox homeostasis. It is an abundant protein in certain tumors and is over-expressed in cancer drug resistance. It has diverse cellular functions that include, thiolase activities with small electrophilic agents or susceptible cysteine residues on the protein to mediate S-glutathionylation, and chaperone binding with select protein kinases. Preclinical and clinical testing of a nanomolar inhibitor of GSTP, TLK199 (Telintra; Ezatiostat) has indicated a role for the enzyme in hematopoiesis and utility for the drug in the treatment of patients with myelodysplastic syndrome.