泰林特拉作为谷胱甘肽 S-转移酶 P 抑制剂的研发。
Development of Telintra as an Inhibitor of Glutathione S-Transferase P.
机构信息
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Department of Pathology and Laboratory Medicine, The University of Vermont, Burlington, VT, USA.
出版信息
Handb Exp Pharmacol. 2021;264:71-91. doi: 10.1007/164_2020_392.
Abstract
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.
摘要
谷胱甘肽 S-转移酶 P（GSTP）是提供细胞氧化还原平衡的一系列复杂途径的组成部分。它是某些肿瘤中的丰富蛋白质，在癌症耐药性中过度表达。它具有多种细胞功能，包括与小分子亲电试剂或蛋白质上易感性半胱氨酸残基的硫醇酶活性，以介导 S-谷胱甘肽化，以及与选择性蛋白激酶的伴侣结合。 GSTP 的纳摩尔抑制剂 TLK199（Telintra；Ezatiostat）的临床前和临床测试表明，该酶在造血中起作用，并且该药物对治疗骨髓增生异常综合征患者具有实用价值。
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