Chiosis Gabriela, Tao Hui
Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
IDrugs. 2006 Nov;9(11):778-82.
Heat shock protein 90 (Hsp90) has emerged as an important target, the inhibition of which is aimed at a wide range of cell transformations that lead to malignancy. A clinical evaluation of 17-AAG, the first Hsp90 inhibitor to enter the clinic, revealed evidence of activity for the compound at a manageable level of toxicity. However, clinical results have also demonstrated the limitations of this drug. The identification of novel Hsp90 inhibitor classes with improved structural characteristics and better pharmacological profiles has therefore become a major focus of interest in the field of cancer therapeutics. This feature describes the purine-scaffold class of Hsp90 inhibitors, focusing on research efforts from the discovery stage to the clinical translation of such compounds.
热休克蛋白90（Hsp90）已成为一个重要靶点，对其进行抑制旨在针对多种导致恶性肿瘤的细胞转化。对首个进入临床的Hsp90抑制剂17-AAG进行的临床评估显示，该化合物在可控制的毒性水平下具有活性证据。然而，临床结果也证明了这种药物的局限性。因此，鉴定具有改善的结构特征和更好药理学特性的新型Hsp90抑制剂类别已成为癌症治疗领域的主要关注焦点。本专题介绍了Hsp90抑制剂的嘌呤骨架类别，重点关注此类化合物从发现阶段到临床转化的研究工作。
