Rehmadanta Sitepu
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摘要

近十年来,对热休克蛋白(HSP)活性抑制的抗癌候选物质的探索越来越多。一些HSP90候选抑制剂已进入第三期临床试验。然而,这一问题并没有紧随其后的是印尼HSP90抑制剂的研究,不仅对天然来源的研究,而且对合成候选物的研究。本研究旨在了解全球追踪HSP90候选抑制剂的发展情况,以便在印尼启动相关研究。对HSP90及其抑制剂的研究摘自2009年至2018年的科学文章。HSP90及其抑制剂在维持细胞存活的蛋白功能动态和稳定性方面具有重要价值。这也包括参与细胞增殖的癌基因蛋白,如酪氨酸激酶、转录因子和表达和相互作用依赖于HSP90的调节蛋白。转录因子p53、Alk基因、Wnt基因、糖皮质激素受体的表达也与HSP90蛋白活性有关。一些HSP90抑制剂的候选药物已经进入临床试验,如格尔达霉素类似物、间苯二酚衍生物和嘌呤类似物。天然来源的候选物质也正在开发中,如木犀草素、甘草查尔酮A、油尚醛、新生物素、没食子儿茶素没食子素、水飞蓟素、去胶素和萜类中的雷公藤红素、黄酮类中的芹菜素、姜黄素和甘黄酸。正在进入临床三期试验的HSP90抑制剂是间苯二酚衍生物的ganetespib和格尔达霉素类似物组的reaspimycin。从印尼自然资源中探索HSP90抑制剂,由于其作为抗癌候选物具有很高的影响价值,因此仍有很大的开发潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kajian Heat Shock Protein 90 (HSP90) dalam Pencarian Kandidat Penghambatnya melalui Ekplorasi Bahan Alam Indonesia
Exploration on anticancer candidates on inhibition of Heat Shock Protein (HSP) activity are increasing in the past ten years. Some of HSP90 inhibitor candidates were in third phase of clinical trials. However, this issue is not followed by the emergency of HSP90 inhibitor research in Indonesia, not only study on natural source but also on synthetic candidates. This study aims to look the development of tracking HSP90 inhibitor candidates globally so that it can initiate the related research in Indonesia. Study of HSP90 and its inhibitors were taken from scientific articles in the range from 2009 to 2018. HSP90 and its inhibitors have important values in the dynamics of functions and stability of proteins to maintain survival of cells. This also include the oncogene proteins that involve in cell proliferation such as tyrosine kinases, transcription factors, and regulatory proteins that expression and interaction depend on HSP90. Expression of the transcription factor p53, Alk gene, Wnt gene, glucocorticoid receptors have also links with HSP90 protein activity. Some candidates for inhibitor of HSP90 have been entering clinical trials such as geldanamycin analogues, resorcinol derivatives, and purines analog. Candidates from natural sources that are also being developed such as luteolin, licochalcone A, oleochantal, novobiocin, epigallocathecin gallat, silybin, deguelin, and celastrol from terpenoid class, Apigenin from flavon class, Curcumin, and  Gambogat Acid. HSP90 inhibitors which are entering the third phase of clinical trial are ganetespib from the resorcinol derivative and retaspimycin from geldanamisin analog group. Exploration of HSP90 inhibitors from Indonesia natural resources still have great potential to be developed because they have high impact values as anticancer candidates.
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