靶向热休克蛋白90：小分子抑制剂及其临床开发
Targeting Hsp90: small-molecule inhibitors and their clinical development.
作者信息
Taldone Tony, Gozman Alexander, Maharaj Ronnie, Chiosis Gabriela
机构信息
Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
出版信息
Curr Opin Pharmacol. 2008 Aug;8(4):370-4. doi: 10.1016/j.coph.2008.06.015. Epub 2008 Jul 31.
Abstract
The Hsp90 multichaperone complex has important roles in the development and progression of malignant transformation. Several small-molecule inhibitors of Hsp90 of diverse chemotypes have shown potent antitumor activity in a wide-range of malignancies, and are currently in clinical or late-stage preclinical investigation. This review intends to update the reader on advances made over the past two years in the clinical development of Hsp90 inhibitors in advanced cancers. It will refer to the two 17-AAG formulations, tanespimycin and IPI-504, and to synthetic small molecules, among which are the purine-scaffold Hsp90 inhibitor CNF2024/BIIB021, the isoxazole derivative VER-52296/NVP-AUY922, and the carbazol-4-one benzamide derivative SNX-5422, and will present our current knowledge on their clinical performance.
摘要
热休克蛋白90（Hsp90）多分子伴侣复合物在恶性转化的发生和发展过程中发挥着重要作用。几种具有不同化学类型的Hsp90小分子抑制剂在多种恶性肿瘤中均显示出强大的抗肿瘤活性，目前正处于临床或临床前后期研究阶段。本综述旨在向读者介绍过去两年中Hsp90抑制剂在晚期癌症临床开发方面取得的进展。文中将提及两种17-AAG制剂（坦螺旋霉素和IPI-504）以及合成小分子，其中包括嘌呤骨架的Hsp90抑制剂CNF2024/BIIB021、异恶唑衍生物VER-52296/NVP-AUY922和咔唑-4-酮苯甲酰胺衍生物SNX-5422，并将展示我们目前对它们临床性能的了解。
相似文献
1
Targeting Hsp90: small-molecule inhibitors and their clinical development.靶向热休克蛋白90：小分子抑制剂及其临床开发
Curr Opin Pharmacol. 2008 Aug;8(4):370-4. doi: 10.1016/j.coph.2008.06.015. Epub 2008 Jul 31.
2
Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.胶质母细胞瘤细胞对17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG，坦螺旋霉素）的获得性耐药
Cancer Res. 2009 Mar 1;69(5):1966-75. doi: 10.1158/0008-5472.CAN-08-3131. Epub 2009 Feb 24.
3
Evidence for efficacy of new Hsp90 inhibitors revealed by ex vivo culture of human prostate tumors.新的热休克蛋白 90 抑制剂的疗效证据来自人类前列腺肿瘤的体外培养。
Clin Cancer Res. 2012 Jul 1;18(13):3562-70. doi: 10.1158/1078-0432.CCR-12-0782. Epub 2012 May 9.
4
SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers.SNX2112是一种合成的热休克蛋白90抑制剂，对HER激酶依赖性癌症具有强大的抗肿瘤活性。
Clin Cancer Res. 2008 Jan 1;14(1):240-8. doi: 10.1158/1078-0432.CCR-07-1667.
5
BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90.BIIB021，一种口服可用的、完全合成的热休克蛋白Hsp90小分子抑制剂。
Mol Cancer Ther. 2009 Apr;8(4):921-9. doi: 10.1158/1535-7163.MCT-08-0758.
6
Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex.通过对热休克蛋白90（Hsp90）伴侣复合物的功能抑制，药物介导的多种蛋白质活性的靶向破坏。
Curr Med Chem. 2007;14(29):3122-38. doi: 10.2174/092986707782793925.
7
Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.小分子抑制剂筛选确定HSP90抑制剂17-AAG为胆囊癌的潜在治疗药物。
Oncotarget. 2017 Apr 18;8(16):26169-26184. doi: 10.18632/oncotarget.15410.
8
Discovery and development of heat shock protein 90 inhibitors as anticancer agents: a review of patented potent geldanamycin derivatives.热休克蛋白 90 抑制剂作为抗癌药物的发现和开发：专利强效格尔德霉素衍生物的综述。
Expert Opin Ther Pat. 2013 Aug;23(8):919-43. doi: 10.1517/13543776.2013.780597. Epub 2013 May 4.
9
Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90.17-烯丙基氨基-17-去甲氧基格尔德霉素对苯二酚盐酸盐（IPI-504）的研发，一种针对热休克蛋白90（Hsp90）的抗癌药物。
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17408-13. doi: 10.1073/pnas.0608372103. Epub 2006 Nov 7.
10
BIIB021, a novel Hsp90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy.BIIB021，一种新型的 HSP90 抑制剂，可增强头颈部鳞状细胞癌对放疗的敏感性。
Int J Cancer. 2010 Mar 1;126(5):1216-25. doi: 10.1002/ijc.24815.
引用本文的文献
1
Heat shock protein 90: biological functions, diseases, and therapeutic targets.热休克蛋白90：生物学功能、疾病及治疗靶点
MedComm (2020). 2024 Jan 25;5(2):e470. doi: 10.1002/mco2.470. eCollection 2024 Feb.
2
STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TβRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations.STA9090作为一种潜在的肝纤维化治疗药物：通过调节热休克蛋白90（HSP90）/转化生长因子β受体II（TβRII）/蛋白酶体相互作用获得的新见解：来自体外和体内研究的发现
Pharmaceuticals (Basel). 2023 Jul 28;16(8):1080. doi: 10.3390/ph16081080.
3
Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing.通过计算驱动的药物再利用鉴定治疗前列腺癌的有前途的候选药物。
Int J Mol Sci. 2023 Feb 5;24(4):3135. doi: 10.3390/ijms24043135.
4
Generation and characterization of a novel Knockout Model in Zebrafish.斑马鱼新型基因敲除模型的构建与鉴定
Front Cell Dev Biol. 2022 Oct 24;10:976111. doi: 10.3389/fcell.2022.976111. eCollection 2022.
5
Heterocyclic Compounds as Hsp90 Inhibitors: A Perspective on Anticancer Applications.作为Hsp90抑制剂的杂环化合物：抗癌应用前景
Pharmaceutics. 2022 Oct 18;14(10):2220. doi: 10.3390/pharmaceutics14102220.
6
The lonidamine derivative H2-gamendazole reduces cyst formation in polycystic kidney disease.Lonidamine 衍生物 H2-甘氨双唑可减少多囊肾病中的囊肿形成。
Am J Physiol Renal Physiol. 2022 Oct 1;323(4):F492-F506. doi: 10.1152/ajprenal.00095.2022. Epub 2022 Aug 18.
7
Novel Drugs with High Efficacy against Tumor Angiogenesis.新型高效抗肿瘤血管生成药物。
Int J Mol Sci. 2022 Jun 22;23(13):6934. doi: 10.3390/ijms23136934.
8
Heat shock protein 90 is a new potential target of anti-rejection therapy in allotransplantation.热休克蛋白 90 是同种异体移植中抗排斥治疗的一个新的潜在靶点。
Cell Stress Chaperones. 2022 Jul;27(4):337-351. doi: 10.1007/s12192-022-01272-2. Epub 2022 Apr 9.
9
NVP-AUY922 alleviates radiation-induced lung injury via inhibition of autophagy-dependent ferroptosis.NVP-AUY922通过抑制自噬依赖性铁死亡减轻辐射诱导的肺损伤。
Cell Death Discov. 2022 Feb 26;8(1):86. doi: 10.1038/s41420-022-00887-9.
10
Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90.3-(杂芳基)喹啉-2(1)-酮双杂环作为蛋白质折叠机制Hsp90潜在抑制剂的合成及生物活性
Molecules. 2022 Jan 9;27(2):412. doi: 10.3390/molecules27020412.
本文引用的文献
1
Discovery and development of purine-scaffold Hsp90 inhibitors.嘌呤骨架 Hsp90 抑制剂的发现与研制。
Expert Opin Drug Discov. 2008 Jan;3(1):99-114. doi: 10.1517/17460441.3.1.99.
2
NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis.NVP-AUY922：一种新型热休克蛋白90抑制剂，对异种移植肿瘤生长、血管生成和转移具有活性。
Cancer Res. 2008 Apr 15;68(8):2850-60. doi: 10.1158/0008-5472.CAN-07-5256.
3
BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors.黑色素瘤中的BRAF和NRAS突变：与HSP90抑制剂临床反应的潜在关系。
Mol Cancer Ther. 2008 Apr;7(4):737-9. doi: 10.1158/1535-7163.MCT-08-0145. Epub 2008 Mar 28.
4
Development and application of Hsp90 inhibitors.热休克蛋白90（Hsp90）抑制剂的研发与应用
Drug Discov Today. 2008 Jan;13(1-2):38-43. doi: 10.1016/j.drudis.2007.10.007. Epub 2007 Nov 26.
5
Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study.曲妥珠单抗与坦西莫司（17-AAG，KOS-953）联合应用于曲妥珠单抗难治性HER-2过表达乳腺癌患者安全且有效：一项I期剂量递增研究
J Clin Oncol. 2007 Dec 1;25(34):5410-7. doi: 10.1200/JCO.2007.11.7960.
6
Heat shock protein 90: a potential therapeutic target in leukemic progenitor and stem cells harboring mutant BCR-ABL resistant to kinase inhibitors.热休克蛋白90：携带对激酶抑制剂耐药的突变型BCR-ABL的白血病祖细胞和干细胞中的潜在治疗靶点。
Cell Cycle. 2007 Sep 15;6(18):2227-31. doi: 10.4161/cc.6.18.4722. Epub 2007 Jul 10.
7
FLT3 inhibition in acute myeloid leukaemia.急性髓系白血病中的FLT3抑制
Br J Haematol. 2007 Sep;138(6):687-99. doi: 10.1111/j.1365-2141.2007.06700.x. Epub 2007 Jul 26.
8
Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer.选择性化合物将Hsp90定义为小细胞肺癌中细胞凋亡的主要抑制剂。
Nat Chem Biol. 2007 Aug;3(8):498-507. doi: 10.1038/nchembio.2007.10. Epub 2007 Jul 1.
9
Heat shock protein 90: the cancer chaperone.热休克蛋白90：癌症伴侣蛋白
J Biosci. 2007 Apr;32(3):517-30. doi: 10.1007/s12038-007-0051-y.
10
Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress.靶向癌症伴侣蛋白HSP90：癌基因成瘾与肿瘤应激的联合治疗应用
Ann N Y Acad Sci. 2007 Oct;1113:202-16. doi: 10.1196/annals.1391.012. Epub 2007 May 18.
Zotero 插件