Synthesis of Hsp90 inhibitor dimers as potential antitumor agents

被引：13

作者：

Muranaka, Kazuhiro ^{[1
]}

Sano, Akiko ^{[2
]}

Ichikawa, Satoshi ^{[1
]}

Matsuda, Akira ^{[1
]}

机构：

[1] Hokkaido Univ, Fac Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan

[2] Taiho Pharmaceut Co Ltd, Hanno Res Ctr, Discovery & Dev Lab 1, Hannou 3578527, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 11期

关键词：

heat shock protein; Hsp90; PU3; anticancer; structure-based drug design;

D O I：

10.1016/j.bmc.2008.04.070

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Structure-based drug design was used to systematically synthesize PU3-dimers. The cytotoxicity of PU3 dimers 6 against breast cancer cell lines was evaluated, and their potency increased as the length of the bridging linker increased. Among the compounds tested, 6e with a C-20 linker was the most potent and exhibited a 20- to 30-fold increase in activity compared with that of the parent compound 5. Western blot analyses of the cell lysates treated with 6c revealed that 6c resulted in the concentration-dependent degradation of the Hsp90 client protein Her2, which is consistent with other Hsp90 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5862 / 5870

页数：9

共 50 条

[31] Antitumor activity of MPC-3100, a synthetic Hsp90 inhibitor, in combination with erlotinib and sorafenib
Baichwal, Vijay R.
Brown, Brita
Wettstein, Daniel
Papac, Damon I.
Mather, Gary G.
Carlson, Robert O.
CANCER RESEARCH, 2011, 71
[32] Expressed as the sole Hsp90 of yeast, the α and β isoforms of human Hsp90 differ with regard to their capacities for activation of certain client proteins, whereas only Hsp90β generates sensitivity to the Hsp90 inhibitor radicicol
Millson, Stefan H.
Truman, Andrew W.
Racz, Attila
Hu, Bin
Panaretou, Barry
Nuttall, James
Mollapour, Mehdi
Soeti, Csaba
Piper, Peter W.
FEBS JOURNAL, 2007, 274 (17) : 4453 - 4463
[33] Targeting the Hsp90 Chaperone: Synthesis of Novel Resorcylic Acid Macrolactone Inhibitors of Hsp90
Day, James E. H.
Sharp, Swee Y.
Rowlands, Martin G.
Aherne, Wynne
Workman, Paul
Moody, Christopher J.
CHEMISTRY-A EUROPEAN JOURNAL, 2010, 16 (09) : 2758 - 2763
[34] Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors
Audisio, Davide
Methy-Gonnot, Delphine
Radanyi, Christine
Renoir, Jack-Michel
Denis, Stephanie
Sauvage, Felix
Vergnaud-Gauduchon, Juliette
Brion, Jean-Daniel
Messaoudi, Samir
Alami, Mouad
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 83 : 498 - 507
[35] Process improvements to the synthesis of BIIB028, a potent Hsp90 inhibitor
Walker, Donald G.
Humora, Michael J.
Kiesman, William F.
Joshi, Aarti
Clifford, Thomas
Chopade, Shubham
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2012, 244
[36] Maximizing the Therapeutic Potential of HSP90 Inhibitors
Butler, Lisa M.
Ferraldeschi, Roberta
Armstrong, Heather K.
Centenera, Margaret M.
Workman, Paul
MOLECULAR CANCER RESEARCH, 2015, 13 (11) : 1445 - 1451
[37] Hsp90 inhibitors as novel cancer chemotherapeutic agents
Neckers, L
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (04) : S55 - S61
[38] Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma
Chen, Ming-Huang
Chiang, Kun-Chun
Cheng, Chi-Tung
Huang, Shih-Chiang
Chen, Yeng-Yang
Chen, Tsung-Wen
Yeh, Ta-Sen
Jan, Yi-Yin
Wang, Hsi-Ming
Weng, Jiang-Jie
Chang, Peter Mu-Hsin
Liu, Chun-Yu
Li, Chung-Pin
Chao, Yee
Chen, Ming-Han
Huang, Chi-Ying F.
Yeh, Chun-Nan
ONCOTARGET, 2014, 5 (09) : 2372 - 2389
[39] Overview: Translating Hsp90 Biology into Hsp90 Drugs
Workman, Paul
CURRENT CANCER DRUG TARGETS, 2003, 3 (05) : 297 - 300
[40] Acquired resistance to HSP90 inhibitor and cancer progression
Chai, R. C. C.
Vieusseux, J. L.
Nguyen, C. H.
Lang, B. J.
Kouspou, M. M.
Price, J. T.
EJC SUPPLEMENTS, 2010, 8 (07): : 99 - 99

← 1 2 3 4 5 →