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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

Old and New Approaches to Target the Hsp90 Chaperone

Author(s): Jackee Sanchez, Trever R. Carter, Mark S. Cohen* and Brian S.J. Blagg

Volume 20, Issue 4, 2020

Page: [253 - 270] Pages: 18

DOI: 10.2174/1568009619666191202101330

Price: $65

Abstract

The 90-kDa heat shock protein (Hsp90) is a molecular chaperone that ensures cellular proteostasis by maintaining the folding, stabilization, activation, and degradation of over 400 client proteins. Hsp90 is not only critical for routine protein maintenance in healthy cells, but also during states of cellular stress, such as cancer and neurodegenerative diseases. Due to its ability to affect phosphorylation of numerous client proteins, inhibition of Hsp90 has been an attractive anticancer approach since the early 1990’s, when researchers identified a druggable target on the amino terminus of Hsp90 for a variety of cancers. Since then, 17 Hsp90 inhibitors that target the chaperone’s Nterminal domain, have entered clinical trials. None, however, have been approved thus far by the FDA as a cancer monotherapy. In these trials, a major limitation observed with Hsp90 inhibition at the N-terminal domain was dose-limiting toxicities and relatively poor pharmacokinetic profiles. Despite this, preclinical and clinical research continues to show that Hsp90 inhibitors effectively target cancer cell death and decrease tumor progression supporting the rationale for the development of novel Hsp90 inhibitors. Here, we present an in-depth overview of the Hsp90 inhibitors used in clinical trials. Finally, we present current shifts in the field related to targeting the carboxy-terminal domain of Hsp90 as well as to the development of isoform-selective inhibitors as a means to bypass the pitfalls of current Hsp90 inhibitors and improve clinical trial outcomes.

Keywords: Cancer, chaperones, geldanamycin, Grp94, Hsp90, novobiocin, TAS-116, TRAP1.

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[1]
Miyata, Y.; Nakamoto, H.; Neckers, L. The therapeutic target Hsp90 and cancer hallmarks. Curr. Pharm. Des., 2013, 19(3), 347-365.
[http://dx.doi.org/10.2174/138161213804143725] [PMID: 22920906]
[2]
Whitesell, L.; Lindquist, S.L. HSP90 and the chaperoning of cancer. Nat. Rev. Cancer, 2005, 5(10), 761-772.
[http://dx.doi.org/10.1038/nrc1716] [PMID: 16175177]
[3]
Ritossa, F.M. A new puffing pattern induced by temperature shock an DNP in Drosophila. Experientia, 1962, 18, 571-573.
[http://dx.doi.org/10.1007/BF02172188]
[4]
McKenzie, S.L.; Henikoff, S.; Meselson, M. Localization of RNA from heat-induced polysomes at puff sites in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, 1975, 72(3), 1117-1121.
[http://dx.doi.org/10.1073/pnas.72.3.1117] [PMID: 805422]
[5]
Ritossa, F.M. New puffs induced by temperature shock, DNP and salicilate in salivary chromosomes of D. melanogaster. Drosoph. Inf. Serv., 1963, 37, 122-123.
[6]
Ritossa, F.M. Experimental activation of specific loci in ploytene chromosomes of drosophila. Exp. Cell Res., 1964, 35, 601-607.
[http://dx.doi.org/10.1016/0014-4827(64)90147-8] [PMID: 14208747]
[7]
Tissières, A.; Mitchell, H.K.; Tracy, U.M. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J. Mol. Biol., 1974, 84(3), 389-398.
[http://dx.doi.org/10.1016/0022-2836(74)90447-1] [PMID: 4219221]
[8]
Bagatell, R.; Paine-Murrieta, G.D.; Taylor, C.W.; Pulcini, E.J.; Akinaga, S.; Benjamin, I.J.; Whitesell, L. Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of hsp90-binding agents. Clin. Cancer Res., 2000, 6(8), 3312-3318.
[PMID: 10955818]
[9]
Yufu, Y.; Nishimura, J.; Nawata, H. High constitutive expression of heat shock protein 90 alpha in human acute leukemia cells. Leuk. Res., 1992, 16(6-7), 597-605.
[http://dx.doi.org/10.1016/0145-2126(92)90008-U] [PMID: 1635378]
[10]
Prodromou, C. The ‘active life’ of Hsp90 complexes. Biochim. Biophys. Acta, 2012, 1823(3), 614-623.
[http://dx.doi.org/10.1016/j.bbamcr.2011.07.020] [PMID: 21840346]
[11]
Kamal, A.; Thao, L.; Sensintaffar, J.; Zhang, L.; Boehm, M.F.; Fritz, L.C.; Burrows, F.J. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature, 2003, 425(6956), 407-410.
[http://dx.doi.org/10.1038/nature01913] [PMID: 14508491]
[12]
Yano, M.; Naito, Z.; Tanaka, S.; Asano, G. Expression and roles of heat shock proteins in human breast cancer. Jpn. J. Cancer Res., 1996, 87(9), 908-915.
[http://dx.doi.org/10.1111/j.1349-7006.1996.tb02119.x] [PMID: 8878452]
[13]
Whitesell, L.; Mimnaugh, E.G.; De Costa, B.; Myers, C.E.; Neckers, L.M. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. USA, 1994, 91(18), 8324-8328.
[http://dx.doi.org/10.1073/pnas.91.18.8324] [PMID: 8078881]
[14]
Xu, Y.; Lindquist, S. Heat-shock protein hsp90 governs the activity of pp60v-src kinase. Proc. Natl. Acad. Sci. USA, 1993, 90(15), 7074-7078.
[http://dx.doi.org/10.1073/pnas.90.15.7074] [PMID: 7688470]
[15]
Xu, Y.; Singer, M.A.; Lindquist, S. Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proc. Natl. Acad. Sci. USA, 1999, 96(1), 109-114.
[http://dx.doi.org/10.1073/pnas.96.1.109] [PMID: 9874780]
[16]
Kim, Y.S.; Alarcon, S.V.; Lee, S.; Lee, M.J.; Giaccone, G.; Neckers, L.; Trepel, J.B. Update on Hsp90 inhibitors in clinical trial. Curr. Top. Med. Chem., 2009, 9(15), 1479-1492.
[http://dx.doi.org/10.2174/156802609789895728] [PMID: 19860730]
[17]
Schopf, F.H.; Biebl, M.M.; Buchner, J. The HSP90 chaperone machinery. Nat. Rev. Mol. Cell Biol., 2017, 18(6), 345-360.
[http://dx.doi.org/10.1038/nrm.2017.20] [PMID: 28429788]
[18]
Murphy, M.P.; LeVine, H., III Alzheimer’s disease and the amyloid-beta peptide. J. Alzheimers Dis., 2010, 19(1), 311-323.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[19]
Stefanis, L. α-Synuclein in Parkinson’s disease. Cold Spring Harb. Perspect. Med., 2012, 2(2)a009399
[http://dx.doi.org/10.1101/cshperspect.a009399] [PMID: 22355802]
[20]
Kalia, L.V.; Kalia, S.K. α-Synuclein and Lewy pathology in Parkinson’s disease. Curr. Opin. Neurol., 2015, 28(4), 375-381.
[http://dx.doi.org/10.1097/WCO.0000000000000215] [PMID: 26110807]
[21]
Csermely, P.; Schnaider, T.; Soti, C.; Prohászka, Z.; Nardai, G. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol. Ther., 1998, 79(2), 129-168.
[http://dx.doi.org/10.1016/S0163-7258(98)00013-8] [PMID: 9749880]
[22]
Sreedhar, A.S.; Kalmár, E.; Csermely, P.; Shen, Y.F. Hsp90 isoforms: functions, expression and clinical importance. FEBS Lett., 2004, 562(1-3), 11-15.
[http://dx.doi.org/10.1016/S0014-5793(04)00229-7] [PMID: 15069952]
[23]
Prodromou, C.; Roe, S.M.; O’Brien, R.; Ladbury, J.E.; Piper, P.W.; Pearl, L.H. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell, 1997, 90(1), 65-75.
[http://dx.doi.org/10.1016/S0092-8674(00)80314-1] [PMID: 9230303]
[24]
Meyer, P.; Prodromou, C.; Hu, B.; Vaughan, C.; Roe, S.M.; Panaretou, B.; Piper, P.W.; Pearl, L.H. Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol. Cell, 2003, 11(3), 647-658.
[http://dx.doi.org/10.1016/S1097-2765(03)00065-0] [PMID: 12667448]
[25]
Minami, Y.; Kimura, Y.; Kawasaki, H.; Suzuki, K.; Yahara, I. The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo. Mol. Cell. Biol., 1994, 14(2), 1459-1464.
[http://dx.doi.org/10.1128/MCB.14.2.1459] [PMID: 8289821]
[26]
Jhaveri, K.; Taldone, T.; Modi, S.; Chiosis, G. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim. Biophys. Acta, 2012, 1823(3), 742-755.
[http://dx.doi.org/10.1016/j.bbamcr.2011.10.008] [PMID: 22062686]
[27]
Yuno, A.; Lee, M.J.; Lee, S.; Tomita, Y.; Rekhtman, D.; Moore, B.; Trepel, J.B. Clinical evaluation and biomarker profiling of Hsp90 inhibitors. Methods Mol. Biol., 2018, 1709, 423-441.
[http://dx.doi.org/10.1007/978-1-4939-7477-1_29] [PMID: 29177675]
[28]
Garg, G.; Khandelwal, A.; Blagg, B.S. Anticancer inhibitors of Hsp90 function: Beyond the usual suspects. Adv. Cancer Res., 2016, 129, 51-88.
[http://dx.doi.org/10.1016/bs.acr.2015.12.001] [PMID: 26916001]
[29]
Blair, L.J.; Genest, O.; Mollapour, M. The multiple facets of the Hsp90 machine. Nat. Struct. Mol. Biol., 2019, 26(2), 92-95.
[http://dx.doi.org/10.1038/s41594-018-0177-7] [PMID: 30617298]
[30]
Soga, S.; Akinaga, S.; Shiotsu, Y. Hsp90 inhibitors as anti-cancer agents, from basic discoveries to clinical development. Curr. Pharm. Des., 2013, 19(3), 366-376.
[http://dx.doi.org/10.2174/138161213804143617] [PMID: 22920907]
[31]
Lee, B.L.; Rashid, S.; Wajda, B.; Wolmarans, A.; LaPointe, P.; Spyracopoulos, L. The Hsp90 chaperone: 1H and 19F dynamic nuclear magnetic resonance spectroscopy reveals a perfect enzyme. Biochemistry, 2019, 58(14), 1869-1877.
[http://dx.doi.org/10.1021/acs.biochem.9b00144] [PMID: 30869872]
[32]
Gorska, M.; Popowska, U.; Sielicka-Dudzin, A.; Kuban-Jankowska, A.; Sawczuk, W.; Knap, N.; Cicero, G.; Wozniak, F. Geldanamycin and its derivatives as Hsp90 inhibitors. Front. Biosci., 2012, 17, 2269-2277.
[http://dx.doi.org/10.2741/4050] [PMID: 22652777]
[33]
Huryn, D.M.; Wipf, P. Natural product chemistry and cancer drug discovery.Cancer Drug Des. Discov, 2nd ed; Neidle, S., Ed.; Academic Press: San Diego, 2014, pp. 91-120.
[http://dx.doi.org/10.1016/B978-0-12-396521-9.00003-6]
[34]
Biamonte, M.A.; Van de Water, R.; Arndt, J.W.; Scannevin, R.H.; Perret, D.; Lee, W.C. Heat shock protein 90: Inhibitors in clinical trials. J. Med. Chem., 2010, 53(1), 3-17.
[http://dx.doi.org/10.1021/jm9004708] [PMID: 20055425]
[35]
Samuni, Y.; Ishii, H.; Hyodo, F.; Samuni, U.; Krishna, M.C.; Goldstein, S.; Mitchell, J.B. Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs. Free Radic. Biol. Med., 2010, 48(11), 1559-1563.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.03.001] [PMID: 20211249]
[36]
Hanson, B.E.; Vesole, D.H. Retaspimycin hydrochloride (IPI-504): a novel heat shock protein inhibitor as an anticancer agent. Expert Opin. Investig. Drugs, 2009, 18(9), 1375-1383.
[http://dx.doi.org/10.1517/13543780903158934] [PMID: 19642950]
[37]
Lee, J. IPI-493, a potent, orally bioavailable Hsp90 inhibitor of the ansamycin class, in EORTC-NCI-AACR- International Conference, , 2008.Geneva, Switzerland.
[38]
Floris, G.; Sciot, R.; Wozniak, A.; Van Looy, T.; Wellens, J.; Faa, G.; Normant, E.; Debiec-Rychter, M.; Schöffski, P. The novel HSP90 inhibitor, IPI-493, is highly effective in human gastrostrointestinal stromal tumor xenografts carrying heterogeneous KIT mutations. Clin. Cancer Res., 2011, 17(17), 5604-5614.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0562] [PMID: 21737509]
[39]
Chène, P. ATPases as drug targets: Learning from their structure. Nat. Rev. Drug Discov., 2002, 1(9), 665-673.
[http://dx.doi.org/10.1038/nrd894] [PMID: 12209147]
[40]
Chiosis, G.; Timaul, M.N.; Lucas, B.; Munster, P.N.; Zheng, F.F.; Sepp-Lorenzino, L.; Rosen, N. A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem. Biol., 2001, 8(3), 289-299.
[http://dx.doi.org/10.1016/S1074-5521(01)00015-1] [PMID: 11306353]
[41]
Wright, L.; Barril, X.; Dymock, B.; Sheridan, L.; Surgenor, A.; Beswick, M.; Drysdale, M.; Collier, A.; Massey, A.; Davies, N.; Fink, A.; Fromont, C.; Aherne, W.; Boxall, K.; Sharp, S.; Workman, P.; Hubbard, R.E. Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms. Chem. Biol., 2004, 11(6), 775-785.
[http://dx.doi.org/10.1016/j.chembiol.2004.03.033] [PMID: 15217611]
[42]
Lundgren, K.; Zhang, H.; Brekken, J.; Huser, N.; Powell, R.E.; Timple, N.; Busch, D.J.; Neely, L.; Sensintaffar, J.L.; Yang, Y.C.; McKenzie, A.; Friedman, J.; Scannevin, R.; Kamal, A.; Hong, K.; Kasibhatla, S.R.; Boehm, M.F.; Burrows, F.J. BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Mol. Cancer Ther., 2009, 8(4), 921-929.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0758] [PMID: 19372565]
[43]
Lundgren, K.; Biamonte, M.A. CHAPTER 5 The Discovery of BIIB021 and BIIB028., 2014, 158-179.
[44]
Shi, X.; Kiesman, W.F.; Walker, D.G. Development of Hsp90 Inhibitors for the Treatment of HER-2 Positive Solid Cancers, in Comprehensive Accounts of Pharmaceutical Research and Development: From Discovery to Late-Stage Process Development. Am. Chem. Soc, 2016, 1, 69-100.
[http://dx.doi.org/10.1021/bk-2016-1239.ch003]
[45]
Caldas-Lopes, E.; Cerchietti, L.; Ahn, J.H.; Clement, C.C.; Robles, A.I.; Rodina, A.; Moulick, K.; Taldone, T.; Gozman, A.; Guo, Y.; Wu, N.; de Stanchina, E.; White, J.; Gross, S.S.; Ma, Y.; Varticovski, L.; Melnick, A.; Chiosis, G. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc. Natl. Acad. Sci. USA, 2009, 106(20), 8368-8373.
[http://dx.doi.org/10.1073/pnas.0903392106] [PMID: 19416831]
[46]
Fadden, P.; Huang, K.H.; Veal, J.M.; Steed, P.M.; Barabasz, A.F.; Foley, B.; Hu, M.; Partridge, J.M.; Rice, J.; Scott, A.; Dubois, L.G.; Freed, T.A.; Silinski, M.A.; Barta, T.E.; Hughes, P.F.; Ommen, A.; Ma, W.; Smith, E.D.; Spangenberg, A.W.; Eaves, J.; Hanson, G.J.; Hinkley, L.; Jenks, M.; Lewis, M.; Otto, J.; Pronk, G.J.; Verleysen, K.; Haystead, T.A.; Hall, S.E. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem. Biol., 2010, 17(7), 686-694.
[http://dx.doi.org/10.1016/j.chembiol.2010.04.015] [PMID: 20659681]
[47]
Huang, K.H.; Veal, J.M.; Fadden, R.P.; Rice, J.W.; Eaves, J.; Strachan, J.P.; Barabasz, A.F.; Foley, B.E.; Barta, T.E.; Ma, W.; Silinski, M.A.; Hu, M.; Partridge, J.M.; Scott, A.; DuBois, L.G.; Freed, T.; Steed, P.M.; Ommen, A.J.; Smith, E.D.; Hughes, P.F.; Woodward, A.R.; Hanson, G.J.; McCall, W.S.; Markworth, C.J.; Hinkley, L.; Jenks, M.; Geng, L.; Lewis, M.; Otto, J.; Pronk, B.; Verleysen, K.; Hall, S.E. Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents. J. Med. Chem., 2009, 52(14), 4288-4305.
[http://dx.doi.org/10.1021/jm900230j] [PMID: 19552433]
[48]
Cheung, K.M.; Matthews, T.P.; James, K.; Rowlands, M.G.; Boxall, K.J.; Sharp, S.Y.; Maloney, A.; Roe, S.M.; Prodromou, C.; Pearl, L.H.; Aherne, G.W.; McDonald, E.; Workman, P. The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(14), 3338-3343.
[http://dx.doi.org/10.1016/j.bmcl.2005.05.046] [PMID: 15955698]
[49]
Brough, P.A.; Aherne, W.; Barril, X.; Borgognoni, J.; Boxall, K.; Cansfield, J.E.; Cheung, K.M.; Collins, I.; Davies, N.G.; Drysdale, M.J.; Dymock, B.; Eccles, S.A.; Finch, H.; Fink, A.; Hayes, A.; Howes, R.; Hubbard, R.E.; James, K.; Jordan, A.M.; Lockie, A.; Martins, V.; Massey, A.; Matthews, T.P.; McDonald, E.; Northfield, C.J.; Pearl, L.H.; Prodromou, C.; Ray, S.; Raynaud, F.I.; Roughley, S.D.; Sharp, S.Y.; Surgenor, A.; Walmsley, D.L.; Webb, P.; Wood, M.; Workman, P.; Wright, L. 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J. Med. Chem., 2008, 51(2), 196-218.
[http://dx.doi.org/10.1021/jm701018h] [PMID: 18020435]
[50]
Eccles, S.A.; Massey, A.; Raynaud, F.I.; Sharp, S.Y.; Box, G.; Valenti, M.; Patterson, L.; de Haven Brandon, A.; Gowan, S.; Boxall, F.; Aherne, W.; Rowlands, M.; Hayes, A.; Martins, V.; Urban, F.; Boxall, K.; Prodromou, C.; Pearl, L.; James, K.; Matthews, T.P.; Cheung, K.M.; Kalusa, A.; Jones, K.; McDonald, E.; Barril, X.; Brough, P.A.; Cansfield, J.E.; Dymock, B.; Drysdale, M.J.; Finch, H.; Howes, R.; Hubbard, R.E.; Surgenor, A.; Webb, P.; Wood, M.; Wright, L.; Workman, P. NVP-AUY922: A novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res., 2008, 68(8), 2850-2860.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5256] [PMID: 18413753]
[51]
Jensen, M.R.; Schoepfer, J.; Radimerski, T.; Massey, A.; Guy, C.T.; Brueggen, J.; Quadt, C.; Buckler, A.; Cozens, R.; Drysdale, M.J.; Garcia-Echeverria, C.; Chène, P. NVP-AUY922: A small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Res., 2008, 10(2), R33.
[http://dx.doi.org/10.1186/bcr1996] [PMID: 18430202]
[52]
Wang, Y.; Trepel, J.B.; Neckers, L.M.; Giaccone, G. STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. Curr. Opin. Investig. Drugs, 2010, 11(12), 1466-1476.
[PMID: 21154128]
[53]
Woodhead, A.J.; Angove, H.; Carr, M.G.; Chessari, G.; Congreve, M.; Coyle, J.E.; Cosme, J.; Graham, B.; Day, P.J.; Downham, R.; Fazal, L.; Feltell, R.; Figueroa, E.; Frederickson, M.; Lewis, J.; McMenamin, R.; Murray, C.W.; O’Brien, M.A.; Parra, L.; Patel, S.; Phillips, T.; Rees, D.C.; Rich, S.; Smith, D.M.; Trewartha, G.; Vinkovic, M.; Williams, B.; Woolford, A.J. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J. Med. Chem., 2010, 53(16), 5956-5969.
[http://dx.doi.org/10.1021/jm100060b] [PMID: 20662534]
[54]
Murray, C.W.; Carr, M.G.; Callaghan, O.; Chessari, G.; Congreve, M.; Cowan, S.; Coyle, J.E.; Downham, R.; Figueroa, E.; Frederickson, M.; Graham, B.; McMenamin, R.; O’Brien, M.A.; Patel, S.; Phillips, T.R.; Williams, G.; Woodhead, A.J.; Woolford, A.J. Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency. J. Med. Chem., 2010, 53(16), 5942-5955.
[http://dx.doi.org/10.1021/jm100059d] [PMID: 20718493]
[55]
Nakashima, T.; Ishii, T.; Tagaya, H.; Seike, T.; Nakagawa, H.; Kanda, Y.; Akinaga, S.; Soga, S.; Shiotsu, Y. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin. Cancer Res., 2010, 16(10), 2792-2802.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-3112] [PMID: 20406843]
[56]
Cavenagh, J.; Oakervee, H.; Baetiong-Caguioa, P.; Davies, F.; Gharibo, M.; Rabin, N.; Kurman, M.; Novak, B.; Shiraishi, N.; Nakashima, D.; Akinaga, S.; Yong, K. A phase I/II study of KW-2478, an Hsp90 inhibitor, in combination with bortezomib in patients with relapsed/refractory multiple myeloma. Br. J. Cancer, 2017, 117(9), 1295-1302.
[http://dx.doi.org/10.1038/bjc.2017.302] [PMID: 28873084]
[57]
Bussenius, J.; Blazey, C.M.; Aay, N.; Anand, N.K.; Arcalas, A.; Baik, T.; Bowles, O.J.; Buhr, C.A.; Costanzo, S.; Curtis, J.K.; DeFina, S.C.; Dubenko, L.; Heuer, T.S.; Huang, P.; Jaeger, C.; Joshi, A.; Kennedy, A.R.; Kim, A.I.; Lara, K.; Lee, J.; Li, J.; Lougheed, J.C.; Ma, S.; Malek, S.; Manalo, J.C.; Martini, J.F.; McGrath, G.; Nicoll, M.; Nuss, J.M.; Pack, M.; Peto, C.J.; Tsang, T.H.; Wang, L.; Womble, S.W.; Yakes, M.; Zhang, W.; Rice, K.D. Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90. Bioorg. Med. Chem. Lett., 2012, 22(17), 5396-5404.
[http://dx.doi.org/10.1016/j.bmcl.2012.07.052] [PMID: 22877636]
[58]
Haarberg, H.E.; Paraiso, K.H.; Wood, E.; Rebecca, V.W.; Sondak, V.K.; Koomen, J.M.; Smalley, K.S. Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Mol. Cancer Ther., 2013, 12(6), 901-912.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-1003] [PMID: 23538902]
[59]
Menezes, D.L.; Taverna, P.; Jensen, M.R.; Abrams, T.; Stuart, D.; Yu, G.K.; Duhl, D.; Machajewski, T.; Sellers, W.R.; Pryer, N.K.; Gao, Z. The novel oral Hsp90 inhibitor NVP-HSP990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo. Mol. Cancer Ther., 2012, 11(3), 730-739.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0667] [PMID: 22246440]
[60]
Ohkubo, S.; Kodama, Y.; Muraoka, H.; Hitotsumachi, H.; Yoshimura, C.; Kitade, M.; Hashimoto, A.; Ito, K.; Gomori, A.; Takahashi, K.; Shibata, Y.; Kanoh, A.; Yonekura, K. TAS-116, a highly selective inhibitor of heat shock protein 90α and β, demonstrates potent antitumor activity and minimal ocular toxicity in preclinical models. Mol. Cancer Ther., 2015, 14(1), 14-22.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0219] [PMID: 25416789]
[61]
Shimomura, A.; Yamamoto, N.; Kondo, S.; Fujiwara, Y.; Suzuki, S.; Yanagitani, N.; Horiike, A.; Kitazono, S.; Ohyanagi, F.; Doi, T.; Kuboki, Y.; Kawazoe, A.; Shitara, K.; Ohno, I.; Banerji, U.; Sundar, R.; Ohkubo, S.; Calleja, E.M.; Nishio, M. First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in patients with advanced solid tumors. Mol. Cancer Ther., 2019, 18(3), 531-540.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0831] [PMID: 30679388]
[62]
Kurokawa, Y. Phase II study of TAS-116, on oral inhibitor of heat shock protein (HSP90), in metastatic or unresectable gastrointestinal stromal tumor refractory to imatinib, sunitinib, and regorafenib, in ESMO 2017 Congress.,, Annals of OncologyMadrid, Spain. 2017, pp. v521-v538.
[63]
Söti, C.; Rácz, A.; Csermely, P. A Nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J. Biol. Chem., 2002, 277(9), 7066-7075.
[http://dx.doi.org/10.1074/jbc.M105568200] [PMID: 11751878]
[64]
Donnelly, A.; Blagg, B.S. Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket. Curr. Med. Chem., 2008, 15(26), 2702-2717.
[http://dx.doi.org/10.2174/092986708786242895] [PMID: 18991631]
[65]
Schulte, T.W.; Akinaga, S.; Soga, S.; Sullivan, W.; Stensgard, B.; Toft, D.; Neckers, L.M. Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones, 1998, 3(2), 100-108.
[http://dx.doi.org/10.1379/1466-1268(1998)003<0100:ARBTTN>2.3.CO;2] [PMID: 9672245]
[66]
Yun, B.G.; Huang, W.; Leach, N.; Hartson, S.D.; Matts, R.L. Novobiocin induces a distinct conformation of Hsp90 and alters Hsp90-cochaperone-client interactions. Biochemistry, 2004, 43(25), 8217-8229.
[http://dx.doi.org/10.1021/bi0497998] [PMID: 15209518]
[67]
Marcu, M.G.; Chadli, A.; Bouhouche, I.; Catelli, M.; Neckers, L.M. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J. Biol. Chem., 2000, 275(47), 37181-37186.
[http://dx.doi.org/10.1074/jbc.M003701200] [PMID: 10945979]
[68]
Chatterjee, B.K.; Jayaraj, A.; Kumar, V.; Blagg, B.; Davis, R.E.; Jayaram, B.; Deep, S.; Chaudhuri, T.K. Stimulation of heat shock protein 90 chaperone function through binding of a novobiocin analog KU-32. J. Biol. Chem., 2019, 294(16), 6450-6467.
[http://dx.doi.org/10.1074/jbc.RA118.002502] [PMID: 30792306]
[69]
Rahimi, M.N.; McAlpine, S.R. Protein-protein inhibitor designed de novo to target the MEEVD region on the C-terminus of Hsp90 and block co-chaperone activity. Chem. Commun. (Camb.), 2019, 55(6), 846-849.
[http://dx.doi.org/10.1039/C8CC07576J] [PMID: 30575826]
[70]
Terracciano, S.; Russo, A.; Chini, M.G.; Vaccaro, M.C.; Potenza, M.; Vassallo, A.; Riccio, R.; Bifulco, G.; Bruno, I. Discovery of new molecular entities able to strongly interfere with Hsp90 C-terminal domain. Sci. Rep., 2018, 8(1), 1709.
[http://dx.doi.org/10.1038/s41598-017-14902-y] [PMID: 29374167]
[71]
Cox, M.B.; Miller, C.A. III cooperation of heat shock protein 90 and p23 in aryl hydrocarbon receptor signaling. Cell Stress Chaperones, 2004, 9(1), 4-20.
[http://dx.doi.org/10.1379/1466-1268(2004)009<0004:COHSPA>2.0.CO;2] [PMID: 15270073]
[72]
Zhao, J.; Zhao, H.; Hall, J.A.; Brown, D.; Brandes, E.; Bazzill, J.; Grogan, P.T.; Subramanian, C.; Vielhauer, G.; Cohen, M.S.; Blagg, B.S. Triazole containing novobiocin and biphenyl amides as Hsp90 C-terminal inhibitors. MedChemComm, 2014, 5(9), 1317-1323.
[http://dx.doi.org/10.1039/C4MD00102H] [PMID: 25328661]
[73]
White, P.T.; Subramanian, C.; Zhu, Q.; Zhang, H.; Zhao, H.; Gallagher, R.; Timmermann, B.N.; Blagg, B.S.; Cohen, M.S. Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. Surgery, 2016, 159(1), 142-151.
[http://dx.doi.org/10.1016/j.surg.2015.07.050] [PMID: 26542767]
[74]
Subramanian, C.; Kovatch, K.J.; Sim, M.W.; Wang, G.; Prince, M.E.; Carey, T.E.; Davis, R.; Blagg, B.S.J.; Cohen, M.S. Novel C-terminal heat shock protein 90 inhibitors (KU711 and Ku757) are effective in targeting head and neck squamous cell carcinoma cancer stem cells. Neoplasia, 2017, 19(12), 1003-1011.
[http://dx.doi.org/10.1016/j.neo.2017.09.003] [PMID: 29121598]
[75]
Samadi, A.K.; Zhang, X.; Mukerji, R.; Donnelly, A.C.; Blagg, B.S.; Cohen, M.S. A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells. Cancer Lett., 2011, 312(2), 158-167.
[http://dx.doi.org/10.1016/j.canlet.2011.07.031] [PMID: 21924824]
[76]
Cohen, S.M.; Mukerji, R.; Samadi, A.K.; Zhang, X.; Zhao, H.; Blagg, B.S.; Cohen, M.S. Novel C-terminal Hsp90 inhibitor for head and neck squamous cell cancer (HNSCC) with in vivo efficacy and improved toxicity profiles compared with standard agents. Ann. Surg. Oncol., 2012, 19(Suppl. 3), S483-S490.
[http://dx.doi.org/10.1245/s10434-011-1971-1] [PMID: 21837531]
[77]
Byrd, K.M.; Subramanian, C.; Sanchez, J.; Motiwala, H.F.; Liu, W.; Cohen, M.S.; Holzbeierlein, J.; Blagg, B.S. Synthesis and biological evaluation of novobiocin core analogues as Hsp90 inhibitors. Chemistry, 2016, 22(20), 6921-6931.
[http://dx.doi.org/10.1002/chem.201504955] [PMID: 27037933]
[78]
Langer, T.; Rosmus, S.; Fasold, H. Intracellular localization of the 90 kDA heat shock protein (HSP90alpha) determined by expression of a EGFP-HSP90alpha-fusion protein in unstressed and heat stressed 3T3 cells. Cell Biol. Int., 2003, 27(1), 47-52.
[http://dx.doi.org/10.1016/S1065-6995(02)00256-1] [PMID: 12713799]
[79]
Condelli, V.; Crispo, F.; Pietrafesa, M.; Lettini, G.; Matassa, D.S.; Esposito, F.; Landriscina, M.; Maddalena, F. HSP90 molecular chaperones, metabolic rewiring, and epigenetics: Impact on tumor progression and perspective for anticancer therapy. Cells, 2019, 8(6), E532
[http://dx.doi.org/10.3390/cells8060532] [PMID: 31163702]
[80]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[81]
Li, W.; Sahu, D.; Tsen, F. Secreted heat shock protein-90 (Hsp90) in wound healing and cancer. Biochim. Biophys. Acta, 2012, 1823(3), 730-741.
[http://dx.doi.org/10.1016/j.bbamcr.2011.09.009] [PMID: 21982864]
[82]
Marzec, M.; Eletto, D.; Argon, Y. GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum. Biochim. Biophys. Acta, 2012, 1823(3), 774-787.
[http://dx.doi.org/10.1016/j.bbamcr.2011.10.013] [PMID: 22079671]
[83]
Eletto, D.; Dersh, D.; Argon, Y. GRP94 in ER quality control and stress responses. Semin. Cell Dev. Biol., 2010, 21(5), 479-485.
[http://dx.doi.org/10.1016/j.semcdb.2010.03.004] [PMID: 20223290]
[84]
Van, P.N.; Peter, F.; Söling, H.D. Four intracisternal calcium-binding glycoproteins from rat liver microsomes with high affinity for calcium. No indication for calsequestrin-like proteins in inositol 1,4,5-trisphosphate-sensitive calcium sequestering rat liver vesicles. J. Biol. Chem., 1989, 264(29), 17494-17501.
[PMID: 2793869]
[85]
Biswas, C.; Ostrovsky, O.; Makarewich, C.A.; Wanderling, S.; Gidalevitz, T.; Argon, Y. The peptide-binding activity of GRP94 is regulated by calcium. Biochem. J., 2007, 405(2), 233-241.
[http://dx.doi.org/10.1042/BJ20061867] [PMID: 17411420]
[86]
Felts, S.J.; Owen, B.A.; Nguyen, P.; Trepel, J.; Donner, D.B.; Toft, D.O. The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties. J. Biol. Chem., 2000, 275(5), 3305-3312.
[http://dx.doi.org/10.1074/jbc.275.5.3305] [PMID: 10652318]
[87]
Song, H.Y.; Dunbar, J.D.; Zhang, Y.X.; Guo, D.; Donner, D.B. Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. J. Biol. Chem., 1995, 270(8), 3574-3581.
[http://dx.doi.org/10.1074/jbc.270.8.3574] [PMID: 7876093]
[88]
Hua, G.; Zhang, Q.; Fan, Z. Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. J. Biol. Chem., 2007, 282(28), 20553-20560.
[http://dx.doi.org/10.1074/jbc.M703196200] [PMID: 17513296]
[89]
Sciacovelli, M.; Guzzo, G.; Morello, V.; Frezza, C.; Zheng, L.; Nannini, N.; Calabrese, F.; Laudiero, G.; Esposito, F.; Landriscina, M.; Defilippi, P.; Bernardi, P.; Rasola, A. The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase. Cell Metab., 2013, 17(6), 988-999.
[http://dx.doi.org/10.1016/j.cmet.2013.04.019] [PMID: 23747254]
[90]
Masgras, I.; Sanchez-Martin, C.; Colombo, G.; Rasola, A. The Chaperone TRAP1 as a modulator of the mitochondrial adaptations in cancer cells. Front. Oncol., 2017, 7, 58.
[http://dx.doi.org/10.3389/fonc.2017.00058] [PMID: 28405578]
[91]
Xiang, F.; Ma, S.Y.; Lv, Y.L.; Zhang, D.X.; Song, H.P.; Huang, Y.S. Tumor necrosis factor receptor-associated protein 1 regulates hypoxia-induced apoptosis through a mitochondria-dependent pathway mediated by cytochrome c oxidase subunit II. Burns Trauma, 2019, 7, 16.
[http://dx.doi.org/10.1186/s41038-019-0154-3] [PMID: 31143823]
[92]
Grbovic, O.M.; Basso, A.D.; Sawai, A.; Ye, Q.; Friedlander, P.; Solit, D.; Rosen, N. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc. Natl. Acad. Sci. USA, 2006, 103(1), 57-62.
[http://dx.doi.org/10.1073/pnas.0609973103] [PMID: 16371460]
[93]
Evans, C.G.; Wisén, S.; Gestwicki, J.E. Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. J. Biol. Chem., 2006, 281(44), 33182-33191.
[http://dx.doi.org/10.1074/jbc.M606192200] [PMID: 16973602]
[94]
Dickey, C.A.; Kamal, A.; Lundgren, K.; Klosak, N.; Bailey, R.M.; Dunmore, J.; Ash, P.; Shoraka, S.; Zlatkovic, J.; Eckman, C.B.; Patterson, C.; Dickson, D.W.; Nahman, N.S., Jr; Hutton, M.; Burrows, F.; Petrucelli, L. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J. Clin. Invest., 2007, 117(3), 648-658.
[http://dx.doi.org/10.1172/JCI29715] [PMID: 17304350]
[95]
Robert, J.; Ménoret, A.; Cohen, N. Cell surface expression of the endoplasmic reticular heat shock protein gp96 is phylogenetically conserved. J. Immunol., 1999, 163(8), 4133-4139.
[PMID: 10510348]
[96]
Ansa-Addo, E.A.; Thaxton, J.; Hong, F.; Wu, B.X.; Zhang, Y.; Fugle, C.W.; Metelli, A.; Riesenberg, B.; Williams, K.; Gewirth, D.T.; Chiosis, G.; Liu, B.; Li, Z. Clients and oncogenic roles of molecular chaperone gp96/grp94. Curr. Top. Med. Chem., 2016, 16(25), 2765-2778.
[http://dx.doi.org/10.2174/1568026616666160413141613] [PMID: 27072698]
[97]
Amoroso, M.R.; Matassa, D.S.; Sisinni, L.; Lettini, G.; Landriscina, M.; Esposito, F. TRAP1 revisited: novel localizations and functions of a ‘next-generation’ biomarker. (review). Int. J. Oncol., 2014, 45(3), 969-977.
[http://dx.doi.org/10.3892/ijo.2014.2530] [PMID: 24990602]
[98]
Renouf, D.J.; Velazquez-Martin, J.P.; Simpson, R.; Siu, L.L.; Bedard, P.L. Ocular toxicity of targeted therapies. J. Clin. Oncol., 2012, 30(26), 3277-3286.
[http://dx.doi.org/10.1200/JCO.2011.41.5851] [PMID: 22649132]
[99]
Peterson, L.B.; Eskew, J.D.; Vielhauer, G.A.; Blagg, B.S. The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking. Mol. Pharm., 2012, 9(6), 1841-1846.
[http://dx.doi.org/10.1021/mp300138n] [PMID: 22554505]
[100]
Neckers, L.; Workman, P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin. Cancer Res., 2012, 18(1), 64-76.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1000] [PMID: 22215907]
[101]
Rosser, M.F.; Nicchitta, C.V. Ligand interactions in the adenosine nucleotide-binding domain of the Hsp90 chaperone, GRP94. I. Evidence for allosteric regulation of ligand binding. J. Biol. Chem., 2000, 275(30), 22798-22805.
[http://dx.doi.org/10.1074/jbc.M001477200] [PMID: 10816561]
[102]
Wang, M.; Shen, G.; Blagg, B.S. Radanamycin, a macrocyclic chimera of radicicol and geldanamycin. Bioorg. Med. Chem. Lett., 2006, 16(9), 2459-2462.
[http://dx.doi.org/10.1016/j.bmcl.2006.01.086] [PMID: 16464590]
[103]
Shen, G.; Blagg, B.S. Radester, a novel inhibitor of the Hsp90 protein folding machinery. Org. Lett., 2005, 7(11), 2157-2160.
[http://dx.doi.org/10.1021/ol050580a] [PMID: 15901158]
[104]
Duerfeldt, A.S.; Brandt, G.E.; Blagg, B.S. Design, synthesis, and biological evaluation of conformationally constrained cis-amide Hsp90 inhibitors. Org. Lett., 2009, 11(11), 2353-2356.
[http://dx.doi.org/10.1021/ol900783m] [PMID: 19435295]
[105]
Immormino, R.M.; Metzger, L.E., IV; Reardon, P.N.; Dollins, D.E.; Blagg, B.S.; Gewirth, D.T. Different poses for ligand and chaperone in inhibitor-bound Hsp90 and GRP94: Implications for paralog-specific drug design. J. Mol. Biol., 2009, 388(5), 1033-1042.
[http://dx.doi.org/10.1016/j.jmb.2009.03.071] [PMID: 19361515]
[106]
Duerfeldt, A.S.; Peterson, L.B.; Maynard, J.C.; Ng, C.L.; Eletto, D.; Ostrovsky, O.; Shinogle, H.E.; Moore, D.S.; Argon, Y.; Nicchitta, C.V.; Blagg, B.S. Development of a Grp94 inhibitor. J. Am. Chem. Soc., 2012, 134(23), 9796-9804.
[http://dx.doi.org/10.1021/ja303477g] [PMID: 22642269]
[107]
Yang, Y.; Liu, B.; Dai, J.; Srivastava, P.K.; Zammit, D.J.; Lefrançois, L.; Li, Z. Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. Immunity, 2007, 26(2), 215-226.
[http://dx.doi.org/10.1016/j.immuni.2006.12.005] [PMID: 17275357]
[108]
Crowley, V.M.; Khandelwal, A.; Mishra, S.; Stothert, A.R.; Huard, D.J.; Zhao, J.; Muth, A.; Duerfeldt, A.S.; Kizziah, J.L.; Lieberman, R.L.; Dickey, C.A.; Blagg, B.S. Development of glucose regulated protein 94-selective inhibitors based on the BnIm and radamide scaffold. J. Med. Chem., 2016, 59(7), 3471-3488.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00085] [PMID: 27003516]
[109]
Stothert, A.R.; Suntharalingam, A.; Tang, X.; Crowley, V.M.; Mishra, S.J.; Webster, J.M.; Nordhues, B.A.; Huard, D.J.E.; Passaglia, C.L.; Lieberman, R.L.; Blagg, B.S.J.; Blair, L.J.; Koren, J., III; Dickey, C.A. Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma. Sci. Rep., 2017, 7(1), 17951.
[http://dx.doi.org/10.1038/s41598-017-18344-4] [PMID: 29263415]
[110]
Stothert, A.R.; Suntharalingam, A.; Huard, D.J.; Fontaine, S.N.; Crowley, V.M.; Mishra, S.; Blagg, B.S.; Lieberman, R.L.; Dickey, C.A. Exploiting the interaction between Grp94 and aggregated myocilin to treat glaucoma. Hum. Mol. Genet., 2014, 23(24), 6470-6480.
[http://dx.doi.org/10.1093/hmg/ddu367] [PMID: 25027323]
[111]
Crowley, V.M.; Huard, D.J.E.; Lieberman, R.L.; Blagg, B.S.J. Second generation Grp94-selective inhibitors provide opportunities for the inhibition of metastatic cancer. Chemistry, 2017, 23(62), 15775-15782.
[http://dx.doi.org/10.1002/chem.201703398] [PMID: 28857290]
[112]
Khandelwal, A.; Crowley, V.M.; Blagg, B.S.J. Resorcinol-based Grp94-selective inhibitors. ACS Med. Chem. Lett., 2017, 8(10), 1013-1018.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00193] [PMID: 29057043]
[113]
Patel, P.D.; Yan, P.; Seidler, P.M.; Patel, H.J.; Sun, W.; Yang, C.; Que, N.S.; Taldone, T.; Finotti, P.; Stephani, R.A.; Gewirth, D.T.; Chiosis, G. Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nat. Chem. Biol., 2013, 9(11), 677-684.
[http://dx.doi.org/10.1038/nchembio.1335] [PMID: 23995768]
[114]
Jiang, F.; Guo, A.P.; Xu, J.C.; You, Q.D.; Xu, X.L. Discovery of a potent Grp94 selective inhibitor with anti-inflammatory efficacy in a mouse model of ulcerative colitis. J. Med. Chem., 2018, 61(21), 9513-9533.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00800] [PMID: 30351001]
[115]
Ernst, J.T.; Liu, M.; Zuccola, H.; Neubert, T.; Beaumont, K.; Turnbull, A.; Kallel, A.; Vought, B.; Stamos, D. Correlation between chemotype-dependent binding conformations of HSP90α/β and isoform selectivity-implications for the structure-based design of HSP90α/β selective inhibitors for treating neurodegenerative diseases. Bioorg. Med. Chem. Lett., 2014, 24(1), 204-208.
[http://dx.doi.org/10.1016/j.bmcl.2013.11.036] [PMID: 24332488]
[116]
Putcha, P.; Danzer, K.M.; Kranich, L.R.; Scott, A.; Silinski, M.; Mabbett, S.; Hicks, C.D.; Veal, J.M.; Steed, P.M.; Hyman, B.T.; McLean, P.J. Brain-permeable small-molecule inhibitors of Hsp90 prevent alpha-synuclein oligomer formation and rescue alpha-synuclein-induced toxicity. J. Pharmacol. Exp. Ther., 2010, 332(3), 849-857.
[http://dx.doi.org/10.1124/jpet.109.158436] [PMID: 19934398]
[117]
Ernst, J.T.; Neubert, T.; Liu, M.; Sperry, S.; Zuccola, H.; Turnbull, A.; Fleck, B.; Kargo, W.; Woody, L.; Chiang, P.; Tran, D.; Chen, W.; Snyder, P.; Alcacio, T.; Nezami, A.; Reynolds, J.; Alvi, K.; Goulet, L.; Stamos, D. Identification of novel HSP90α/β isoform selective inhibitors using structure-based drug design. demonstration of potential utility in treating CNS disorders such as Huntington’s disease. J. Med. Chem., 2014, 57(8), 3382-3400.
[http://dx.doi.org/10.1021/jm500042s] [PMID: 24673104]
[118]
Khandelwal, A.; Kent, C.N.; Balch, M.; Peng, S.; Mishra, S.J.; Deng, J.; Day, V.W.; Liu, W.; Subramanian, C.; Cohen, M.; Holzbeierlein, J.M.; Matts, R.; Blagg, B.S.J. Structure-guided design of an Hsp90β N-terminal isoform-selective inhibitor. Nat. Commun., 2018, 9(1), 425.
[http://dx.doi.org/10.1038/s41467-017-02013-1] [PMID: 29382832]
[119]
Plescia, J.; Salz, W.; Xia, F.; Pennati, M.; Zaffaroni, N.; Daidone, M.G.; Meli, M.; Dohi, T.; Fortugno, P.; Nefedova, Y.; Gabrilovich, D.I.; Colombo, G.; Altieri, D.C. Rational design of shepherdin, a novel anticancer agent. Cancer Cell, 2005, 7(5), 457-468.
[http://dx.doi.org/10.1016/j.ccr.2005.03.035] [PMID: 15894266]
[120]
Altieri, D.C.; Stein, G.S.; Lian, J.B.; Languino, L.R. TRAP-1, the mitochondrial Hsp90. Biochim. Biophys. Acta, 2012, 1823(3), 767-773.
[http://dx.doi.org/10.1016/j.bbamcr.2011.08.007] [PMID: 21878357]
[121]
Siegelin, M.D. Inhibition of the mitochondrial Hsp90 chaperone network: A novel, efficient treatment strategy for cancer? Cancer Lett., 2013, 333(2), 133-146.
[http://dx.doi.org/10.1016/j.canlet.2013.01.045] [PMID: 23376257]
[122]
Seo, Y.H. Organelle-specific Hsp90 inhibitors. Arch. Pharm. Res., 2015, 38(9), 1582-1590.
[http://dx.doi.org/10.1007/s12272-015-0636-1] [PMID: 26195286]
[123]
Lee, C.; Park, H.K.; Jeong, H.; Lim, J.; Lee, A.J.; Cheon, K.Y.; Kim, C.S.; Thomas, A.P.; Bae, B.; Kim, N.D.; Kim, S.H.; Suh, P.G.; Ryu, J.H.; Kang, B.H. Development of a mitochondria-targeted Hsp90 inhibitor based on the crystal structures of human TRAP1. J. Am. Chem. Soc., 2015, 137(13), 4358-4367.
[http://dx.doi.org/10.1021/ja511893n] [PMID: 25785725]
[124]
Park, H.K.; Jeong, H.; Ko, E.; Lee, G.; Lee, J.E.; Lee, S.K.; Lee, A.J.; Im, J.Y.; Hu, S.; Kim, S.H.; Lee, J.H.; Lee, C.; Kang, S.; Kang, B.H. Paralog specificity determines subcellular distribution, action mechanism, and anticancer activity of TRAP1 inhibitors. J. Med. Chem., 2017, 60(17), 7569-7578.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00978] [PMID: 28816449]

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