Inhibitors of the HSP90 Molecular Chaperone: Current Status

Advances in Cancer Research

Volumn 95, Issue , 2006, Pages 323-348

  Sharp, Swee ^a   Workman, Paul ^a  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

17 ALLYLAMINO 17 DEMETHOXYGELDANAMYCIN; 17 AMINO 17 DEMETHOXYGELDANAMYCIN; 17 DIMETHYLAMINOETHYLAMINO 17 DEMETHOXYGELDANAMYCIN; ADENOSINE 5' (N ETHYLCARBOXAMIDE); ANTINEOPLASTIC AGENT; BETA ZEARALENOL; CCT 0129397; CCT 0181159; CCT 018159; CISPLATIN; CNF 1010; GELDANAMYCIN; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; HERBIMYCIN A; HISTONE DEACETYLASE INHIBITOR; KF 55823; KF 58333; KOS 953; MYCOGRAB; NOVOBIOCIN; OXIME DERIVATIVE; PACLITAXEL; PU24F CL; PURINE DERIVATIVE; PYRAZOLE DERIVATIVE; RADESTER; RADICICOL; RECOMBINANT ANTIBODY; SHEPHERDIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VER 490009; VER 49009; VORINOSTAT;

CANCER THERAPY; CANDIDIASIS; CLINICAL TRIAL; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG SOLUBILITY; DRUG STABILITY; DRUG TOLERABILITY; EYE TOXICITY; HUMAN; HYDROLYSIS; LIVER TOXICITY; MELANOMA; MONONUCLEAR CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; TUMOR BIOPSY;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZOQUINONES; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LACTAMS, MACROCYCLIC; MODELS, BIOLOGICAL; MODELS, CHEMICAL; MOLECULAR CHAPERONES; NEOPLASMS; NOVOBIOCIN; PURINES; PYRAZOLES;

EID: 33746191768     PISSN: 0065230X     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S0065-230X(06)95009-X     Document Type: Review

References (113)

1. Agatsuma T., Ogawa H., Akasaka K., Asai A., Yamashita Y., Mizukami T., Akinaga S., and Saitoh Y. Halohydrin and oxime derivatives of radicicol: Synthesis and antitumor activities. Bioorg. Med. Chem. 10 (2002) 3445-3454
2. Argon Y., and Simen B.B. GRP94, an ER chaperone with protein and peptide binding properties. Semin. Cell Dev. Biol. 10 (1999) 495-505
3. Banerji U., O'Donnell A., Scurr M., Pacey S., Stapleton S., Asad Y., Simmons L., Maloney A., Raynaud F., Campbell M., Walton M., Lakhani S., et al. Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J. Clin. Oncol. 23 (2005) 4152-4161
4. Bauer S., Yu L., Read M., Norman E., Demetri G., and Fletcher J. IPI504, a novel HSP90 inhibitor, causes inhibition and degradation of KIT in imatinib-resistant GIST: Rationale for therapeutic targeting in GIST. Clin. Cancer Res. 11 Suppl. 24 (2005) 9111s 9111s
5. Bertram J., Palfner K., Hiddemann W., and Kneba M. Increase of P-glycoprotein-mediated drug resistance by hsp 90 beta. Anticancer Drugs 7 (1996) 838-845
6. Biamonte M.A., Shi J., Hong K., Hurst D.C., Zhang L., Fan J., Busch D.J., Karjian P.L., Maldonado A.A., Sensintaffar J.L., Yang Y.C., Kamal A., et al. Orally active purine-based inhibitors of the heat shock protein 90. J. Med. Chem. 49 (2006) 817-828
7. Burger A.M., Fiebig H.H., Stinson S.F., and Sausville E.A. 17-(Allylamino)-17-demethoxygeldanamycin activity in human melanoma models. Anticancer Drugs 15 (2004) 377-387
8. Byrd C.A., Bornmann W., Erdjument-Bromage H., Tempst P., Pavletich N., Rosen N., Nathan C.F., and Ding A. Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide. Proc. Natl. Acad. Sci. USA 96 (1999) 5645-5650
9. Chen B., Piel W.H., Gui L., Bruford E., and Monteiro A. The HSP90 family of genes in the human genome: Insights into their divergence and evolution. Genomics 86 (2005) 627-637
10. 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., et al. 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. 15 (2005) 3338-3343
11. Chiosis G., Lucas B., Shtil A., Huezo H., and Rosen N. Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase. Bioorg. Med. Chem. 10 (2002) 3555-3564
12. Chiosis G., Huezo H., Rosen N., Mimnaugh E., Whitesell L., and Neckers L. 17AAG: Low target binding affinity and potent cell activity-finding an explanation. Mol. Cancer Ther. 2 (2003) 123-129
13. Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J. Biol. Chem. 269 (1994) 787-790
14. Connell P., Ballinger C.A., Jiang J., Wu Y., Thompson L.J., Hohfeld J., and Patterson C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 3 (2001) 93-96
15. da Rocha D.S., Friedlos F., Light Y., Springer C., Workman P., and Marais R. Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res. 65 (2005) 10686-10691
16. DeBoer C., Meulman P.A., Wnuk R.J., and Peterson D.H. Geldanamycin, a new antibiotic. J. Antibiot. (Tokyo) 23 (1970) 442-447
17. Dragovich T., Gordon M., Saif W., Erlichman C., Toft D., Timony G., Burrows F., Padgett C., DeJager R., and Von Hoff D. Phase I study of CNF1010 (lipid formulation of 17-(allylamino)-17-demethoxygeldnamycin: 17AAG). Clin. Cancer Res. 11 Suppl. 24 (2005) 9117s 9117s
18. Dymock B.W., Drysdale M.J., McDonald E., and Workman P. Inhibitors of HSP90 and other chaperones for the treatment of cancer. Expert. Opin. Ther. Patents 14 (2004) 837-847
19. Dymock B.W., Barril X., Brough P.A., Cansfield J.E., Massey A., McDonald E., Hubbard R.E., Surgenor A., Roughley S.D., Webb P., Workman P., Wright L., et al. Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design. J. Med. Chem. 48 (2005) 4212-4215
20. Egorin M.J., Zuhowski E.G., Rosen D.M., Sentz D.L., Covey J.M., and Eiseman J.L. Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1. Cancer Chemother. Pharmacol. 47 (2001) 291-302
21. Egorin M.J., Lagattuta T.F., Hamburger D.R., Covey J.M., White K.D., Musser S.M., and Eiseman J.L. Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats. Cancer Chemother. Pharmacol. 49 (2002) 7-19
22. Eiseman J.L., Lan J., Lagattuta T.F., Hamburger D.R., Joseph E., Covey J.M., and Egorin M.J. Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]geldanamycin (17DMAG, NSC 707545) in C. B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts. Cancer Chemother. Pharmacol. 55 (2005) 21-32
23. Eustace B.K., Sakurai T., Stewart J.K., Yimlamai D., Unger C., Zehetmeier C., Lain B., Torella C., Henning S.W., Beste G., Scroggins B.T., Neckers L., et al. Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat. Cell Biol. 6 (2004) 507-514
24. Felts S.J., Owen B.A., Nguyen P., Trepel J., Donner D.B., and Toft D.O. The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties. J. Biol. Chem. 275 (2000) 3305-3312
25. Fuino L., Bali P., Wittmann S., Donapaty S., Guo F., Yamaguchi H., Wang H.G., Atadja P., and Bhalla K. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol. Cancer Ther. 2 (2003) 971-984
26. Fukazawa H., Uehara Y., Murakami Y., Mizuno S., Hamada M., and Takeuchi T. Labeling of v-Src and BCR-ABL tyrosine kinases with [14C]herbimycin A and its use in the elucidation of the kinase inactivation mechanism. FEBS Lett. 340 (1994) 155-158
27. George P., Bali P., Annavarapu S., Scuto A., Fiskus W., Guo F., Sigua C., Sondarva G., Moscinski L., Atadja P., and Bhalla K. Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 105 (2005) 1768-1776
28. Goetz M.P., Toft D., Reid J., Ames M., Stensgard B., Safgren S., Adjei A.A., Sloan J., Atherton P., Vasile V., Salazaar S., Adjei A., et al. Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. J. Clin. Oncol. 23 (2005) 1078-1087
29. Gonzalez V.M., Fuertes M.A., Alonso C., and Perez J.M. Is cisplatin-induced cell death always produced by apoptosis?. Mol. Pharmacol. 59 (2001) 657-663
30. Gore L., Holden S., Basche M., Raj S., Arnold I., O'Bryant C., Witta S., Rohde B., McCoy C., and Eckhart S. Updated results from a phase I trial of the histone deacetylase (HDAC) inhibitor MS-275 in patients with refractory solid tumours. Proc. Am. Assoc. Clin. Oncol. 22 (2004) 3026 3026
31. Grammatikakis N., Vultur A., Ramana C.V., Siganou A., Schweinfest C.W., Watson D.K., and Raptis L. The role of Hsp90N, a new member of the Hsp90 family, in signal transduction and neoplastic transformation. J. Biol. Chem. 277 (2002) 8312-8320
32. Grbovic O.M., Basso A.D., Sawai A., Ye Q., Friedlander P., Solit D., and Rosen N. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc. Natl. Acad. Sci. USA 103 (2006) 57-62
33. Gress T.M., Muller-Pillasch F., Weber C., Lerch M.M., Friess H., Buchler M., Beger H.G., and Adler G. Differential expression of heat shock proteins in pancreatic carcinoma. Cancer Res. 54 (1994) 547-551
34. Guo W., Reigan P., Siegel D., Zirrolli J., Gustafson D., and Ross D. Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:quinone oxidoreductase 1: Role of 17-AAG hydroquinone in heat shock protein 90 inhibition. Cancer Res. 65 (2005) 10006-10015
35. Hanahan D., and Weinberg R.A. The hallmarks of cancer. Cell 100 (2000) 57-70
36. Hargreaves R., David C.L., Whitesell L., and Skibo E.B. Design of quinolinedione-based geldanamycin analogues. Bioorg. Med. Chem. Lett. 13 (2003) 3075-3078
37. He H., Zatorska D., Kim J., Aguirre J., Llauger L., She Y., Wu N., Immormino R.M., Gewirth D.T., and Chiosis G. Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. J. Med. Chem. 49 (2006) 381-390
38. Hernandez M.P., Sullivan W.P., and Toft D.O. The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex. J. Biol. Chem. 277 (2002) 38294-38304
39. Hickey E., Brandon S.E., Smale G., Lloyd D., and Weber L.A. Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol. Cell. Biol. 9 (1989) 2615-2626
40. Hostein I., Robertson D., DiStefano F., Workman P., and Clarke P.A. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res. 61 (2001) 4003-4009
41. Isaacs J.S., Xu W., and Neckers L. Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell 3 (2003) 213-217
42. Itoh H., Ogura M., Komatsuda A., Wakui H., Miura A.B., and Tashima Y. A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90. Biochem. J. 343 Pt. 3 (1999) 697-703
43. Ivy P.S., and Schoenfeldt M. Clinical trials referral resource. Current clinical trials of 17-AG and 17-DMAG. Oncology (Williston. Park) 18 (2004) 610-620
44. Jameel A., Skilton R.A., Campbell T.A., Chander S.K., Coombes R.C., and Luqmani Y.A. Clinical and biological significance of HSP89 alpha in human breast cancer. Int. J. Cancer 50 (1992) 409-415
45. Janin Y.L. Heat shock protein 90 inhibitors. A text book example of medicinal chemistry?. J. Med. Chem. 48 (2005) 7503-7512
46. Kamal A., Thao L., Sensintaffar J., Zhang L., Boehm M.F., Fritz L.C., and Burrows F.J. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425 (2003) 407-410
47. Kartalou M., and Essigmann J.M. Mechanisms of resistance to cisplatin. Mutat. Res. 478 (2001) 23-43
48. Kartalou M., and Essigmann J.M. Recognition of cisplatin adducts by cellular proteins. Mutat. Res. 478 (2001) 1-21
49. Kaur G., Belotti D., Burger A.M., Fisher-Nielson K., Borsotti P., Riccardi E., Thillainathan J., Hollingshead M., Sausville E.A., and Giavazzi R. Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: An orally bioavailable heat shock protein 90 modulator. Clin. Cancer Res. 10 (2004) 4813-4821
50. Kelland L.R., Sharp S.Y., Rogers P.M., Myers T.G., and Workman P. DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J. Natl. Cancer Inst. 91 (1999) 1940-1949
51. Kristeleit R., Tandy D., Atadja P., Patnaik A., DeBono J., Judson I., Kaye S., Workman P., and Aherne W. Effects of the histone deacetylase inhibitor (HDACi) LAQ824 on histone acetylation, Hsp70 and c-Raf in peripheral blood lymphocytes from patients with advanced solid tumours enrolled in a phase I clinical trial. Proc. Am. Assoc. Clin. Oncol. 22 (2004) 3032 3032
52. Kurebayashi J., Otsuki T., Kurosumi M., Soga S., Akinaga S., and Sonoo H. A radicicol derivative, KF58333, inhibits expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor, angiogenesis and growth of human breast cancer xenografts. Jpn. J Cancer Res. 92 (2001) 1342-1351
53. Kwon H.J., Yoshida M., Fukui Y., Horinouchi S., and Beppu T. Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol. Cancer Res. 52 (1992) 6926-6930
54. Langer T., Schlatter H., and Fasold H. Evidence that the novobiocin-sensitive ATP-binding site of the heat shock protein 90 (hsp90) is necessary for its autophosphorylation. Cell Biol. Int. 26 (2002) 653-657
55. Le Brazidec J.Y., Kamal A., Busch D., Thao L., Zhang L., Timony G., Grecko R., Trent K., Lough R., Salazar T., Khan S., Burrows F., et al. Synthesis and biological evaluation of a new class of geldanamycin derivatives as potent inhibitors of Hsp90. J. Med. Chem. 47 (2004) 3865-3873
56. Loehrer P.J., and Einhorn L.H. Drugs five years later. Cisplatin. Ann. Intern. Med. 100 (1984) 704-713
57. Maloney A., and Workman P. HSP90 as a new therapeutic target for cancer therapy: The story unfolds. Expert Opin. Biol. Ther. 2 (2002) 3-24
58. Marcu M.G., Chadli A., Bouhouche I., Catelli M., and 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. 275 (2000) 37181-37186
59. Marcu M.G., Schulte T.W., and Neckers L. Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. J. Natl. Cancer Inst. 92 (2000) 242-248
60. Matthews R.C., and Burnie J.P. Recombinant antibodies: A natural partner in combinatorial antifungal therapy. Vaccine 22 (2004) 865-871
61. Matthews R.C., Rigg G., Hodgetts S., Carter T., Chapman C., Gregory C., Illidge C., and Burnie J. Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob. Agents Chemother. 47 (2003) 2208-2216
62. Moulin E., Zoete V., Barluenga S., Karplus M., and Winssinger N. Design, synthesis, and biological evaluation of HSP90 inhibitors based on conformational analysis of radicicol and its analogues. J. Am. Chem. Soc. 127 (2005) 6999-7004
63. Munster P.N., Basso A., Solit D., Norton L., and Rosen N. Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. See: (2001)
64. Sausville E.A. Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: Sequence and tumor biology matters. Clin. Cancer Res. 7 (2001) 2155-2158
65. Munster P.N., Marchion D.C., Basso A.D., and Rosen N. Degradation of HER2 by ansamycins induces growth arrest and apoptosis in cells with HER2 overexpression via a HER3, phosphatidylinositol 3′-kinase-AKT-dependent pathway. Cancer Res. 62 (2002) 3132-3137
66. Obermann W.M., Sondermann H., Russo A.A., Pavletich N.P., and Hartl F.U. In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J. Cell Biol. 143 (1998) 901-910
67. Pacey S., Banerji U., Judson I., and Workman P. Hsp90 inhibitors in the clinic. "Handbook of Experimental Pharmacology. Molecular Chaperones in Health and Disease," Vol. 172 (2006), Berlin Heidelberg Springer-Verlag, Germany 331-358
68. Panaretou B., Siligardi G., Meyer P., Maloney A., Sullivan J.K., Singh S., Millson S.H., Clarke P.A., Naaby-Hansen S., Stein R., Cramer R., Mollapour M., et al. Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol. Cell 10 (2002) 1307-1318
69. Pearl L.H., and Prodromou C. Structure, function, and mechanism of the Hsp90 molecular chaperone. Adv. Protein Chem. 59 (2001) 157-186
70. Persons D.L., Yazlovitskaya E.M., Cui W., and Pelling J.C. Cisplatin-induced activation of mitogen-activated protein kinases in ovarian carcinoma cells: Inhibition of extracellular signal-regulated kinase activity increases sensitivity to cisplatin. Clin. Cancer Res. 5 (1999) 1007-1014
71. 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., et al. Rational design of shepherdin, a novel anticancer agent. Cancer Cell 7 (2005) 457-468
72. Prodromou C., Roe S.M., O'Brien R., Ladbury J.E., Piper P.W., and Pearl L.H. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90 (1997) 65-75
73. Richter K., and Buchner J. Hsp90: Chaperoning signal transduction. J. Cell Physiol. 188 (2001) 281-290
74. Roe S.M., Prodromou C., O'Brien R., Ladbury J.E., Piper P.W., and Pearl L.H. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J. Med. Chem. 42 (1999) 260-266
75. Roe S.M., Ali M.M., Meyer P., Vaughan C.K., Panaretou B., Piper P.W., Prodromou C., and Pearl L.H. The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37). Cell 116 (2004) 87-98
76. Rosenhagen M.C., Soti C., Schmidt U., Wochnik G.M., Hartl F.U., Holsboer F., Young J.C., and Rein T. The heat shock protein 90-targeting drug cisplatin selectively inhibits steroid receptor activation. Mol. Endocrinol. 17 (2003) 1991-2001
77. Rowlands M.G., Newbatt Y.M., Prodromou C., Pearl L.H., Workman P., and Aherne W. High-throughput screening assay for inhibitors of heat-shock protein 90 ATPase activity. Anal. Biochem. 327 (2004) 176-183
78. Sain N., Krishan B., Ormerod M.G., De Rienzo A., Liu W., Kaye S.B., Workman P., and Jackman A. Potentiation of paclitaxel activity in human ovarian carcinoma cell lines with high levels of activity AKT. Mol. Cancer Ther. (2006) (in press)
79. Sanderson S., Valenti M., Gowan S., Patterson L., Ahmad Z., Workman P., and Eccles S.A. Benzoquinone ansamycin heat shock protein 90 inhibitors modulate multiple functions required for tumor angiogenesis. Mol. Cancer Ther. 5 (2006) 522-532
80. Schiff P.B., and Horwitz S.B. Taxol stabilizes microtubules in mouse fibroblast cells. Proc. Natl. Acad. Sci. USA 77 (1980) 1561-1565
81. Schnur R.C., Corman M.L., Gallaschun R.J., Cooper B.A., Dee M.F., Doty J.L., Muzzi M.L., DiOrio C.I., Barbacci E.G., Miller P.E., et al. erbB-2 oncogene inhibition by geldanamycin derivatives: Synthesis, mechanism of action, and structure-activity relationships. J. Med. Chem. 38 (1995) 3813-3820
82. Schnur R.C., Corman M.L., Gallaschun R.J., Cooper B.A., Dee M.F., Doty J.L., Muzzi M.L., Moyer J.D., DiOrio C.I., and Barbacci E.G. Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives. J. Med. Chem. 38 (1995) 3806-3812
83. Scholz G.M., Cartledge K., and Hall N.E. Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37. J. Biol. Chem. 276 (2001) 30971-30979
84. Schulte T.W., and Neckers L.M. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. 42 (1998) 273-279
85. Sharp S., Boxall K., Titley J., Drysdale M., and Workman P. Mechanisms of action of the novel HSP90 inhibitor, CCT018159 in malignant melanoma cell lines. Clin. Cancer Res. 9 Suppl. 17 (2003) 73
86. Shen G., and Blagg B.S. Radester, a novel inhibitor of the Hsp90 protein folding machinery. Org. Lett. 7 (2005) 2157-2160
87. Shen G., Yu X.M., and Blagg B.S. Syntheses of photolabile novobiocin analogues. Bioorg. Med. Chem. Lett. 14 (2004) 5903-5906
88. Shiotsu Y., Soga S., and Akinaga S. Heat shock protein 90-antagonist destabilizes Bcr-Abl/HSP90 chaperone complex. Leuk. Lymphoma 43 (2002) 961-968
89. Smith V., Sausville E.A., Camalier R.F., Fiebig H.H., and Burger A.M. Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: Effects on Hsp90 and client proteins in melanoma models. Cancer Chemother. Pharmacol. 56 (2005) 126-137
90. Soga S., Sharma S.V., Shiotsu Y., Shimizu M., Tahara H., Yamaguchi K., Ikuina Y., Murakata C., Tamaoki T., Kurebayashi J., Schulte T.W., Neckers L.M., et al. Stereospecific antitumor activity of radicicol oxime derivatives. Cancer Chemother. Pharmacol. 48 (2001) 435-445
91. Soga S., Shiotsu Y., Akinaga S., and Sharma S.V. Development of radicicol analogues. Curr. Cancer Drug Targets 3 (2003) 359-369
92. Soldano K.L., Jivan A., Nicchitta C.V., and Gewirth D.T. Stucture of the N-terminal domain of GRP94: Basis for ligand specificity and regulation. J. Biol. Chem. 48 (2003) 48330-48338
93. Solit D.B., Zheng F.F., Drobnjak M., Munster P.N., Higgins B., Verbel D., Heller G., Tong W., Cordon-Cardo C., Agus D.B., Scher H.I., and Rosen N. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin. Cancer Res. 8 (2002) 986-993
94. Soti C., Racz A., and 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. 277 (2002) 7066-7075
95. Sreedhar A.S., Kalmar E., Csermely P., and Shen Y.F. Hsp90 isoforms: Functions, expression and clinical importance. FEBS Lett. 562 (2004) 11-15
96. Supko J.G., Hickman R.L., Grever M.R., and Malspeis L. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol. 36 (1995) 305-315
97. Tsutsumi S., Scroggins B., Tian Z., Santi D., and Neckers L. Cell-impermeable derivatives of the heat shock protein 90 inhibitor geldanamycin display low cytotoxicity but strongly inhibit tumor cell invasion in vitro. Clin. Cancer Res. 11 Suppl. 24 (2005) 9149s 9149s
98. Vilenchik M., Solit D., Basso A., Huezo H., Lucas B., He H., Rosen N., Spampinato C., Modrich P., and Chiosis G. Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90. Chem. Biol. 11 (2004) 787-797
99. Wani M.C., Taylor H.L., Wall M.E., Coggon P., and McPhail A.T. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 93 (1971) 2325-2327
100. Wegele H., Muschler P., Bunck M., Reinstein J., and Buchner J. Dissection of the contribution of individual domains to the ATPase mechanism of Hsp90. J. Biol. Chem. 278 (2003) 39303-39310
101. Whitesell L., Mimnaugh E.G., De Costa B., Myers C.E., and 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 91 (1994) 8324-8328
102. Wong E., and Giandomenico C.M. Current status of platinum-based antitumor drugs. Chem. Rev. 99 (1999) 2451-2466
103. Workman P. Auditing the pharmacological accounts for Hsp90 molecular chaperone inhibitors: Unfolding the relationship between pharmacokinetics and pharmacodynamics. Mol. Cancer Ther. 2 (2003) 131-138
104. Wright L., Barril X., Dymock B., Sheridan L., Surgenor A., Beswick M., Drysdale M., Collier A., Massey A., Davies N., Fink A., Fromont C., et al. Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms. Chem. Biol. 11 (2004) 775-785
105. Yamada S., Ono T., Mizuno A., and Nemoto T.K. A hydrophobic segment within the C-terminal domain is essential for both client-binding and dimer formation of the HSP90-family molecular chaperone. Eur. J. Biochem. 270 (2003) 146-154
106. Yamamoto K., Garbaccio R.M., Stachel S.J., Solit D.B., Chiosis G., Rosen N., and Danishefsky S.J. Total synthesis as a resource in the discovery of potentially valuable antitumor agents: Cycloproparadicicol. Angew. Chem. Int. Ed. Engl. 42 (2003) 1280-1284
107. Yang Z.Q., Geng X., Solit D., Pratilas C.A., Rosen N., and Danishefsky S.J. New efficient synthesis of resorcinylic macrolides via ynolides: Establishment of cycloproparadicicol as synthetically feasible preclinical anticancer agent based on Hsp90 as the target. J. Am. Chem. Soc. 126 (2004) 7881-7889
108. Yin X., Zhang H., Burrows F., Zhang L., and Shores C.G. Potent activity of a novel dimeric heat shock protein 90 inhibitor against head and neck squamous cell carcinoma in vitro and in vivo. Clin. Cancer Res. 11 (2005) 3889-3896
109. Yu X., Guo Z.S., Marcu M.G., Neckers L., Nguyen D.M., Chen G.A., and Schrump D.S. Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. J. Natl. Cancer Inst. 94 (2002) 504-513
110. Yu X.M., Shen G., Neckers L., Blake H., Holzbeierlein J., Cronk B., and Blagg B.S. Hsp90 inhibitors identified from a library of novobiocin analogues. J. Am. Chem. Soc. 127 (2005) 12778-12779
111. Yufu Y., Nishimura J., and Nawata H. High constitutive expression of heat shock protein 90 alpha in human acute leukemia cells. Leuk. Res. 16 (1992) 597-605
112. Yun B.G., Huang W., Leach N., Hartson S.D., and Matts R.L. Novobiocin induces a distinct conformation of Hsp90 and alters Hsp90-cochaperone-client interactions. Biochemistry 43 (2004) 8217-8229
113. Zhao J.F., Nakano H., and Sharma S. Suppression of RAS and MOS transformation by radicicol. Oncogene 11 (1995) 161-173