Synthesis and biological evaluation of a new class of geldanamycin derivatives as potent inhibitors of Hsp90

Journal of Medicinal Chemistry

Volumn 47, Issue 15, 2004, Pages 3865-3873

  Le Brazidec, Jean Yves ^a,b   Kamal, Adeela ^a,b   Busch, David ^a,b   Thao, Lia ^a,b   Zhang, Lin ^a,b   Timony, Gregg ^a,b   Grecko, Roy ^a,b   Trent, Katy ^a,b   Lough, Rachel ^a,b   Salazar, Tim ^a,b   Khan, Samina ^a,b   Burrows, Francis ^a,b   Boehm, Marcus F ^a,b  

^a BIOGEN   (United States)

^b Department of Chemistry ^*

Author keywords

[No Author keywords available]

Indexed keywords

17 AMINO 17 DEMETHOXYGELDANAMYCIN; ADENOSINE TRIPHOSPHATASE; AMIDE; ANSAMYCIN DERIVATIVE; ANTINEOPLASTIC AGENT; CARBAMIC ACID DERIVATIVE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GELDANAMYCIN; GELDANAMYCIN AMIDE; GELDANAMYCIN CARBAMATE; HEAT SHOCK PROTEIN 90; ONCOPROTEIN; PROTEASOME; PROTEIN INHIBITOR; PROTEIN KINASE B; RAF PROTEIN; TRIFLUOROMETHANESULFONIC ACID; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL LYSATE; CELL STRAIN MCF 7; CONTROLLED STUDY; DERIVATIZATION; DRUG EFFICACY; DRUG SOLUBILITY; DRUG STABILITY; DRUG SYNTHESIS; ENZYME INHIBITION; EX VIVO STUDY; FEMALE; GLIOBLASTOMA; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IN VITRO STUDY; LUNG SMALL CELL CANCER; MOUSE; NONHUMAN; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT; UBIQUITINATION;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZOQUINONES; BINDING, COMPETITIVE; CELL LINE, TUMOR; CHEMISTRY, PHARMACEUTICAL; DRUG STABILITY; FEMALE; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LACTAMS, MACROCYCLIC; MICE; MICE, INBRED BALB C; PROTEIN CONFORMATION; QUINONES; RECEPTOR, ERBB-2; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 3142545683     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0306125     Document Type: Article

References (33)

1. Gadjos, C.; Jordan, V. Selective Estrogen Receptor Modulators as a New Therapeutic Drug Group: Concept to Reality in a Decade. Clin. Breast Cancer 2002, 2, 272-281.
2. Carswell, C. I.; Figgitt, D. P. Bicalutamide: In Early-Stage Prostate Cancer. Drugs 2002, 62, 2471-2481.
3. Zhang, H.; Richter, M.; Greene, M. I. Therapeutic Monoclonal Antibodies for the ErbB Family of Receptor Tyrosine Kinases. Cancer Biol. Ther. 2003, 2 (4), S122-S126.
4. Cohen, M. H.; Williams, G. A.; Sridhara, R.; Chen, G.; Pazdur, R. FDA Drug Approval Summary: Gefitinib (ZD1839) (Iressa) Tablets. Oncologist 2003, 8, 303-306.
5. Capdeville, R.; Buchdunger, E.; Zimmermann, J.; Matter, A. Glivec (STI571, imatinib), a Rationally Developed Targeted Anticancer Drug. Nat. Rev. Drug Discovery 2002, 7, 493-502.
6. Pearl, L. H.; Prodromou, C. Curr. Opin. Struct. Biol. 2000, 10, 46.
7. Maloney, A.; Workman, P. Hsp90 as a New Therapeutic Target for Cancer Therapy: The Story Unfolds. Expert Opin. Biol. Ther. 2002, 2, 3-24.
8. Blank, M.; Mandel, M.; Keisari, Y.; Muruelo, D.; Lavie, G. Enhanced Ubiquinylation of Heat Shock Protein 90 as a Potential Mechanism for Mitotic Cell Death in Cancer Cells Induced with Hypericin. Cancer Res. 2003, 63, 8241-8247.
9. Gorre, M. E.; Ellwood-Yen, K.; Chiosis, G.; Rosen, N.; Sawyers, C. L. BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90. Blood 2002, 100, 3041-3044.
10. Solit, D. B.; Scher, H. I.; Rosen, N. Hsp90 as a Therapeutic Target in Prostate Cancer. Semin. Oncol. 2003, 30, 709-716.
11. Beliakoff, J.; Bagatell, R.; Paine-Murrieta, G.; Taylor, C. W.; Lykkesfeldt, A. E.; Whitesell, L. Hormone-Refractory Breast Cancer Remains Sensitive to the Antitumor Activity of Heat Shock Protein 90 Inhibitors. Clin. Cancer Res. 2003, 9, 4961-4971.
12. Schneider, C.; Sepp-Lorenzino, L.; Nimmesgern, E.; Ouerfelli, O.; Danishefsky, S.; Rosen, N.; Hartl, F. U. Pharmacologic Shifting of a Balance between Protein Refolding and Degradation Mediated by Hsp90. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14536-14541.
13. Solit, D. B.; Zheng, F. F.; Drobnjak, M.; Münster, P. N.; Higgins, B.; Verbel, D.; Heller, G.; Tong, W.; Cordon-Cardo, C.; Agus, D. B.; Scher, H. I.; 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. 2002, 8, 986-993.
14. Solit, D. B.; Basso, A. D.; Olshen, A. B.; Scher, H. I.; Rosen, N. Inhibition of Heat Shock Protein 90 Function Down-Regulates Akt Kinase and Sensitizes Tumors to Taxol. Cancer Res. 2003, 63, 2139-2144.
15. Basso, A. D.; Solit, D. B.; Chiosis, G.; Giri, B.; Tsichlis, P.; Rosen, N. Akt Forms an Intracellular Complex with Heat Shock Protein 90 (Hsp90) and Cdc37 and Is Destabilized by Inhibitors of Hsp90 Function. J. Biol. Chem. 2002, 277, 39858-39866.
16. Minami, Y.; Kiyoi, H.; Yamamoto, Y.; Yamamoto, K.; Ueda, R.; Saito, H.; Naoe, T. Selective Apoptosis of Tandemly Duplicated FLT3-Transformed Leukemia Cells by Hsp90 Inhibitors. Leukemia 2002, 16, 1535-1540.
17. 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 Protein in Oncogenic Transformation. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8324-8328.
18. Roe, S. M.; Podromou, C.; O'Brien, R.; Ladbury, J. E.; Piper, P. W.; Pearl, L. H. Structural Basis for Inhibition of the Hsp90 Molecular Chaperone by the Antitumor Antibiotics Radicicol and Geldanamycin. J. Med. Chem. 1999, 42, 260-266.
19. Jez, J. M.; Chen, J. C.-H.; Rastelli, G.; Stroud, R. M.; Santi, D. V. Crystal Structure and Molecular Modeling of 17-DMAG in Complex with Human Hsp90. Chem. Biol. 2003, 10, 361-368.
20. (a) Egorin, M. J.; Lagattuta, T. F.; Hamburger, D. R.; Covey, J. M.; White, K. D.; Musser, S. M.; Eiseman, J. L. Cancer Chemother. Pharmacol. 2002, 49, 7-19.
21. (b) Egorin, M. J.; Rosen, D. M.; Wolff, J. H.; Callery, P. S.; Musser, S. M.; Eiseman, J. M. Metabolism of 17-(Allylamino)-17-demethoxygeldanamycin by Murine and Human Hepatic Preparations. Cancer Res. 1998, 58, 2385.
22. Pan, S.-S.; Gonzalez, H. Mitomycin Antibiotic Reductive Potential and Related Pharmacological Activities. Mol. Pharmacol. 1990, 37, 966-970.
23. Sasaki, K.; Inoue, Y. Geldanamycin Derivatives and Antitumor Drug. U.S. Patent 4,261,989, April 14, 1981.
24. Neel, D. A.; Jirousek, M. R.; McDonald, J. H., III. Synthesis of Bisindolylmaleimides Using a Palladium Catalyzed Cross-Coupling Reaction. Bioorg. Med. Chem. Lett. 1998, 8, 47-50.
25. Wassenberg, J. J.; Reed, R. C.; Nicchitta, C. V. Ligand Interactions in the Adenosine Nucleotide-Binding Domain of the Hsp90 Chaperone, GRP94. J. Biol. Chem. 2000, 275, 22806-22814.
26. The standard error for this assay is ±30%.
27. Bundgaard, H. The Double Prodrug Concept and Its Applications. Adv. Drug Delivery Rev. 1989, 3, 39-65.
28. Kamal, A.; Thao, L.; Sensintaffar, J.; Zhang, L.; Boehm, M. F.; Fritz, L. C.; Burrows, F. J. Nature 2003, 425, 407-410.
29. Jez, J. M.; Chen, J. C.; Rastelli, G.; Stroud, R. M.; Santi, D. V. Crystal Structure and Molecular Modeling of 17-DMAG in Complex with Human Hsp90. Chem. Biol. 2003, 10, 361-368.
30. (a) Stebbins, C. E.; Russo, A. A.; Schneider, C.; Rosen, N.; Hartl, F. U.; Pavletich, N. P. Crystal Structure of an Hsp90-Geldanamycin Complex: Targeting of a Protein Chaperone by an Antitumor Agent. Cell 1997, 89, 239-250.
31. (b) Roe, S. M.; Podromou, C.; O'Brien, R.; Ladbury, J. E.; Piper, P. W.; Pearl, L. H. Structural Basis for Inhibition of the Hsp90 Molecular Chaperone by the Antitumor Antibiotics Radicicol and Geldanamycin. J. Med. Chem. 1999, 42, 260-266.
32. Egorin, M. J.; Zuhowski, E. G.; Rosen, M. D.; Sentz, D. L.; Covey, J. M.; Eiseman, J. L. Plasma Pharmacokinetics of Tissue Distribution of 17-(Allylamino)-17-demethoxygeldanamycin (NSC 330507) in SD2F1 Mice. Cancer Chemother Pharmacol. 2001, 47, 291-302.
33. Corey, A.; Owen, T.; Barltrop, J.; Cory, J. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 1991, 3, 207-212.