Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N-terminal ATP binding site

Current Topics in Medicinal Chemistry

Volumn 6, Issue 11, 2006, Pages 1173-1182

  Hadden, M Kyle ^a   Lubbers, Donna J ^a   Blagg, Brian S J ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

17 AAG; Cancer; Chimera; Geldanamycin; Hsp90; Radanamycin; Radicicol

Indexed keywords

17 ALLYLAMINO 17 DEMETHOXYGELDANAMYCIN; 17 AMINOPROPYLAMINOGELDANAMYCIN; 17 DIMETHYLAMINOETHYLAMINO 17 DEMETHOXYGELDANAMYCIN; 2 MORPHOLINO 8 PHENYLCHROMONE; ADENOSINE TRIPHOSPHATE; AIGIALOMYCIN D; ANSAMYCIN DERIVATIVE; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; CHAPERONE; CYCLOPROPARADICICOL; GELDANAMYCIN; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; KF 23542; KF 25706; KF 58333; KOSN 1558; KOSN 1559; KOSN 1630; KOSN 1631; KOSN 1859; KOSN 1877; NATURAL PRODUCT; POCHONIN A; POCHONIN D; PROTEIN TYROSINE KINASE; RADICICOL; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO TERMINAL SEQUENCE; ANTINEOPLASTIC ACTIVITY; BINDING SITE; BIOLOGICAL ACTIVITY; BREAST CANCER; CANCER CELL CULTURE; CANCER THERAPY; CLINICAL TRIAL; DRUG SELECTIVITY; DRUG TARGETING; HUMAN; IC 50; IN VITRO STUDY; LIVER TOXICITY; NONHUMAN; PROSTATE CANCER; REVIEW; TUMOR GROWTH;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; BENZOQUINONES; BINDING SITES; DRUG DESIGN; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LACTAMS, MACROCYCLIC; MACROLIDES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NEOPLASMS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33746381708     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802606777812031     Document Type: Review

References (57)

1. DeBoer, C.; Meulman, P.A.; Wnuk, R.J.; Peterson, D.H. Geldamycin, a new Antibiotic. J. Antibiot. 1970, 23, 442-447.
2. Jove, R.; Hanafusa, H. Cell Transformation by the Viral src Oncogene. Annu. Rev. Cell. Bio. 1987, 3, 31-56.
3. Uehara, Y.; Murakami, Y.; Mizuno, S.; Kawai, S. Inhibition of Transforming Activity of Tyrosine Kinase Oncogenes by Herbimycin A. Virology 1988, 164, 294-298.
4. Whitesell, L.; Shiffin, S.D.; Schwab, G.; Neckers, L.M. Benzoquinonoid Ansamycins Possess Selective Tumoricidal Activity Unrelated to src Kinase Inhibition. Cancer Res. 1992, 52, 1721-1728.
5. 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, 8324-8328.
6. Eleuteri, A.M.; Cuccioloni, M.; Bellesi, J.; Lupidi, G.; Fioretti, E.; Angeletti, M. Interaction of Hsp90 with 20S Proteasome: Thermodynamic and Kinetic Characterization. Proteins: Struc. Funct. Genet. 2002, 48, 169-177.
7. 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.
8. 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, 65-75.
9. Schnur, R.C.; Corman, M.L. Tandem [3,3]-Sigmatropic Rearrangements in an Ansamycin-Stereospecific Conversion of an (S)-Allylic Alcohol to an (S)-AllylicAmine Derivative. J. Org. Chem. 1994, 59, 2581-2584.
10. Rinehart, K.L.; Shield, L.S. Chemistry of the Ansamycin Antibiotics. Fortschr. Chem. Org. Naturst. 1976, 33, 231-307.
11. Roe, M.S.; Prodromou, 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.
12. Dikalov, S.; Landmesser, U.; Harrison, D.G. Geldanamycin Leads to Superoxide Formation by Enzymatic and Non-enzymatic Cycling. J. Biol. Chem. 2002, 277, 25480-25485.
13. Supko, J.G.; Hickman, R.L.; Grever, M.R.; Malspeis, L. Preclinical Pharmacologic Evaluation of Geldanamycin as an Antitumor Agent. Cancer. Chemother. Pharmacol. 1995, 36, 305-315.
14. erb-2 In Vitro and In Vivo by Geldanamycin and Dihydrogeldanamycin Derivatives. J. Med. Chem. 1995, 38, 3806-3812.
15. Schulte, T.W.; Neckers, L.M. The Benzoquinone Ansamycin 17-allylamino-17-demethoxygeldanamycin Binds to Hsp9O and Shares Important Biological Activities with Geldanamycin. Cancer Chemother. Pharmacol. 1998, 42, 273-279.
16. Banerji, U. Preclinical and Clinical Activity of the Molecular Chaperone Inhibitor 17-Allylamino, 17-Demethoxygeldanamycin in Malignant Melanoma. Proc. Am. Assoc. Cancer. Res. 2003, 44, 677.
17. Sausville, E.A. Clinical Development of 17-Allylamino, 17-Demethoxygeldanamycin. Curr. Cancer Drug Targets 2003, 3, 377-383.
18. Tian, Z-Q.; Liu, Y.; Zhang, D.; Wang, Z.; Dong, S.D.; Carreras, C.W.; Zhou, Y.; Rastelli, G.; Santi, D.V.; Myles, D.C. Synthesis and Biological Activities of Novel 17-Aminogeldanamycin Derivatives. Bioorg. Med. Chem. 2004, 12, 5317-5329.
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. Zheng, F.F.; Kuduk, S.D.; Chiosis, G.; Munster, P.N.; Sepp-Lorenzino, L.; Danishefsky, S.J.; Rosen, N. Identification of a Geldanamycin Dimer that Induces the Selective Degradation of HER-family Tyrosine Kinases. Cancer Res. 2000, 60, 2090-2094.
21. Kuduk, S.D.; Zheng, F.F.; Sepp-Lorenzino, L.; Rosen, N.; Danishefsky, S.J. Synthesis and Evaluation of Geldanamycin-Estradiol Hybrids. Bioorg. Med. Chem. Lett. 1999, 9, 1233-1238.
22. Kuduk, S.D.; Harris, C.R.; Zheng, F.F.; Sepp-Lorenzino, L.; Ouerfelli, Q.; Rosen, N.; Danishefsky, S.J. Synthesis and Evaluation of Geldanamycin-Testosterone Hybrids. Bioorg. Med. Chem. Lett. 2000, 10, 1303-1306.
23. Chiosis, G.; Rosen, N.; Sepp-Lorenzino, L. LY294002-Geldanamycin Heterodimers as Selective Inhibitors of the P13K and P13K-related family. Bioorg. Med. Chem. Lett. 2001, 11, 909-913.
24. Baselga, J. Clinical Trials of Herceptin (trastuzumab). Eur. J. Cancer 2001, 37 (Suppl.1), S18-S24.
25. Mandler, R.; Wu, C.; Sausvilte, E.A.; Roettinger, A.J.; Newman, D.J.; Ho, D.K.; King, C.R.; Yang, D.; Lippman, M.E.; Landolfi, N.F.; Dadachova, E.; Brechbiel, M.W.; Waldmann, T.A. Immunoconjugates of Geldanamycin and Anti-Her2 Monoclonal Antibodies: Antiproliferative Activity on Human Breast Carcinoma Cell Lines. J. Natl. Cancer Inst. 2000, 92, 1573-1581.
26. Mandler, R.; Kobayashi, H.; Hinson, E.R.; Brechbiel. M.W.; Waldiriann, T.A. Herceptin-Geldanamycin Immunoconjugates: Pharmacokinetics, Biodistribution, and Enhanced Antitumor Activity. Cancer Res. 2004, 64, 1460-1467.
27. Andrus, M.B.; Meredith, E.L.; Hicken, E.J.; Simmons, B.L.; Glancey, R.R.; Ma, W. Total Synthesis of (+)-Geldanamycin and (-)-o-Guinogeldanamycin: Asymmetric Glycolate Aldol Reactions and Biological Evaluation. J. Org. Chem. 2003, 68, 8162-8169.
28. Patel, K.; Piagentini, M.; Rascher, A.; Tian, Z-Q.; Buchanan, G.O.; Regentin, R.; Hu, Z.; Hutchinson, C.R.; McDaniel, R. Engineered Biosynthesis of Geldanamycin Analogs for Hsp90 Inhibition. Chem. Biol. 2004, 11, 1625-1633.
29. Neckers, L.; Lee, Y-S. The Rules of Attraction. Nature 2003, 425, 357-359.
30. 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, 407-410.
31. Kim, J.; Felts, S.; Llaugher, L.; He, H.; Huezo, H.; Rosen, N.; Chiosis, G. Development of a Fluorescence Polarization Assay for the Molecular Chaperone Hsp90. Soc. Biomol. Screen. 2004, 9, 375-381.
32. Llauger-Bufi, L.; Felts, S.J.; Huezo, H.; Rosen, N.; Chiosis, G. Synthesis of Novel Fluorescent Probes for the Molecular Chaperone Hsp90. Bioorg. Med. Chem. Lett. 2003, 13, 3975-3978.
33. Clevenger, R.C.; Rabiel, J.M.; Peck, A.M.; Blagg, B.S.J. Biotinylated Geldanamycin. J. Org. Chem. 2004, 69, 4375-4380.
34. Zhou, V.; Han, S.; Brinker, A.; Klock, H.; Caldwell, J.; Gu, X-j. A Time-Resolved Fluorescence Resonance Energy Transfer-Based HTS Assay and a Surface Plasmon Resonance-Based Binding Assay for Heat Shock Protein 90 Inhibitors. Anal. Biochem. 2004, 331, 349-357.
35. 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 Biological Activities with Geldanamycin. Cell Stress Chaperones 1998, 3, 100-108.
36. Delmotte, P.; Delmotte-Plaque, J. A New Antifungal Substance of Fungal Origin. Nature 1953, 171, 344-345.
37. Sharma, S.V.; Agatsuma, T.; Nakano, H. Targeting of the Protein Chaperone, HSP90, by the Transformation Suppressing Agent, Radicicol. Oncogene 1998, 16, 2639-2645.
38. Chiosis, G.; Lucas, B.; Huezo, H.; Solit, D.; Basso, A.; Rosen, N. Development of Purine-Scaffold Small Molecule Inhibitors of Hsp90. Curr. Cancer Drug Targets 2003, 3, 371-376.
39. Yamamoto, K.; Garbaccio, R.M.; Stachel, S.J.; Solit, D.B.; Chiosis, G.; Rosen, N.; Danishefsky, S.J. Total Synthesis as a Resource in the Discovery of Potentially Valuable Antitumor Agents: Cycloproparadicicol. Angew. Chem. Int. Ed. 2003, 42, 1280-1284.
40. Cutler, H.G.; Arrendale, R.F.; Springer, J.P.; Cole, P.D.; Roberts, R.G.; Hanlin, R.T. Monorden from a Novel Source, Neocosmospora tenuicristata: Stereochemistry and Plant Growth Regulatory Properties. Agric. Biol. Chem. 1987, 51, 3331-3338.
41. Geng, X.; Yang Z-Q.; Danishefsky, S.J. Synthetic Development of Radicicol and Cycloproparadicicol: Highly Promising Anticancer Agents Targeting Hsp90. Synlett 2004, 8, 1325-1333.
42. Kwon, H.J.; Yoshida, M.; Fukui, Y.; Horinouchi, S.; Beppu, T. Potent and Specific Inhibitor of p60v-src Protein Kinase both In Vivo and In Vitro by Radicicol. Cancer Res. 1992, 52, 6926-6930.
43. Soga, S.; Neckers, L.M.; Schulte, T.W.; Shiotsu, Y.; Akasaka, K.; Narumi, H.; Agatsuma, T.; Ikuina, Y.; Murakata, C.; Tamaoki, T.; Akinaga, S. KF25706, a Novel Oxime Derivative of Radicicol, Exhibits In Vivo Antitumor Activity via Selective Depletion of Hsp90 Binding Signaling Molecules. Cancer Res. 1999, 59, 2931-2938.
44. Ikuina, Y.; Amishiro, N.; Miyata, M.; Narumi, H.; Ogawa, H.; Akiyama, T.; Shiotsu, Y.; Akinaga, S.; Murakata, C. Synthesis and Antitumor Activity of Novel O-Carbamoylmethyloxime Derivatives of Radicicol. J. Med. Chem. 2003, 46, 2534-2541.
45. Soga, S.; Sharma, S.; Shiotsu, Y.; Shimizu, M.; Tahara, H.; Yamaguchi, K.; Ikuina, Y.; Murakata, C.; Tamaoki, T.; Kurebayashi, J.; Schulte, T.W.; Neckers, L.M.; Skinaga, S. Stereospecific Antitumor Activity of Radicicol Oxime Derivatives. Cancer Chemother. Pharmacol. 2001, 48, 435-445.
46. Agatsuma, T.; Ogawa, H.; Akasaka, K.; Asai, A.; Yamashita, Y.; Mizukami, T.; Akinaga, S.; Saitoh, Y. Halohydrin and Oxime Derivatives of Radicicol: Synthesis and Antitumor Activities. Bioorg. Med. Chem. 2002, 10, 3445-3454.
47. Lampilas, M.; Lett, R. Convergent Stereospecific Total Synthesis of Monocillin and Monorden (or Radicicol). Tetrahedron Lett. 1992, 33, 773-780.
48. Garbaccio, R.M.; Stachel, S.J.; Baeschlin, D.K.; Danishefsky, S.J. Concise Asymmetric Synthesis of Radicicol and Monocillin I. J. Am. Chem. Soc. 2001, 23, 10903-10908.
49. Yang, Z.; Geng, X.; Solit, D.; Pratilas, C.A.; Rosen, N.; 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. 2004, 126, 7881-7889.
50. Moulin, E.; Zoete, V.; Barluenga, S.; Karplus, M.; Winssinger, N. Design, Synthesis, and Biological Evaluation of HSP90 Inhibitors Based on Conformational Analysis of Radicicol and its Analogues. J. Am. Chem. Soc. 2005, 127, 6999-7004.
51. Moulin, E.; Barluenga, S.; Winssinger, N. Concise Synthesis of Pochonin A, an HSP90 Inhibitor. Org. Lett. 2005, 7, 5637-5639.
52. 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.
53. Lee, Y-S.; Marcu, M.G.; Neckers, L.M. Quantum Chemical Calculations and Mutational Analysis Suggest Heat Shock Protein 90 Catalyzes trans-cis Isomerization of Geldanamycin. Chem. Biol. 2004, 11, 991-998.
54. Clevenger, R.C.; Blagg, B.S.J. Design, Synthesis, and Evaluation of a Radicicol and Geldanamycin Chimera, Radamide. Org. Lett. 2004, 6, 4459-4462.
55. Avila, C.; Kornilayev, B.A.; Blagg, B.S.J. Development and Optimization of a Useful Assay for Determining Hsp90's Inherent ATPase Activity. Bioorg. Med. Chem. 2006, 14, 1134-1142.
56. Shen, G.; Blagg, B.S.J. Radester, a Novel Inhibitor of the Hsp90 Protein Folding Machinery. Org. Lett. 2005, 7, 2157-2160.
57. Wang, M.; Shen, G.; Blagg, B.S.J. Radanamycin, a Macrocyclic Chimera of Radicicol and Geldanamycin. Org. Lett. 2006, in press.