Protein-degrading enediynes: Library screening of Bergman cycloaromatization products

Organic Letters

Volumn 2, Issue 13, 2000, Pages 1863-1866

  Jones, Graham B ^a   Wright, Justin M ^a   Hynd, George ^a   Wyatt, Justin K ^a   Yancisin, Molly ^b   Brown, Myles A ^b  

^a NORTHEASTERN UNIVERSITY   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC ANTIBIOTIC; ESTROGEN RECEPTOR;

ARTICLE; CHEMISTRY; COMBINATORIAL CHEMISTRY; DRUG EFFECT; DRUG SCREENING; HUMAN; METABOLISM; METHODOLOGY;

ANTIBIOTICS, ANTINEOPLASTIC; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG EVALUATION, PRECLINICAL; HUMANS; RECEPTORS, ESTROGEN;

EID: 0034729598     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol005926q     Document Type: Article

References (28)

1. Xi, Z.; Goldberg I. Comprehensive Natural Products Chemistry; Barton, D. H. R., Nakanishi, K., Eds.; Pergamon: Oxford, 1999; Vol. 7, p 553.
2. Smith, A. L.; Nicolaou, K. C. J. Med. Chem. 1996, 39, 2103. Maier, M. E. Synlett 1995, 13.
3. Smith, A. L.; Nicolaou, K. C. J. Med. Chem. 1996, 39, 2103. Maier, M. E. Synlett 1995, 13.
4. Zein, N.; Solomon, W.; Casazza, A. M.; Kadow, J. F.; Krishnan, B. S.; Tun M. M.; Vyas, D. M.; Doyle, T. W. Bioorg. Med. Chem. Lett. 1993, 3, 1351. Zein, N.; Schroeder, D. R. Advances in DNA Sequence Specific Agents; Jones, G. B., Ed.; JAI Press Inc., Greenwich, CT, 1998; Vol. 3, p 201.
5. Zein, N.; Solomon, W.; Casazza, A. M.; Kadow, J. F.; Krishnan, B. S.; Tun M. M.; Vyas, D. M.; Doyle, T. W. Bioorg. Med. Chem. Lett. 1993, 3, 1351. Zein, N.; Schroeder, D. R. Advances in DNA Sequence Specific Agents; Jones, G. B., Ed.; JAI Press Inc., Greenwich, CT, 1998; Vol. 3, p 201.
6. Jones, G. B.; Plourde, G. W.; Wright, J. M. Org. Lett. 2000, 2, 811.
7. Rana, T. M.; Meares, C. F. J. Am. Chem. Soc. 1991, 113, 1859. Hoyer, D.; Cho, H.; Schultz, P. G. J. Am. Chem. Soc. 1990, 112, 3249. Cuenoud, B.; Tarasow, T. M.; Schepartz, A. Tetrahedron Lett. 1992, 33, 895. Miyake, R.; Owens, J. T.; Xu, D.; Jackson, W. M.; Meares, C. F. J. Am. Chem. Soc. 1999, 121, 7453. Kumar, C. V.; Buranaprapuk, A. J. Am. Chem. Soc. 1999, 121, 4262.
8. Rana, T. M.; Meares, C. F. J. Am. Chem. Soc. 1991, 113, 1859. Hoyer, D.; Cho, H.; Schultz, P. G. J. Am. Chem. Soc. 1990, 112, 3249. Cuenoud, B.; Tarasow, T. M.; Schepartz, A. Tetrahedron Lett. 1992, 33, 895. Miyake, R.; Owens, J. T.; Xu, D.; Jackson, W. M.; Meares, C. F. J. Am. Chem. Soc. 1999, 121, 7453. Kumar, C. V.; Buranaprapuk, A. J. Am. Chem. Soc. 1999, 121, 4262.
9. Rana, T. M.; Meares, C. F. J. Am. Chem. Soc. 1991, 113, 1859. Hoyer, D.; Cho, H.; Schultz, P. G. J. Am. Chem. Soc. 1990, 112, 3249. Cuenoud, B.; Tarasow, T. M.; Schepartz, A. Tetrahedron Lett. 1992, 33, 895. Miyake, R.; Owens, J. T.; Xu, D.; Jackson, W. M.; Meares, C. F. J. Am. Chem. Soc. 1999, 121, 7453. Kumar, C. V.; Buranaprapuk, A. J. Am. Chem. Soc. 1999, 121, 4262.
10. Rana, T. M.; Meares, C. F. J. Am. Chem. Soc. 1991, 113, 1859. Hoyer, D.; Cho, H.; Schultz, P. G. J. Am. Chem. Soc. 1990, 112, 3249. Cuenoud, B.; Tarasow, T. M.; Schepartz, A. Tetrahedron Lett. 1992, 33, 895. Miyake, R.; Owens, J. T.; Xu, D.; Jackson, W. M.; Meares, C. F. J. Am. Chem. Soc. 1999, 121, 7453. Kumar, C. V.; Buranaprapuk, A. J. Am. Chem. Soc. 1999, 121, 4262.
11. Rana, T. M.; Meares, C. F. J. Am. Chem. Soc. 1991, 113, 1859. Hoyer, D.; Cho, H.; Schultz, P. G. J. Am. Chem. Soc. 1990, 112, 3249. Cuenoud, B.; Tarasow, T. M.; Schepartz, A. Tetrahedron Lett. 1992, 33, 895. Miyake, R.; Owens, J. T.; Xu, D.; Jackson, W. M.; Meares, C. F. J. Am. Chem. Soc. 1999, 121, 7453. Kumar, C. V.; Buranaprapuk, A. J. Am. Chem. Soc. 1999, 121, 4262.
12. O'Malley, B. W.; Mol. Endocrinol. 1990, 4, 363. Evans, R. M. Science 1988, 240, 889.
13. O'Malley, B. W.; Mol. Endocrinol. 1990, 4, 363. Evans, R. M. Science 1988, 240, 889.
14. Beckwith, A. L. J.; Gerba, S. Aust. J. Chem. 1992, 45, 289.
15. Brzozowski, A. M.; Pike, A. C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J.-A.; Carlquist, M.; Nature 1997, 389, 753. Kumar, V.; Green, S.; Stack, G.; Berry, M.; Jin, J.-R.; Chambon, P. Cell 1987, 51, 941.
16. Brzozowski, A. M.; Pike, A. C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J.-A.; Carlquist, M.; Nature 1997, 389, 753. Kumar, V.; Green, S.; Stack, G.; Berry, M.; Jin, J.-R.; Chambon, P. Cell 1987, 51, 941.
17. Gao, H.; Katzenellenbogen, J. A.; Garg, R.; Mansch, C. Chem. Rev. 1999, 99, 723.
18. 3H estradiol from ligand binding domain of hERα using increasing concentrations (nM through mM) of candidate compounds at 4°C/37°C. RBA's of compounds 9-22 were all > 1 μM, 23 (0.5 μM), and 24 (0.1 μM) relative to estradiol (1 nM). Specific details of the entire screen will be published in a full account of this work.
19. Chen, H.; Lin, R. J.; Xie, W.; Wilpitz, D.; Evans, R. M. Cell 1999, 98, 675.
20. Wang, J.; DeClercq, P. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1749. Py, S.; Harwig, C. W.; Banerjee, S.; Brown, D. L.; Fallis, A. G. Tetrahedron Lett. 1998, 39, 6139.
21. Wang, J.; DeClercq, P. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1749. Py, S.; Harwig, C. W.; Banerjee, S.; Brown, D. L.; Fallis, A. G. Tetrahedron Lett. 1998, 39, 6139.
22. Jones, G. B.; Huber, R. S.; Mathews, J. E. J. Chem. Soc., Chem. Commun. 1995, 1791. Jones, G. B.; Wright, J. M.; Plourde, G. W., II; Hynd, G.; Huber, R. S.; Mathews, J. E. J. Am. Chem. Soc. 2000, 122, 1937.
23. Jones, G. B.; Huber, R. S.; Mathews, J. E. J. Chem. Soc., Chem. Commun. 1995, 1791. Jones, G. B.; Wright, J. M.; Plourde, G. W., II; Hynd, G.; Huber, R. S.; Mathews, J. E. J. Am. Chem. Soc. 2000, 122, 1937.
24. Wakeling, A. E.; Bowler, J. J. Steroid Biochem. Mol. Biol. 1992, 43, 173. Osborne, C. K.; Coronado, E.; Allred, D. C.; Wiebe, V.; DeGregorio, M. J. Natl. Cancer Inst. 1991, 83, 1477.
25. Wakeling, A. E.; Bowler, J. J. Steroid Biochem. Mol. Biol. 1992, 43, 173. Osborne, C. K.; Coronado, E.; Allred, D. C.; Wiebe, V.; DeGregorio, M. J. Natl. Cancer Inst. 1991, 83, 1477.
26. Gibson, S. E.; Hales, N. J.; Peplow, M. A. Tetrahedron Lett. 1999, 40, 1417.
27. At micromolar levels, degradation of other proteins might also be expected to compete. In a preliminary survey, trace degradation of lysozyme and bovine serum albumin is observed, whereas moderate degradation of the transcription factor FKHR is induced. The scope and selectivity of degradation induced by 28 and refined analogues will be reported in a full account of this work.
28. This work was generously supported by the National Institutes of Health [R01GM57123].