Small molecule antagonists of Bcl-2 family proteins

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

Reexamination Certificate

active

07432304

ABSTRACT:
The present invention relates to naturally occurring and chemically synthesized small molecule antagonists of Bcl-2 family proteins. In particular, the present invention provides gossypol compounds (e.g., isomers, enantiomers, racemic compounds, metabolites, derivatives, pharmaceutically acceptable salts, in combination with acids or bases, and the like) and methods of using these compounds as antagonists of the anti-apoptotic effects of Bcl-2 family member proteins (e.g., Bcl-2, Bcl-XL, and the like). The present invention also provides compositions comprising gossypol compounds and optionally one or more additional therapeutic agents (e.g., anticancer/chemotherapeutic agents). The present invention also provides methods for treating diseases and pathologies (e.g., neoplastic diseases) comprising administering a composition comprising gossypol compounds and optionally one or more additional therapeutic agents (e.g., anticancer/chemotherapeutic agents) and/or techniques (e.g., radiation therapies, surgical interventions, and the like) to a subject or in vitro cells, tissues, and organs.

REFERENCES:
patent: 3347885 (1967-10-01), Jones et al.
patent: 3364242 (1968-01-01), Johnson et al.
patent: 3647791 (1972-03-01), Rossi et al.
patent: 4297341 (1981-10-01), Waller et al.
patent: 4747979 (1988-05-01), Gimber et al.
patent: 4806568 (1989-02-01), Vander Jagt et al.
patent: 5026726 (1991-06-01), Jagt et al.
patent: 5059717 (1991-10-01), Ibragimov et al.
patent: 5077441 (1991-12-01), Kuk et al.
patent: 5112637 (1992-05-01), Hron, Sr. et al.
patent: 5260327 (1993-11-01), Kim et al.
patent: 5277909 (1994-01-01), Schmidt et al.
patent: 5385936 (1995-01-01), Flack et al.
patent: 5759837 (1998-06-01), Kuhajda et al.
patent: 5780675 (1998-07-01), Royer et al.
patent: 6114397 (2000-09-01), Flack et al.
patent: 6576660 (2003-06-01), Liao et al.
patent: 6608107 (2003-08-01), Wong et al.
patent: 2002/0137801 (2002-09-01), Wong et al.
patent: 2003/0082101 (2003-05-01), Taylor et al.
patent: 2003/0119894 (2003-06-01), Murthy et al.
patent: 2005/0027000 (2005-02-01), Reed et al.
patent: 9710990 (1987-12-01), None
patent: 676360 (1988-12-01), None
patent: 87105990 (1987-12-01), None
patent: 1033795 (1989-12-01), None
patent: 1094392 (1994-11-01), None
patent: 1406919 (2001-09-01), None
patent: 1 917 341 (1969-04-01), None
patent: 0 651 636 (1993-07-01), None
patent: 01132542 (1969-04-01), None
patent: 01132542 (1987-11-01), None
patent: 1351915 (1982-06-01), None
patent: WO 94/20497 (1994-09-01), None
patent: WO 96/04250 (1996-02-01), None
patent: WO 97/40015 (1997-10-01), None
patent: WO 02/41828 (2002-05-01), None
patent: WO 02/47673 (2002-06-01), None
Merck Manual of Diagnosis and Therapy, 16th ed., 1992, pp. 1275-1277.
Shelley, et al., Anticancer Drugs, 2000;11(3):209-216.
Carter et al., Chemotherapy of Cancer 2nd ed 1981.
Johnson et al., British Journal of Cancer, 2001; 84(10):1424-1431.
V. Amberger, et al., Cancer Res., 58:149-158 (1998).
Wick et al. (W. Wick, et al., FEBS Lett., 440:419-424 (1998).
S. Mohanam, et al., Cancer Res. 53:4143-4147 (1993).
P. Pedersen, et al., Cancer Res., 53:5158-5165 (1993).
Nuria Rubio, Lab Invest, 81:725-734 (2001).
Fernández et al., Cell Death Differ., 7:350-359 (2000).
J. Reed, Nature, 387:773-776 (1997).
S. Frisch and E. Ruoslahti, Curr. Opin. Cell Biol., 9:701-706 ((1997).
D. Dell Bufalo, et al., FASEB J., 11:947-953 (1997).
Razakantoanina et al. Parasitol. Res., 86:665-668 (2000).
Dao et al. Bioorg. Med. Chem., 11:2001-2006 (2003).
Deck et al. J. Med. Chem., 34:3301-3305 (1991).
Przybylski et al. J. Mol. Structure, 611(1-3):193-201 (2002).
R.E. Royer et al., J. Med. Chem., 38:2427-2432 (1995).
R.E. Royer et al., Biologically active derivativse of gossypol: synthesis and antimalarial activities of peri-acylated gossylic nitriles:, J. Med. Chem., 29:1799-1801 (1986).
C.M. Venuti, J. Org. Chem., 46(15):3124-3127 (1981).
P.C. Meltzer et al., J. Org. Chem., 50(17):3121-3124 (1985).
R. Adams et al., J. Am. Chem. Soc., 60:2193-2204 (1938).
Le Blanc et al, “An in vitro study of inhibitory activity of gossypol, a cottonseed extract, in human carcinoma cell lines”, Pharmacol. Res., 46:551-555 (2002).
Baumgrass et al., “Reversible inhibition of calcineurin by the polyphenolic aldehyde gossypol”, J. Biol. Chem., 276:47914-47921 (2001).
Shelley et al., “Structure-activity studies on gossypol in tumor cell lines,” Anticancer Drugs, 11:209-216 (2000).
Sonenberg et al., “Anti-fertility and othe ractions of gossypol analogues”, Contraception, 37:247-255, (1988).
Whaley et al, .“Monkey lactate dehydrogenase-C4 as a model for the interaction of enzymes with gossypol”, Contraception, 33:605-616 (1986).
Dorsett et al., “Letter: Antivrial activity of gossypol and apogossypol”, J. Pharm. Sci., 64:1073-1075 (1975).
Wu et al., “Synthesis and antifertility actions of gossypol derivatives and phenol aldehydes”, Yao Xue Xue Bao, 24:502-511 (1989).
Hoffer et al., “Antifertility, spermicidal and ultrastructural effects of gossypol and derivatives administered orally and by intratesticular injections”, Contraception, 37:301-331 (1988).
Guo et al., “Synthesis of mono-aldehyde gossypol and its analogues”, Yao Xue Xue Bao, 22:597-602 (1987).
Manmade et al., “Gossypol. Synthesis and in vitro spermicidal activity of isomeric hemigossypol derivatives”, Experientia, 39:1276-1277 (1983).
Dowd, Chirality, 15:486 (2003).
Ciesielska et al., Chem. Phys. Lett. 353:69 (2002).
Vermel et al., Antitumour Activity of Gossypol in Experiments on Transplanted Tumours 39-43 (1963).
Freedman et al., Chirality, 15:196 (2003).
J.C. Reed, Pharmacology, 41:501-553 (1997).
J.C. Reed et al., J. Cell Biochem., 6:23-32 (1996).
Z. Han et al., Cancer Res., 56:621-628 (1996).
S.W. Muchmore et al., Nature, 381:335-341 (1996).
A.M. Petros et al., Protein Sci., 9:2528-2534 (2000).
A.M. Petros et al., Proc. Natl. Acad. Sci. U.S.A., 98:3012-3017 (2001).
X.M. Yin et al., Nature, 369:321-323 (1994).
S.C. Cosulich et al., Curr. Biol., 7:913-920 (1997).
A. Sali et al., Structure, Function, and Genetics, 23:318-326 (1995).
A. Sali, Curr. Opin. Biotech., 6:437-451 (1995).
J.L. Wang et al., Cancer Res., 60:1498-1502 (2000).
J.L. Wang et al., Proc. Natl. Acad. Sci. U.S.A., 97:7124-7129 (2000).
Sattler et al., Science, 275:983-986 (1997).
B.R. Brooks et al., J. Comp. Chem., 4,187-217 (1983).
P.V.R. Schleyer et al., CHARMM: The Energy Function and Its Parameterization with an Overview of the Program, in The Encyclopedia of Computational Chemistry, 1:271-277 eds., John Wiley & Sons, Chichester (1998).
S. Makino and I.D. Kuntz, J. Comput. Chem. 18:1812-1825 (1997).
I.J. Enyedy et al., J. Med. Chem., 44:313-4324 (2001).
Leschev, “Influence of the Extract ofEleutherococcus senticosuson the development of experimental pituitary adenomas in rats”, Institute of Oncology of the U.S.S.R. Academy of Medical Sciences, 60-67 (1966).
Wilsemsen, An Oxazoline-Based Approach to the Total Asymmetric Synthesis of (S)-Gossypol, UMI PROQuest Digial Disserations—Full Citation & Abstract.
La Blanc et al., An in vitro study of inhibitory activity of gossypol, a cottonseed extract, in human carcinoma cell lines, Pharmacol. Res. 46(6):551-5 (2002).
Griffith et al., Bioenvision Successfully Completes Formulation Research to Develop Gossypol as a Novel Anti-Cancer Agent, Bioenvision News (2003).
Saydachmov et al., Uebekskii Khimicheski Zhumal (1):11-13 (1994).
Zakhidov et al., Modifying Cytogenetic Effects of Gossypol and Derivatives, Library National Institutes of Health (1994).
Yerukhimov, Treatment of Bladder Tumors With Gossipol and Ionol In Combination With Surgical Intervention, Issues in Oncology, XI (1966).
Kuznezova et al., Pharmacol. Toxicol., Boston Library Boston Spa (1979).
Zhong et al., National Library of Medicine, 2:159-161 (1982).
Zhang et al., Inhibitory effects (−)-gossypol on proliferation and keratinocyte growth factor expression in human breast epithelial

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Small molecule antagonists of Bcl-2 family proteins does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Small molecule antagonists of Bcl-2 family proteins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Small molecule antagonists of Bcl-2 family proteins will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3992605

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.