Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-28
2000-10-10
Jones, Dwayne C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514569, A01N 4342
Patent
active
061302309
ABSTRACT:
The present invention provides compositions and methods for treating an animal, preferably a human, suffering from or predisposed to a physical disorder by administering an effective amount of a composition comprising at least one RAR antagonist, preferably an RAR.alpha. antagonist, and at least one RXR agonist. The combination of an RXR agonist, which has no therapeutic effects alone, with an RAR antagonist allows the use of lower doses of the RAR antagonist than were previously thought to be efficacious; this approach obviates many of the undesirable physiological side-effects of treatment with RAR antagonists.
REFERENCES:
patent: 5399586 (1995-03-01), Davies et al.
patent: 5559248 (1996-09-01), Starrett, Jr. et al.
patent: 5702914 (1997-12-01), Evans et al.
patent: 5747661 (1998-05-01), Evans et al.
patent: 5780676 (1998-07-01), Boehm et al.
Alcalay, M., et al., "Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor .alpha. locus," Proc. Natl. Acad. Sci. USA 88(5):1977-1981 (1991).
Allenby, G., et al., "Binding of 9-cis-Retinoic Acid and All-trans-Retinoic Acid to Retinoic Acid Receptors .alpha., .beta., and .gamma.," J. Biol. Chem. 269(24):16689-16695 (1994).
Apfel, C., et al., "A retinoic acid receptor .alpha. antagonist selectively counteracts retinoic acid effects," Proc. Natl. Acad. Sci. USA 89(15):7129-7133 (1992).
Apfel, C.M., et al., "Enhancement of HL-60 Differentiation by a New Class of Retinoids with Selective Activity on Retinoid X Receptor," J. Biol. Chem. 270(51):30765-30772 (Dec. 22, 1995).
Astrom, A., et al., "Retinoic Acid and Synthetic Analogs Differentially Activate Retinoic Acid Receptor Dependent Transcription," Biochem. Biophys. Res. Comm. 173(1):339-345 (1990).
Berard, J., et al., "Lung tumors in mice expressing an antisense RAR.beta.2 transgene," FASEB J. 10:1091-1097 (Jul. 1996).
Bernard, B.A., et al., "Identification of Synthetic Retinoids with Selectivity for Human Nuclear Retinoic Acid Receptor .gamma.," Biochem. Biophys. Res. Comm. 186(2):977-983 (1992).
Bollag, W., and Holdener, E.E., "Retinoids in cancer prevention and therapy," Annals of Oncol. 3(7):513-526 (1992).
Bollag, W., et al., "Cancer Combination Chemotherapy with Retinoids: Experimental Rationale," Leukemia 8(9):1453-1457 (1994).
Bollag, W., "The retinoid revolution," FASEB J. 10:938-939 (Jul. 1996).
Bonhomme, L., et al., "Topical treatment of epidemic Kaposi's sarcoma with all-trans-retinoic acid," Annals of Oncol. 2(3):234-235 (1991).
Bourguet, W., et al., "Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-.alpha.," Nature 375:377-382 (Jun. 1, 1995).
Brand, N., et al., "Identification of a second human retinoic acid receptor," Nature 332:850-853 (1988).
Brooks III, S.C., et al., "Myeloid Differentiation and Retinoblastoma Phosphorylation Changes in HL-60 Cells Induced by Retinoic Acid Receptor- and Retinoid X Receptor-Selective Retinoic Acid Analogs," Blood 86(1):227-237 (Jan. 1, 1996).
Castaigne, S., et al., "All-Trans Retinoic Acid as a Differentiation Therapy for Acute Promyelocytic Leukemia. I. Clinical Results," Blood 76(9):1704-1709 (1990).
Chambon, P., "The retinoid signaling pathway: molecular and genetic analyses," Cell Biol. 5(2):115-125 (1994).
Chambon, P., "A decade of molecular biology of retinoic acid receptors," FASEB J. 10:940-954 (Jul. 1996).
Chang, K.-S., et al., "Rearrangement of the Retinoic Acid Receptor Gene in Acute Promyelocytic Leukemia," Leukemia 5(3):200-204 (1991).
Chen, J.-Y., et al., "RAR-specific agonist/antagonists which dissociate transactivation and AP1 transrepression inhibit anchorage-independent cell proliferation," EMBO J. 14(6):1187-1197 (Mar. 1995).
Chen, J.-Y., et al., "Two distinct actions of retinoic-receptor ligands," Nature 382:819-822 (Aug. 29, 1996).
Chen, S.-J., et al., "Rearrangements in the Second Intron of the RARA Gene Are Present in a Large Majority of Patients With Acute Promyelocytic Leukemia and Are Used as Molecular Marker for Retinoic Acid-Induced Leukemic Cell Differentiation," Blood 78(10):2696-2701 (1991).
Chen, Z., et al., "The Retinoic Acid Alpha Receptor Gene is Frequently Disrupted in its 5' Part in Chinese Patients with Acute Promyelocytic Leukemia," Leukemia 5(4):288-292 (1991).
Chiesa, F., et al., "Prevention of Local Relapses and New Localisations of Oral Leukoplakias with the Synthetic Retinoid Fenretinide (4-HPR). Preliminary Results," Oral Oncol., Eur. J. Cancer 28B(2):97-102 (1992).
Chomienne, C., et al., "All-Trans Retinoic Acid in Acute Promyelocytic Leukemias. II. In Vitro Studies: Structure-Function Relationship," Blood 76(9):1710-1717 (1990).
Chomienne, C., et al., "All-trans Retinoic Acid Modulates the Retinoic Acid Receptor-.alpha. in Promyelocytic Cells," J. Clin. Invest. 88:2150-2154 (1991).
Chomienne, C., et al., "Retinoid differentiation therapy in promyelocytic leukemia," FASEB J. 10:1025-1030 (Jul. 1996).
Costa, A., et al., "Prospects of Chemoprevention of Human Cancers with the Synthetic Retinoid Fenretinide," Cancer Res. 54(Suppl.):2032s-2037s (1994).
de The, H., et al., "The PML-RAR.alpha. Fusion mRNA Generated by the t(15;17) Translocation in Acute Promyelocytic Leukemia Encodes a Functionally Altered RAR," Cell 66:675-684 (1991).
de The, H., "Altered retinoic acid receptors," FASEB J. 10:955-960 (Jul. 1996).
Dey, A., et al., "Ligand-Dependent Occupancy of the Retinoic Acid Receptor .beta.2 Promoter In Vivo," Mol. Cell. Biol. 14(12):8191-8201 (1994).
Doucas, V., et al., "The PML-retinoic acid receptor .alpha. translocation converts the receptor from an inhibitor to a retinoic acid-dependent activator of transcription factor AP-1," Proc. Natl. Acad. Sci. USA 90:9345-9349 (1993).
Durand, B., et al., "All-Trans and 9-Cis Retinoic Acid Induction of CRABPII Transcription Is Mediated by RAR-RXR Heterodimers Bound to DR1 and DR2 Repeated Motifs," Cell 71:73-85 (1992).
Durand, B., et al., "Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity," EMBO J. 13(22):5370-5382 (1994).
Dyck, J.A., et al., "A Novel Macromolecular Structure is a Target of the Promyelocyte-Retinoic Acid Receptor Oncoprotein," Cell 76:333-343 (1994).
Eyrolles, L., et al., "Retinoid Antagonists: Molecular Design Based on the Ligand Superfamily Concept," Med. Chem. Res. 2(6):361-367 (1992).
Fisher, G.J., and Voorhees, J.J., "Molecular mechanisms of retinoid actions in skin," FASEB J. 10(9):1002-1013 (Jul. 1996).
Forman, B.M., et al., "Unique Response Pathways Are Established by Allosteric Interactions among Nuclear Hormone Receptors," Cell 81:541-550 (May 19, 1995).
Giguere, V., et al., "Identification of a receptor for the morphogen retinoic acid," Nature 330:624-629 (1987).
Giguere, V., "Retinoic Acid Receptors and Cellular Retinoid Binding Proteins: Complex Interplay in Retinoic Signaling," Endocr. Rev. 15(1):61-79 (1994).
Green, S., and Chambon, P., "Nuclear receptors enhance our understanding of transcription regulation," Trends in Genetics 4(11):309-314 (1988).
Grignani, F., et al., "The Acute Promyelocytic Leukemia-Specific PML-RAR.alpha. Fusion Protein Inhibits Differentiation and Promotes Survival of Myeloid Precursor Cells," Cell 74:423-431 (1993).
Grignani, F., et al., "Acute Promyelocytic Leukemia: From Genetics to Treatment," Blood 83(83): 10-25 (1994).
Gronemeyer, H., and Laudet, V., "Introduction: Nuclear Receptors," Protein Profile 2(11):1173-1180 (Feb. 1996).
Gudas, L.J., et al., "Cellular Biology and Biochemistry of the Retinoids," In: The Retinoids: Biology, Chemistry, and Medicine, 2nd Ed., Sporn, M.B., et al., eds., Raven Press, Ltd., New York, NY, pp. 443-520 (1994).
Hembree, J.R., et al., "Retinoid X Receptor-specific Retinoids Inhibit the Ability of Retinoic Acid Receptor-specific Retinoids to Increase the Level of Insulin-Like Growth Factor Binding Protein-3 in Human Ectocervical Epithelial Cells," Cancer Res. 56:1794-1799 (Apr. 1996).
Hong, W.K., et al., "13-cis-Retin
Chambon Pierre
Gronemeyer Hinrich
Ostrowski Jacek
Reczek Peter R.
Bristols-Myers Squibb Company
Centre National de la Recherche Scientifiques
Institut National de la Sante et de la Recherche Medicale
Jones Dwayne C.
Universite Louis Pasteur
LandOfFree
Therapeutic combinations of RAR antagonists and RXR agonists and does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Therapeutic combinations of RAR antagonists and RXR agonists and, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Therapeutic combinations of RAR antagonists and RXR agonists and will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2257230