WO1994017796B1 - Therapeutic use of compounds having selective agonist-like activity on rxr retinoid receptors - Google Patents
Therapeutic use of compounds having selective agonist-like activity on rxr retinoid receptorsInfo
- Publication number
- WO1994017796B1 WO1994017796B1 PCT/US1994/001579 US9401579W WO9417796B1 WO 1994017796 B1 WO1994017796 B1 WO 1994017796B1 US 9401579 W US9401579 W US 9401579W WO 9417796 B1 WO9417796 B1 WO 9417796B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- active compound
- diseases
- receptor sites
- retinoid receptor
- retinoid
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract 22
- 230000000694 effects Effects 0.000 title claims 10
- 102000027730 retinoid hormone receptors Human genes 0.000 title 1
- 108091008001 retinoid hormone receptors Proteins 0.000 title 1
- 230000001225 therapeutic Effects 0.000 title 1
- 201000010099 disease Diseases 0.000 claims abstract 16
- 238000000034 method Methods 0.000 claims abstract 10
- 102000034577 retinoid X receptors Human genes 0.000 claims abstract 9
- 102000003702 retinoic acid receptors Human genes 0.000 claims abstract 8
- 241000124008 Mammalia Species 0.000 claims abstract 7
- 239000000556 agonist Substances 0.000 claims abstract 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 7
- 230000003211 malignant Effects 0.000 claims 7
- 230000003463 hyperproliferative Effects 0.000 claims 6
- 206010003210 Arteriosclerosis Diseases 0.000 claims 4
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims 4
- 206010013774 Dry eye Diseases 0.000 claims 4
- 206010058108 Dyslipidaemia Diseases 0.000 claims 4
- 206010021425 Immune system disease Diseases 0.000 claims 4
- 210000003491 Skin Anatomy 0.000 claims 4
- 201000001320 atherosclerosis Diseases 0.000 claims 4
- 230000001684 chronic Effects 0.000 claims 4
- 200000000018 inflammatory disease Diseases 0.000 claims 4
- 230000001737 promoting Effects 0.000 claims 4
- 200000000008 restenosis Diseases 0.000 claims 4
- 230000029663 wound healing Effects 0.000 claims 4
- 206010003816 Autoimmune disease Diseases 0.000 claims 3
- 208000006641 Skin Disease Diseases 0.000 claims 3
- 230000037356 lipid metabolism Effects 0.000 claims 3
- 150000004492 retinoid derivatives Chemical class 0.000 claims 3
- 230000037396 body weight Effects 0.000 claims 2
- 238000004166 bioassay Methods 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
Abstract
Process of treatment of mammals, including humans to treat diseases or conditions of the type which are normally treated with retinoid-like compounds is disclosed, with pharmaceutical compositions containing an active compound which is a selective agonist of the RXR retinoid receptor sites in preference to the RAR retinoid receptor sites. A compound is defined to be a selective agonist of the RXR receptor site if the compound is at least approximately ten times more effective as an agonist in the RXR receptor sites than in the RAR receptor sites.
Claims
1. (AMENDED) A process for administering to a host mammal, including a human being, a pharmaceutical composition containing an effective dose of an active compound to treat or prevent one or more of the diseases and conditions selected from the group consisting of atherosclerosis and restenosis resulting from neointimal hyperproliferation, non-malignant hyperproliterative diseases, immunological disorders, chronic inflammatory diseases, diseases associated with lipid transport such as dyslipidemias, dry eye syndrome, for promoting wound healing, and for reversing and preventing the effects of sun damage to skin wherein the active compound has retinoid like activity and is a selective agonist of RXR retinoid receptor sites in preference over RAR retinoid receptor sites.
2. The process of Claim 1 wherein the active compound binds at least approximately ten times stronger to RXR retinoid receptor sites than to RAR retinoid receptor sites.
3. The process of Claim 2 wherein approximately 0.01 to 100 mg/kg body weight of the active compound is administered systemically to the host mammal per day.
4. The process of Claim 3 wherein approximately 0.1 to 10 mg/kg body weight of the active compound is administered systemically to the host mammal per day.
5. (AMENDED) A process for administering to a host female mammal, including a female human being who is in child bearing age or pregnant, a pharmaceutical composition containing an effective dose of an active compound to treat or prevent one or more of the diseases and conditions selected from the group consisting of dermatoses, malignant hyperproliferative diseases, atherosclerosis and restenosis resulting from neointimal hyperproliferation, non-malignant hyperproliferative diseases autoimmune diseases, immunological disorders, chronic inflammatory diseases, diseases associated with lipid metabolism and transport such as dyslipidemias, dry eye syndrome, for promoting wound healing, and for reversing and preventing the effects of sun damage to skin wherein the active compound has retinoid like activity and is a selective agonist of RXR retinoid receptor sites in preference over RAR retinoid receptor sites.
6. The process of Claim 2 wherein the active compound is administered topically in a pharmaceutical composition where the active compound is present in a concentration approximately between 0.001 to 5.0 per cent by weight.
7. The process of Claim 6 wherein the active compound is administered topically in a pharmaceutical composition where the active compound is present in a concentration approximately between 0.01 to 1.0 per cent by weight.
8. (AMENDED) A process for administering topically to a host female mammal, including a female human being who is in child bearing age or pregnant, a pharmaceutical composition containing an effective dose of an active compound present in a concentration approximately between 0.001 to 5.0 per cent by weight, to treat or prevent one or more of the diseases and conditions selected from the group consisting of dermatoses, malignant hyperproliferative diseases, atherosclerosis and restenosis resulting from neointimal hyperproliferation, non-malignant hyperproliferative diseases autoimmune diseases, immunological disorders, chronic inflammatory diseases, diseases associated with lipid metabolism and transport such as dyslipidemias, dry eye syndrome, for promoting wound healing, and for reversing and preventing the effects of sun damage to skin wherein the active compound has retinoid like activity and binds at least approximately ten times stronger to RXR retinoid receptor sites than to RAR retinoid receptor sites.
9. (AMENDED) A process for administering to a host mammal, including a human being, a pharmaceutical composition containing an effective dose of an active compound having retinoid-like biological activity, to treat or prevent one or more of the diseases and conditions selected from the group consisting of dermatoses, malignant hyperproliferative diseases, atherosclerosis and restenosis resulting from neointimal hyperproliferation, non-malignant hyperproliferative diseases autoimmune diseases, immunological disorders, chronic inflammatory diseases, diseases associated with lipid metabolism and transport such as dyslipidemias, dry eye syndrome, for promoting wound healing, and for reversing the preventing the effects of sun damage to skin wherein the active compound has the biological property that the compound is a selective agonist of RXR retinoid receptor sites in preference over RAR retinoid receptor sites, and wherein in an assay conducted to measure the agonist¬ like binding activity of the active compound to RAR and RXR receptor sites,
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002155828A CA2155828A1 (en) | 1993-02-11 | 1994-02-10 | Therapeutic use of compounds having selective agonist-like activity on rxr retinoid receptors |
BR9405721A BR9405721A (en) | 1993-02-11 | 1994-02-10 | Therapeutic use of compounds with selective agonist-like activity on retinoid rxr receptors |
EP94909614A EP0682516A1 (en) | 1993-02-11 | 1994-02-10 | Therapeutic use of compounds having selective agonist-like activity on rxr retinoid receptors |
JP6518387A JPH08506816A (en) | 1993-02-11 | 1994-02-10 | Pharmaceutical use of compounds having selective agonist-like activity for RXR retinoid receptor |
AU62395/94A AU693434B2 (en) | 1993-02-11 | 1994-02-10 | Therapeutic use of compounds having selective agonist-like activity on RXR retinoid receptors |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/016,404 US5455265A (en) | 1993-02-11 | 1993-02-11 | Method of treatment with compounds having selective agonist-like activity on RXR retinoid receptors |
US08/016,404 | 1993-02-11 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1994017796A1 WO1994017796A1 (en) | 1994-08-18 |
WO1994017796B1 true WO1994017796B1 (en) | 1994-10-27 |
Family
ID=21776957
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1994/001579 WO1994017796A1 (en) | 1993-02-11 | 1994-02-10 | Therapeutic use of compounds having selective agonist-like activity on rxr retinoid receptors |
Country Status (7)
Country | Link |
---|---|
US (2) | US5455265A (en) |
EP (1) | EP0682516A1 (en) |
JP (1) | JPH08506816A (en) |
AU (1) | AU693434B2 (en) |
BR (1) | BR9405721A (en) |
CA (1) | CA2155828A1 (en) |
WO (1) | WO1994017796A1 (en) |
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1994
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- 1994-02-10 CA CA002155828A patent/CA2155828A1/en not_active Abandoned
- 1994-02-10 WO PCT/US1994/001579 patent/WO1994017796A1/en not_active Application Discontinuation
- 1994-02-10 JP JP6518387A patent/JPH08506816A/en not_active Ceased
- 1994-02-10 AU AU62395/94A patent/AU693434B2/en not_active Ceased
- 1994-02-10 BR BR9405721A patent/BR9405721A/en not_active Application Discontinuation
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1995
- 1995-04-20 US US08/425,558 patent/US6627652B1/en not_active Expired - Fee Related
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