CA2532148A1 - Methods to identify compounds that modulate rage - Google Patents
Methods to identify compounds that modulate rage Download PDFInfo
- Publication number
- CA2532148A1 CA2532148A1 CA002532148A CA2532148A CA2532148A1 CA 2532148 A1 CA2532148 A1 CA 2532148A1 CA 002532148 A CA002532148 A CA 002532148A CA 2532148 A CA2532148 A CA 2532148A CA 2532148 A1 CA2532148 A1 CA 2532148A1
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- compound
- rage
- gly
- fragment
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Abstract
Provided are methods to detect of modulators of the Receptor for Advanced Glycated Endproducts (RAGE). The invention comprises a method for detection of RAGE
modulators comprising: adsorbing a RAGE ligand onto a solid surface; adding a compound of interest and a protein comprising RAGE or fragment thereof, to the preadsorbed ligand;
adding an antibody which binds to RAGE or fragment thereof and a secondary antibody which binds to the anti-RAGE antibody; measuring the secondary antibody bound to the anti-RAGE antibody; and comparing the amount of RAGE bound to the ligand in the presence of varying amounts of the compound of interest. In an embodiment, the fragment of RAGE is sRAGE. In one aspect, the invention use of compounds detected by the method for treatment of AGE-related syndromes including complications associated with diabetes, kidney failure, lupus nephritis or inflammatory lupus nephritis, amyloidoses, Alzheimer's disease, cancer, inflammation, and erectile dysfunction.
modulators comprising: adsorbing a RAGE ligand onto a solid surface; adding a compound of interest and a protein comprising RAGE or fragment thereof, to the preadsorbed ligand;
adding an antibody which binds to RAGE or fragment thereof and a secondary antibody which binds to the anti-RAGE antibody; measuring the secondary antibody bound to the anti-RAGE antibody; and comparing the amount of RAGE bound to the ligand in the presence of varying amounts of the compound of interest. In an embodiment, the fragment of RAGE is sRAGE. In one aspect, the invention use of compounds detected by the method for treatment of AGE-related syndromes including complications associated with diabetes, kidney failure, lupus nephritis or inflammatory lupus nephritis, amyloidoses, Alzheimer's disease, cancer, inflammation, and erectile dysfunction.
Description
T W
LA PRESENTE PARTIE DE CETTE DEiYLWIDE OU CE BREZ'ETS
COyIPREND PLUS D'U-'( TOLYIE.
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.IIJIVL~~ A~'~LICr~.TI~NS / )PATENTS
THIS SECTION OF THE APPLICATION / P ATEN T CONTAINS uiO~, TIi.~.N ONE VOLUlYIE.
THIS IS VOLU1~IE OF
NOTE: For additional volumes please contact the Canadian Patent Office.
LA PRESENTE PARTIE DE CETTE DEiYLWIDE OU CE BREZ'ETS
COyIPREND PLUS D'U-'( TOLYIE.
CECI EST LE T01~IE ~ DE
NOTE: Pour 1es tomes additionels, veillez contacter Le Bureau Canadien des Brevets.
.IIJIVL~~ A~'~LICr~.TI~NS / )PATENTS
THIS SECTION OF THE APPLICATION / P ATEN T CONTAINS uiO~, TIi.~.N ONE VOLUlYIE.
THIS IS VOLU1~IE OF
NOTE: For additional volumes please contact the Canadian Patent Office.
2 PCT/USOi/17447 SEQDENCE LISTING
<110> Shahbaz, Manouchehr <120> Methods to Identify Compounds that Modulate Rage <130> 41305/252460 <140> US 09/799,152 <141> 2001-03-05 <150> 60/20?,342 <151> 2000-05-30 <160> 4 <170> PatentIn version 3.0 <210> 1 <211> 404 <212> PRT
<213> Homo Sapiens <400> 1 Gly Ala Ala GlyThrAla Gly Trp Val Leu heu Ser Val Ala Val Leu Trp Gly Ala ValVa1Gly Gln Ile Thr Ala Ile Gly Ala Asn Arg G1u Pro Leu Val LeuLysCys Gly'AlaPro Lys Lys Pro Gln Lys Pro Arg Leu Glu Trp LysLeuAsn Gly Thr Glu Ala Lys Val Thr Arg Trp Leu WO 01/92892 PCT/IJSOll17447 Ser Pro Gln Gly Gly Gly Pro Trp Asp Ser Val Ala Arg Val Leu_Pro Asn Gly Ser Leu Phe Leu Pro Ala Val Gly Ile Gln Asp Glu Gly Ile Phe Arg Cys Gln Ala Met Asn Arg Asn Gly Lys Glu Thr Lys Ser Asn Tyr Arg Val Arg Val Tyr Gln Ile Pro Gly Lys Pro.Glu Ile Val Asp Ser Ala Ser Glu Leu Thr Ala Gly Val Pro Asn Lys Val Gly Thr Cys Val Ser Glu Gly Ser Tyr Pro Ala Gly Thr Leu Ser Trp His Leu Asp Gly Lys Pro Leu Val Pro Asn Glu Lys Gly Val Ser Val Lys Glu Gln Thr Arg Arg His Pro Glu Thr Gly Leu Phe Thr Leu Gln Ser Glu Leu Met Val Thr Pro Ala Arg Gly Gly Asp Pro Arg Pro Thr Phe Ser Cys Ser Phe Ser Pro Gly Leu Pro Arg His Arg Ala Leu Arg Thr Ala Pro Ile Gln Pro Arg Val Trp Glu Pro Val Pro Leu Glu Glu Val Gln Leu Val Val Glu Pro Glu Gly Gly Ala Val Ala Pro Gly Gly Thr Val Thr Leu Thr Cys Glu Val Pro Ala Gln Pro Ser Pro Gln Ile His Trp Met Lys Asp Gly Val Pro Leu Pro Leu Pro Pro Ser Pro Val Leu Ile Leu Pro Glu Ile Gly Pro Gln Asp Gln Gly Thr Tyr Ser Cys Val Ala Thr His Ser Ser His Gly Pro Gln Glu Ser Arg Ala Val Ser Ile Ser Ile Ile Glu Pro Gly Glu Glu Gly Pro Thr Ala Gly Ser Val Gly Gly Ser Gly Leu Gly Thr Leu Ala~Leu Ala Leu Gly Ile Leu Gly Gly Leu Gly Thr Ala Ala Leu Leu Ile Gly Val Ile Leu Trp Gln Arg Arg Gln Arg Arg Gly Glu Glu Arg Lys Ala Pro Glu Asn Gln Glu Glu Glu Glu Glu WO 01/92892 PCT/USOl/17:1-t7 Arg Ala Glu Leu Asn Gln Ser Glu Glu Pro Glu Ala Gly Glu Ser Ser Thr Gly Gly Pro <210> 2 <211> 339 <212> PRT
<213> Homo Sapiens <400>
Gly Ala Gly ThrAlaVal Gly Trp LeuVal LeuSer Leu Ala Ala Val Trp Gly Val ValGlyAla Gln Ile AlaArg IleGly Glu Ala Asn Thr Pro Leu Leu Lys,CysLys Gly Pro LysPro ProGln Arg Val Ala Lys 35 40 . 45 Leu Glu Lys LeuAsnThr Gly Thr AlaTrp LysVal Leu Trp Arg Glu Ser Pro Gly GlyGlyPro Trp Ser AlaArg ValLeu Pro Gln Asp Val Asn Gly Leu PheLeuPro Ala Gly GlnAsp GluGly Ile Ser Val Ile Phe Arg Gln AlaMetAsn Arg Gly GluThr LysSer Asn Cys Asn Lys 100 105 ~ 120 Tyr Arg Arg ValTyrGln Ile Gly ProGlu IleVal Asp Val Pro Lys Ser Ala Glu LeuThrAla Gly Pro LysVal GlyThr Cys Ser Val Asn Val Ser Gly SerTyrPro Ala Thr SerTrp HisLeu Asp Glu Gly Leu Gly Lys Leu ValProAsn Glu Gly SerVal LysGlu Gln Pro Lys Val Thr Arg His ProGluThr Gly Phe LeuGln SerGlu Leu Arg Leu Thr Met Val Pro AlaArgGly Gly Pro ProThr PheSer Cys Thr Asp Arg WO 01/92892 PCT/USOl/17=i-17 SerPheSer ProGly LeuProArgHis ArgAlaLeu Thr Pro Arg A1a IleGlnPro ArgVal TrpGluProVal ProLeuGlu GluVal GlnLeu ValValGlu ProGlu GlyGlyAlaVal AlaProGly GlyThr ValThr LeuThrCys GluVal ProAlaGlnPro SerProGln IleHis TrpMet LysAspGly ValPro LeuProLeuPro ProSerPro ValLeu IleLeu ProGluIle GlyPro GlnAspGlnGly ThrTyrSer CysVal AlaThr HisSerSer HisGly ProGlnGluSer ArgAlaVal SerIle SerIle IleGluPro GlyGlu GluGlyProThr AlaGlySer ValGly GlySer GlyLeuGly <210> 3 <211> 112 <212> PRT
<213> Homo Sapiens <400> 3 Ala Gln Asn Ile Thr Ala Arg Ile Gly Glu Pro Leu Val Leu Lys Cys Lys Gly Ala Pro Lys Lys Pro Pro Gln Arg Leu Glu Trp Lys Leu Asn Thr Gly Arg Thr Glu Ala Trp Lys Val Leu Ser Pro Gln Gly Gly Gly Pro Trp Asp Ser Val Ala Arg Val Leu Pro Asn Gly Ser Leu Phe Leu Pro Ala Val Gly Ile Gln Asp Glu Gly Ile Phe Arg Cys Gln Ala Met Asn Arg Asn Gly Lys Glu Thr Lys Ser Asn Tyr Arg Val Arg Val Tyr Gln Ile Pro Gly Lys Pro Glu Ile Val Asp Ser Ala Ser Glu Leu Thr WO 01/92892 PCT/U~U1/174-t7 <210>4 <211>30 <212>PRT
<213>Homo Sapiens <400> 4 Ala Gln Asn Ile Thr Ala Arg Ile Gly Glu Pro Leu Val Leu Lys Cys Lys Gly Ala Pro Lys Lys Pro Pro Gln Arg Leu Glu Trp Lys LA PRESENTE PARTIE DE CETTE DEiYLANDE OLT CE D1~EV'ETS
COlyIPREND PLUS D'U'N TOIYLE.
CECI EST LE TOyLE ,~ DE
NOTE: Pour tes tomes additionels, veillez contacter le Bureau Canadien des Brevets.
3~J11~~~ .~~~IC~,.TI~i~tS / PAT~EI'~TS
THIS SECTION OF THE APPLICATION I PATEN T CON T AiNS 1~IORE
TH DIY ONE YOLU11~IE.
THIS IS VOLUyIE OF
NOTE: For additional ~ioiumes niease contact the Canadian Patent Office.
<110> Shahbaz, Manouchehr <120> Methods to Identify Compounds that Modulate Rage <130> 41305/252460 <140> US 09/799,152 <141> 2001-03-05 <150> 60/20?,342 <151> 2000-05-30 <160> 4 <170> PatentIn version 3.0 <210> 1 <211> 404 <212> PRT
<213> Homo Sapiens <400> 1 Gly Ala Ala GlyThrAla Gly Trp Val Leu heu Ser Val Ala Val Leu Trp Gly Ala ValVa1Gly Gln Ile Thr Ala Ile Gly Ala Asn Arg G1u Pro Leu Val LeuLysCys Gly'AlaPro Lys Lys Pro Gln Lys Pro Arg Leu Glu Trp LysLeuAsn Gly Thr Glu Ala Lys Val Thr Arg Trp Leu WO 01/92892 PCT/IJSOll17447 Ser Pro Gln Gly Gly Gly Pro Trp Asp Ser Val Ala Arg Val Leu_Pro Asn Gly Ser Leu Phe Leu Pro Ala Val Gly Ile Gln Asp Glu Gly Ile Phe Arg Cys Gln Ala Met Asn Arg Asn Gly Lys Glu Thr Lys Ser Asn Tyr Arg Val Arg Val Tyr Gln Ile Pro Gly Lys Pro.Glu Ile Val Asp Ser Ala Ser Glu Leu Thr Ala Gly Val Pro Asn Lys Val Gly Thr Cys Val Ser Glu Gly Ser Tyr Pro Ala Gly Thr Leu Ser Trp His Leu Asp Gly Lys Pro Leu Val Pro Asn Glu Lys Gly Val Ser Val Lys Glu Gln Thr Arg Arg His Pro Glu Thr Gly Leu Phe Thr Leu Gln Ser Glu Leu Met Val Thr Pro Ala Arg Gly Gly Asp Pro Arg Pro Thr Phe Ser Cys Ser Phe Ser Pro Gly Leu Pro Arg His Arg Ala Leu Arg Thr Ala Pro Ile Gln Pro Arg Val Trp Glu Pro Val Pro Leu Glu Glu Val Gln Leu Val Val Glu Pro Glu Gly Gly Ala Val Ala Pro Gly Gly Thr Val Thr Leu Thr Cys Glu Val Pro Ala Gln Pro Ser Pro Gln Ile His Trp Met Lys Asp Gly Val Pro Leu Pro Leu Pro Pro Ser Pro Val Leu Ile Leu Pro Glu Ile Gly Pro Gln Asp Gln Gly Thr Tyr Ser Cys Val Ala Thr His Ser Ser His Gly Pro Gln Glu Ser Arg Ala Val Ser Ile Ser Ile Ile Glu Pro Gly Glu Glu Gly Pro Thr Ala Gly Ser Val Gly Gly Ser Gly Leu Gly Thr Leu Ala~Leu Ala Leu Gly Ile Leu Gly Gly Leu Gly Thr Ala Ala Leu Leu Ile Gly Val Ile Leu Trp Gln Arg Arg Gln Arg Arg Gly Glu Glu Arg Lys Ala Pro Glu Asn Gln Glu Glu Glu Glu Glu WO 01/92892 PCT/USOl/17:1-t7 Arg Ala Glu Leu Asn Gln Ser Glu Glu Pro Glu Ala Gly Glu Ser Ser Thr Gly Gly Pro <210> 2 <211> 339 <212> PRT
<213> Homo Sapiens <400>
Gly Ala Gly ThrAlaVal Gly Trp LeuVal LeuSer Leu Ala Ala Val Trp Gly Val ValGlyAla Gln Ile AlaArg IleGly Glu Ala Asn Thr Pro Leu Leu Lys,CysLys Gly Pro LysPro ProGln Arg Val Ala Lys 35 40 . 45 Leu Glu Lys LeuAsnThr Gly Thr AlaTrp LysVal Leu Trp Arg Glu Ser Pro Gly GlyGlyPro Trp Ser AlaArg ValLeu Pro Gln Asp Val Asn Gly Leu PheLeuPro Ala Gly GlnAsp GluGly Ile Ser Val Ile Phe Arg Gln AlaMetAsn Arg Gly GluThr LysSer Asn Cys Asn Lys 100 105 ~ 120 Tyr Arg Arg ValTyrGln Ile Gly ProGlu IleVal Asp Val Pro Lys Ser Ala Glu LeuThrAla Gly Pro LysVal GlyThr Cys Ser Val Asn Val Ser Gly SerTyrPro Ala Thr SerTrp HisLeu Asp Glu Gly Leu Gly Lys Leu ValProAsn Glu Gly SerVal LysGlu Gln Pro Lys Val Thr Arg His ProGluThr Gly Phe LeuGln SerGlu Leu Arg Leu Thr Met Val Pro AlaArgGly Gly Pro ProThr PheSer Cys Thr Asp Arg WO 01/92892 PCT/USOl/17=i-17 SerPheSer ProGly LeuProArgHis ArgAlaLeu Thr Pro Arg A1a IleGlnPro ArgVal TrpGluProVal ProLeuGlu GluVal GlnLeu ValValGlu ProGlu GlyGlyAlaVal AlaProGly GlyThr ValThr LeuThrCys GluVal ProAlaGlnPro SerProGln IleHis TrpMet LysAspGly ValPro LeuProLeuPro ProSerPro ValLeu IleLeu ProGluIle GlyPro GlnAspGlnGly ThrTyrSer CysVal AlaThr HisSerSer HisGly ProGlnGluSer ArgAlaVal SerIle SerIle IleGluPro GlyGlu GluGlyProThr AlaGlySer ValGly GlySer GlyLeuGly <210> 3 <211> 112 <212> PRT
<213> Homo Sapiens <400> 3 Ala Gln Asn Ile Thr Ala Arg Ile Gly Glu Pro Leu Val Leu Lys Cys Lys Gly Ala Pro Lys Lys Pro Pro Gln Arg Leu Glu Trp Lys Leu Asn Thr Gly Arg Thr Glu Ala Trp Lys Val Leu Ser Pro Gln Gly Gly Gly Pro Trp Asp Ser Val Ala Arg Val Leu Pro Asn Gly Ser Leu Phe Leu Pro Ala Val Gly Ile Gln Asp Glu Gly Ile Phe Arg Cys Gln Ala Met Asn Arg Asn Gly Lys Glu Thr Lys Ser Asn Tyr Arg Val Arg Val Tyr Gln Ile Pro Gly Lys Pro Glu Ile Val Asp Ser Ala Ser Glu Leu Thr WO 01/92892 PCT/U~U1/174-t7 <210>4 <211>30 <212>PRT
<213>Homo Sapiens <400> 4 Ala Gln Asn Ile Thr Ala Arg Ile Gly Glu Pro Leu Val Leu Lys Cys Lys Gly Ala Pro Lys Lys Pro Pro Gln Arg Leu Glu Trp Lys LA PRESENTE PARTIE DE CETTE DEiYLANDE OLT CE D1~EV'ETS
COlyIPREND PLUS D'U'N TOIYLE.
CECI EST LE TOyLE ,~ DE
NOTE: Pour tes tomes additionels, veillez contacter le Bureau Canadien des Brevets.
3~J11~~~ .~~~IC~,.TI~i~tS / PAT~EI'~TS
THIS SECTION OF THE APPLICATION I PATEN T CON T AiNS 1~IORE
TH DIY ONE YOLU11~IE.
THIS IS VOLUyIE OF
NOTE: For additional ~ioiumes niease contact the Canadian Patent Office.
Claims (15)
1. Compounds for use as modulators of RAGE, wherein said compounds are identified by steps comprising:
adsorbing a RAGE ligand onto a solid surface;
adding a compound of interest and a protein comprising RAGE comprising SEQ ID NO: 1 or a fragment thereof to the preadsorbed ligand;
adding anti-RAGE antibody which binds to RAGE protein or a fragment thereof;
determining the amount of RAGE protein or a fragment thereof bound to the ligand by measuring the amount of anti-RAGE antibody bound to the solid surface; and comparing the amount of RAGE protein or a fragment thereof bound to the ligand in the presence of varying amounts of the compound of interest.
adsorbing a RAGE ligand onto a solid surface;
adding a compound of interest and a protein comprising RAGE comprising SEQ ID NO: 1 or a fragment thereof to the preadsorbed ligand;
adding anti-RAGE antibody which binds to RAGE protein or a fragment thereof;
determining the amount of RAGE protein or a fragment thereof bound to the ligand by measuring the amount of anti-RAGE antibody bound to the solid surface; and comparing the amount of RAGE protein or a fragment thereof bound to the ligand in the presence of varying amounts of the compound of interest.
2. The compound of claim 1, wherein the RAGE fragment comprises sRAGE as defined by the amino acid sequence SEQ ID NO: 2, or a sequence substantially homologous thereto.
3. The compound of claim 1, wherein the RAGE fragment comprises the V-domain of RAGE as defined by the amino acid sequence SEQ ID NO: 3, or a sequence substantially homologous thereto.
4. The compound of claim 1, wherein the RAGE fragment comprises a fragment of the V-domain of RAGE as defined by the amino acid sequence SEQ ID NO: 4, or a sequence substantially homologous thereto.
5. The compounds of claim 1, wherein the method of identifying said compounds further comprises measuring the ability of the compound of interest to modulate the ability of RAGE, or a sequence substantially homologous thereto, to activate a cellular process.
6. The compounds of claim 5, wherein agonists comprise stimulation of a RAGE-activated cellular process and antagonists comprise inhibition of a RAGE-activated cellular process.
7. The compounds of claim 5, wherein the cellular process comprises activation of NF- cB gene transcription.
8. The compound of claim 1, wherein the compound is used to treat symptoms of diabetes and symptoms of diabetic late complications.
9. The compound of claim 1, wherein the compound is used to treat amyloidosis.
10. The compound of claim 1, wherein the compound is used to treat Alzheimer's disease.
11 The compound of claim 1, wherein the compound is used to treat cancer.
12. The compound of claim 1, wherein the compound is used to treat inflammation.
13. The compound of claim 1, wherein the compound is used to treat kidney failure .
14. The compound of claim 1, wherein the compound is used to treat systemic lupus nephritis or inflammatory lupus nephritis.
15. The compound of claim 1, wherein the compound is used to treat erectile dysfunction.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20734200P | 2000-05-30 | 2000-05-30 | |
| US60/207,342 | 2000-05-30 | ||
| US09/799,152 US6908741B1 (en) | 2000-05-30 | 2001-03-05 | Methods to identify compounds that modulate RAGE |
| US09/799,152 | 2001-03-05 | ||
| CA002379521A CA2379521C (en) | 2000-05-30 | 2001-05-30 | Methods to identify compounds that modulate rage |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002379521A Division CA2379521C (en) | 2000-05-30 | 2001-05-30 | Methods to identify compounds that modulate rage |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2532148A1 true CA2532148A1 (en) | 2001-12-06 |
Family
ID=36121817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002532148A Abandoned CA2532148A1 (en) | 2000-05-30 | 2001-05-30 | Methods to identify compounds that modulate rage |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2532148A1 (en) |
-
2001
- 2001-05-30 CA CA002532148A patent/CA2532148A1/en not_active Abandoned
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |