CA2359360A1 - In vitro screening method for identifying selective binding partners for 5-ht5-receptors - Google Patents
In vitro screening method for identifying selective binding partners for 5-ht5-receptors Download PDFInfo
- Publication number
- CA2359360A1 CA2359360A1 CA002359360A CA2359360A CA2359360A1 CA 2359360 A1 CA2359360 A1 CA 2359360A1 CA 002359360 A CA002359360 A CA 002359360A CA 2359360 A CA2359360 A CA 2359360A CA 2359360 A1 CA2359360 A1 CA 2359360A1
- Authority
- CA
- Canada
- Prior art keywords
- receptors
- binding affinity
- binding
- ht1d
- partner
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000027455 binding Effects 0.000 title claims abstract 27
- 238000009739 binding Methods 0.000 title claims abstract 27
- 238000000034 method Methods 0.000 title claims abstract 13
- 108010006590 serotonin 5 receptor Proteins 0.000 title claims abstract 13
- 238000012216 screening Methods 0.000 title claims abstract 3
- 238000000338 in vitro Methods 0.000 title claims 2
- 208000019695 Migraine disease Diseases 0.000 claims abstract 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract 3
- 206010027599 migraine Diseases 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims 7
- 101100321769 Takifugu rubripes htr1d gene Proteins 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 3
- 208000032612 Glial tumor Diseases 0.000 claims 2
- 206010018338 Glioma Diseases 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 108091006027 G proteins Proteins 0.000 claims 1
- 102000030782 GTP binding Human genes 0.000 claims 1
- 108091000058 GTP-Binding Proteins 0.000 claims 1
- 102000014384 Type C Phospholipases Human genes 0.000 claims 1
- 108010079194 Type C Phospholipases Proteins 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 230000001270 agonistic effect Effects 0.000 claims 1
- 230000003491 cAMP production Effects 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 230000001413 cellular effect Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 210000003292 kidney cell Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Pain & Pain Management (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to selective binding partners for 5-HT5-receptors, methods, in particular screening methods, for identifying and characterizing such binding partners, as well as pharmaceutical compositions containing sai d binding partners and their use in the treatment of cerebrovascular diseases such as migraine.
Claims (17)
1. An in vitro screening process for the identification of compounds for the treatment of cerebrovascular disorders, which comprises determining the affinity of compounds for 5-HT5 receptors and reading out those 5-HT5 binding partners whose binding affinity for 5-HT5 receptors is greater than their binding affinity for 5-HT1D receptors.
2. The process as claimed in claim 1, where those compounds are read out whose binding affinity for 5-HT5 receptors is greater by at least the factor 2 than their binding affinity for 5-HT1D receptors.
3. The process as claimed in claim 1, where those compounds are read out whose binding affinity for 5-HT5 receptors is greater by at least the factor 5 than their binding affinity for 5-HT1D receptors.
4. The process as claimed in one of the preceding claims, where those compounds are read out whose K i value for binding to
5-HT5 receptors is also less than 10-8 M.
5. The process as claimed in one of the preceding claims, where also at least one 5-HT5 binding partner-induced action is determined.
5. The process as claimed in one of the preceding claims, where also at least one 5-HT5 binding partner-induced action is determined.
6. The process as claimed in claim 5, where those compounds are read out whose action is agonistic.
7. The process as claimed in claim 5 or claim 6, where the binding of GTP to G proteins, intracellular calcium levels, the phospholipase C activity and/or the cAMP production are determined.
8. The process as claimed in one of the preceding claims, where, for determining binding affinity and/or activity, the compounds are brought into contact with cellular systems having 5-HT5 receptors.
9. The process as claimed in claim 8, where human glioma cell lines or h5-HT5-transfected heterologous cell lines are used.
10. The process as claimed in claim 9, where h5-HT5-transfected CHO cells, h5-HT5-transfected human kidney cells, or h5-HT5-transfected C-6 glioma cells are used.
11. The use of at least one binding partner for 5-HT5 receptors whose binding affinity for 5-HT5 receptors is greater than their binding affinity for 5-HT1D receptors, for the production of an agent for the treatment of cerebrovascular disorders.
12. The use as claimed in claim 11, where the binding affinity of the binding partner for 5-HT5 receptors is greater by at least the factor 2 than its binding affinity for 5-HT1D
receptors.
receptors.
13. The use as claimed in claim 11, where the binding affinity of the binding partner for 5-HT5 receptors is greater by at least the factor 2 than its binding affinity for 5-HT1D
receptors.
receptors.
14. The use as claimed in one of claims 11 to 13, where the K i value for binding of the binding partner to 5-HT5 receptors is less than 10-8 M.
15. The use as claimed in one of claims 11 to 14, where the bin-ding partner is a 5-HT5 agonist.
16. The use as claimed in one of claims 11 to 15, for the treatment of migraine.
17. The use as claimed in claim 16, for the acute treatment of migraine.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19900674.1 | 1999-01-11 | ||
| DE19900674A DE19900674A1 (en) | 1999-01-11 | 1999-01-11 | Binding partner for 5-HT5 receptors for migraine treatment |
| PCT/EP2000/000142 WO2000041472A2 (en) | 1999-01-11 | 2000-01-11 | Binding partners for 5-ht5-receptors for the treatment of migraine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2359360A1 true CA2359360A1 (en) | 2000-07-20 |
| CA2359360C CA2359360C (en) | 2012-11-27 |
Family
ID=7893919
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2359360A Expired - Fee Related CA2359360C (en) | 1999-01-11 | 2000-01-11 | In vitro screening method for identifying selective binding partners for 5-ht5-receptors |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1144050A2 (en) |
| JP (1) | JP2002540063A (en) |
| CN (1) | CN1321635C (en) |
| AU (1) | AU2289100A (en) |
| CA (1) | CA2359360C (en) |
| DE (1) | DE19900674A1 (en) |
| MX (1) | MXPA01006986A (en) |
| WO (1) | WO2000041472A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8921406B2 (en) | 2005-08-21 | 2014-12-30 | AbbVie Deutschland GmbH & Co. KG | 5-ring heteroaromatic compounds and their use as binding partners for 5-HT5 receptors |
| US9296697B2 (en) | 2005-08-24 | 2016-03-29 | Abbott Laboratories | Hetaryl-substituted guanidine compounds and use thereof as binding partners for 5-HT5-receptors |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102004008141A1 (en) | 2004-02-19 | 2005-09-01 | Abbott Gmbh & Co. Kg | Guanidine compounds and their use as binding partners for 5-HT5 receptors |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU8770282A (en) * | 1981-08-27 | 1983-03-03 | Shaun R. Coughlin | Composition for the treatment of atherosclerosis |
| US5360735A (en) * | 1992-01-08 | 1994-11-01 | Synaptic Pharmaceutical Corporation | DNA encoding a human 5-HT1F receptor, vectors, and host cells |
| FR2693200B1 (en) * | 1992-07-01 | 1994-08-19 | Inst Nat Sante Rech Med | New polypeptides having serotonergic receptor activity, nucleic acids encoding these polypeptides and uses. |
| FR2701265B1 (en) * | 1993-02-09 | 1995-04-07 | Inst Nat Sante Rech Med | New polypeptides having serotoninergic receptor activity, nucleic acids encoding these polypeptides and uses. |
-
1999
- 1999-01-11 DE DE19900674A patent/DE19900674A1/en not_active Withdrawn
-
2000
- 2000-01-11 MX MXPA01006986A patent/MXPA01006986A/en not_active IP Right Cessation
- 2000-01-11 WO PCT/EP2000/000142 patent/WO2000041472A2/en active Application Filing
- 2000-01-11 CN CNB008046107A patent/CN1321635C/en not_active Expired - Fee Related
- 2000-01-11 EP EP00901526A patent/EP1144050A2/en not_active Ceased
- 2000-01-11 CA CA2359360A patent/CA2359360C/en not_active Expired - Fee Related
- 2000-01-11 JP JP2000593096A patent/JP2002540063A/en active Pending
- 2000-01-11 AU AU22891/00A patent/AU2289100A/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8921406B2 (en) | 2005-08-21 | 2014-12-30 | AbbVie Deutschland GmbH & Co. KG | 5-ring heteroaromatic compounds and their use as binding partners for 5-HT5 receptors |
| US9296697B2 (en) | 2005-08-24 | 2016-03-29 | Abbott Laboratories | Hetaryl-substituted guanidine compounds and use thereof as binding partners for 5-HT5-receptors |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000041472A3 (en) | 2001-10-11 |
| CN1321635C (en) | 2007-06-20 |
| JP2002540063A (en) | 2002-11-26 |
| WO2000041472A2 (en) | 2000-07-20 |
| DE19900674A1 (en) | 2000-07-13 |
| CA2359360C (en) | 2012-11-27 |
| EP1144050A2 (en) | 2001-10-17 |
| AU2289100A (en) | 2000-08-01 |
| MXPA01006986A (en) | 2002-09-18 |
| CN1342070A (en) | 2002-03-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150112 |