CA2067183A1 - Compositions for cell adhesion inhibition and methods of use - Google Patents
Compositions for cell adhesion inhibition and methods of useInfo
- Publication number
- CA2067183A1 CA2067183A1 CA 2067183 CA2067183A CA2067183A1 CA 2067183 A1 CA2067183 A1 CA 2067183A1 CA 2067183 CA2067183 CA 2067183 CA 2067183 A CA2067183 A CA 2067183A CA 2067183 A1 CA2067183 A1 CA 2067183A1
- Authority
- CA
- Canada
- Prior art keywords
- amino acid
- acid sequence
- cadherin
- cell
- cell adhesion
- 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.)
- Abandoned
Links
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41333289A | 1989-09-27 | 1989-09-27 | |
| US413,332 | 1989-09-27 | ||
| US57126790A | 1990-08-23 | 1990-08-23 | |
| US571,267 | 1990-08-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2067183A1 true CA2067183A1 (en) | 1991-03-28 |
Family
ID=27022149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2067183 Abandoned CA2067183A1 (en) | 1989-09-27 | 1990-09-13 | Compositions for cell adhesion inhibition and methods of use |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0494175A4 (ja) |
| JP (1) | JPH05500504A (ja) |
| CA (1) | CA2067183A1 (ja) |
| WO (1) | WO1991004745A1 (ja) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6033665A (en) * | 1989-09-27 | 2000-03-07 | Elan Pharmaceuticals, Inc. | Compositions and methods for modulating leukocyte adhesion to brain endothelial cells |
| US5260210A (en) * | 1989-09-27 | 1993-11-09 | Rubin Lee L | Blood-brain barrier model |
| JPH06500555A (ja) * | 1990-08-27 | 1994-01-20 | カイロン コーポレイション | 病気の処置のためのペプチドの薬物 |
| US5827819A (en) * | 1990-11-01 | 1998-10-27 | Oregon Health Sciences University | Covalent polar lipid conjugates with neurologically active compounds for targeting |
| US5543390A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Covalent microparticle-drug conjugates for biological targeting |
| US5646250A (en) * | 1992-04-17 | 1997-07-08 | Doheny Eye Institute | Cadherin polypeptides |
| EP0604603A4 (en) * | 1992-04-17 | 1996-09-25 | Doheny Eye Inst | ELEMENTS AND METHODS FOR THE PRODUCTION OF CADHERINES. |
| US5597725A (en) * | 1992-04-17 | 1997-01-28 | Doheny Eye Institute | Cadherin-specific antibodies and hybridoma cell lines |
| AU5669494A (en) * | 1992-11-17 | 1994-06-08 | Yale University | Human homolog of the e-cadherin gene and methods based thereon |
| US5798224A (en) | 1992-12-29 | 1998-08-25 | Doheny Eye Institute | Nucleic acids encoding protocadherin |
| US5643781A (en) * | 1992-12-29 | 1997-07-01 | Doheny Eye Institute | DNA encoding protocadherin-42 |
| GB9323884D0 (en) | 1993-11-19 | 1994-01-05 | Eisai London Res Lab Ltd | Physiological modulation |
| US6031072A (en) | 1996-07-12 | 2000-02-29 | Mcgill University | Compounds and methods for modulating cell adhesion |
| US7122623B2 (en) | 1996-07-12 | 2006-10-17 | Adherex Technologies, Inc. | Compounds and methods for modulating cell adhesion |
| US6562786B1 (en) | 1996-07-12 | 2003-05-13 | Mcgill University | Compounds and methods for modulating apoptosis |
| US6417325B1 (en) | 1996-07-12 | 2002-07-09 | Mcgill University | Compounds and methods for cancer therapy |
| US6465427B1 (en) | 1996-07-12 | 2002-10-15 | Mcgill University | Compounds and methods for modulating cell adhesion |
| US6207639B1 (en) | 1996-07-12 | 2001-03-27 | Mcgill University | Compounds and methods for modulating neurite outgrowth |
| US6610821B1 (en) | 1996-07-12 | 2003-08-26 | Mcgill University | Compounds and methods for modulating endothelial cell adhesion |
| US6169071B1 (en) | 1996-07-12 | 2001-01-02 | Mcgill University | Compounds and methods for modulating cell adhesion |
| US6346512B1 (en) | 1996-07-12 | 2002-02-12 | Mcgill University | Compounds and methods for modulating cell adhesion |
| US6333307B1 (en) * | 1996-07-12 | 2001-12-25 | Mcgill University | Compounds and method for modulating neurite outgrowth |
| US20020168761A1 (en) | 2000-01-24 | 2002-11-14 | Gour Barbara J. | Peptidomimetic modulators of cell adhesion |
| US6551994B1 (en) * | 1997-04-10 | 2003-04-22 | Mcgill University | Compounds and methods for inhibiting the interaction between α-catenin and β-catenin |
| US6203788B1 (en) | 1997-09-29 | 2001-03-20 | Adherex Inc. | Compounds and methods for regulating cell adhesion |
| US6680175B2 (en) | 1998-05-05 | 2004-01-20 | Adherex Technologies, Inc. | Methods for diagnosing and evaluating cancer |
| US6472367B1 (en) | 1998-05-05 | 2002-10-29 | Adherex Technologies, Inc. | Compounds and methods for modulating OB-cadherin mediated cell adhesion |
| US7481999B2 (en) | 1998-05-05 | 2009-01-27 | Adherex Technologies, Inc. | Compounds and methods for modulating OB-cadherin-mediated function |
| US6638911B1 (en) | 1998-05-05 | 2003-10-28 | Adherex Technologies Inc. | Compounds and methods for modulating desmosomal cadherin-mediated functions |
| WO1999057149A2 (en) * | 1998-05-05 | 1999-11-11 | Adherex Technologies, Inc. | Compounds and methods for modulating nonclassical cadherin-mediated functions |
| WO2000001418A1 (en) | 1998-07-02 | 2000-01-13 | Genzyme Corporation | Transgene expression in polarized cells |
| US6277824B1 (en) | 1998-07-10 | 2001-08-21 | Adherex Technologies | Compounds and methods for modulating adhesion molecule function |
| AU4417000A (en) * | 1999-04-15 | 2000-11-02 | Glaxo Group Limited | Novel pharmaceutical composition suitable for gene therapy |
| AU2001258659A1 (en) * | 2000-05-30 | 2001-12-11 | Ich Productions Limited | Improved methods of transfection |
| AU2003298475A1 (en) | 2002-11-14 | 2004-06-18 | Adherex Technologies, Inc. | Compounds and methods for modulating desmosomal and atypical cadherin-mediated cell adhesion |
| US7244764B2 (en) | 2003-06-23 | 2007-07-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| US7414076B2 (en) | 2003-06-23 | 2008-08-19 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| EP1768687A2 (en) | 2004-06-29 | 2007-04-04 | Massachusetts Institute Of Technology | Methods and compositions related to the modulation of intercellular junctions |
| WO2006085149A2 (en) | 2004-12-22 | 2006-08-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| CA2763671A1 (en) | 2005-04-26 | 2006-11-02 | Pfizer Inc. | P-cadherin antibodies |
| PT2089417E (pt) | 2006-10-12 | 2015-04-14 | Bhi Ltd Partnership | Métodos, compostos, composições e veículos para administrar o ácido 3-amino-1-propanossulfónico |
| EP2342356A4 (en) | 2008-09-29 | 2012-11-21 | Univ Ben Gurion | AMYLOID BETA PEPTIDASES AND METHOD OF USE THEREOF |
| CA2925487C (en) | 2013-09-24 | 2023-11-07 | University Of Washington Through Its Center For Commercialization | Desmoglein 2 (dsg2) binding proteins and uses therefore in treating disorders associated with epithelial tissues |
| US20190271703A1 (en) * | 2016-10-26 | 2019-09-05 | Duke University | Biomarkers and treatments for metastatic cancer |
| CN110997693A (zh) | 2017-06-07 | 2020-04-10 | 阿德克斯公司 | τ聚集抑制剂 |
| US11453701B2 (en) | 2017-08-18 | 2022-09-27 | Adrx, Inc. | Tau aggregation peptide inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4671958A (en) * | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
| US4866042A (en) * | 1987-11-18 | 1989-09-12 | Neuwelt Edward A | Method for the delivery of genetic material across the blood brain barrier |
-
1990
- 1990-09-13 JP JP2512779A patent/JPH05500504A/ja active Pending
- 1990-09-13 CA CA 2067183 patent/CA2067183A1/en not_active Abandoned
- 1990-09-13 EP EP19900913684 patent/EP0494175A4/en not_active Withdrawn
- 1990-09-13 WO PCT/US1990/005105 patent/WO1991004745A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP0494175A1 (en) | 1992-07-15 |
| WO1991004745A1 (en) | 1991-04-18 |
| EP0494175A4 (en) | 1993-05-05 |
| JPH05500504A (ja) | 1993-02-04 |
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