EP1671129A1 - Composes et methodes pour favoriser l'angiogenese, au moyen d'un inhibiteur de la gamma secretase et en inhibant la voie de la gamma secretase - Google Patents

Composes et methodes pour favoriser l'angiogenese, au moyen d'un inhibiteur de la gamma secretase et en inhibant la voie de la gamma secretase

Info

Publication number
EP1671129A1
EP1671129A1 EP04749182A EP04749182A EP1671129A1 EP 1671129 A1 EP1671129 A1 EP 1671129A1 EP 04749182 A EP04749182 A EP 04749182A EP 04749182 A EP04749182 A EP 04749182A EP 1671129 A1 EP1671129 A1 EP 1671129A1
Authority
EP
European Patent Office
Prior art keywords
gamma
secretase
angiogenesis
cells
group
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.)
Withdrawn
Application number
EP04749182A
Other languages
German (de)
English (en)
Inventor
Mats HELLSTRÖM
Linda Karlsson
Elisabet Wallgard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bioinvent International AB
Original Assignee
Angiogenetics Sweden AB
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from SE0302111A external-priority patent/SE0302111D0/xx
Application filed by Angiogenetics Sweden AB filed Critical Angiogenetics Sweden AB
Publication of EP1671129A1 publication Critical patent/EP1671129A1/fr
Withdrawn legal-status Critical Current

Links

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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase

Definitions

  • a method of influencing a disease state in a cell, a group of cells, or an organism comprises administering at least one of a gamma-secretase inhibitor or a gamma-secretase pathway inhibitor to the cell, group of cells, or organism.
  • the disease thus influenced can be selected from the group consisting of atherosclerosis, hemangioma, hemangioendothelioma, vascular malformations, warts, pyogenic granulomas, hair growth, Kaposi's sarcoma, scar keloids, allergic edema, neoplasms, psoriasis, decubitus or stasis ulcers, gastrointestinal ulcers, dysfunctional uterine bleeding, follicular cysts, ovarian hyperstimulation, endometriosis, neoplasms, preeclampsia, placental insufficiency, respiratory distress, ascites, peritoneal sclerosis, adhesion formation, metastatic spreading, coronary artery disease, ischemic heart disease, ischemic limb disease, obesity, rheumatoid arthritis, synovitis, bone destruction, cartilage destruction, osteomyelitis, pannus growth, osterphyte formation, cancer, as
  • a method for screening for a substance which initiates or increases angiogenesis comprises measuring an activity of the gamma-secretase pathway in the presence of a candidate compound, measuring an activity of the gamma-secretase pathway in the absence of a candidate compound, and then comparing the activity measured in the presence of a candidate compound with the activity measured in the absence of the candidate compound. A change in activity indicates that that candidate initiates or increases angiogenesis.
  • Figure 12 depicts quantitative measurements of VEGF-A levels in mouse retinas
  • Figure 16 shows vascularization of a treated mouse retina.
  • mice employed murine cells or tissues because they provided a convenient way to analyze factors upregulated in mammalian embryos.
  • inventive methods and compositions are also applicable to other mammals including, but not limited to, mice, rats, rabbits, dogs, pigs, and humans.
  • murine models have been extrapolated to Alzheimer's in humans.
  • C. elegans and Drosophila species have been used to elucidate Alzheimer's related pathways with good reproducibility in mice.
  • the close homology between mammalian genes when compared to the non-mammal models is further evidence that the data from one species of mammal is applicable to other mammals.
  • Total perfusion area is calculated using the total sum of the side branch luminal areas.
  • Capillary density is determined by immunostaining for thrombomodulin.
  • Wall thickness of fully SMC-covered vessels is morphometrically measured on histological sections, after smooth muscle -x-actin staining. For all treatment groups, six cross- sections (150 ⁇ m apart) are analyzed per main collateral. Only second-generation collateral arterioles larger than 300 ⁇ m 2 are included in the analysis. At least 10 measurements of wall thickness of the second-generation collateral arterioles are obtained. See, generally, Luttun A, et al, Aug 2002, Revascularization of ischemic tissues by PIGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Fltl., Nat Med.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Food Science & Technology (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'angiogenèse peut être déclenchée ou augmentée, par l'utilisation d'inhibiteurs de la gamma sécrétase. L'inhibiteur de la gamma sécrétase DAPT peut déclencher et augmenter l'angiogenèse. L'invention concerne des méthodes permettant de déclencher et d'augmenter l'angiogenèse. Ces méthodes sont utilisées pour prévenir et pour traiter une maladie, ainsi que pour générer des modèles de recherche.
EP04749182A 2003-07-21 2004-07-21 Composes et methodes pour favoriser l'angiogenese, au moyen d'un inhibiteur de la gamma secretase et en inhibant la voie de la gamma secretase Withdrawn EP1671129A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US48834503P 2003-07-21 2003-07-21
SE0302111A SE0302111D0 (sv) 2003-07-21 2003-07-21 Compounds and methods for inhibiting or promoting angiogenesis field of the invention
PCT/SE2004/001146 WO2005008250A1 (fr) 2003-07-21 2004-07-21 Composes et methodes pour favoriser l'angiogenese, au moyen d'un inhibiteur de la gamma secretase et en inhibant la voie de la gamma secretase

Publications (1)

Publication Number Publication Date
EP1671129A1 true EP1671129A1 (fr) 2006-06-21

Family

ID=34082463

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04749182A Withdrawn EP1671129A1 (fr) 2003-07-21 2004-07-21 Composes et methodes pour favoriser l'angiogenese, au moyen d'un inhibiteur de la gamma secretase et en inhibant la voie de la gamma secretase

Country Status (2)

Country Link
EP (1) EP1671129A1 (fr)
WO (1) WO2005008250A1 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7521481B2 (en) 2003-02-27 2009-04-21 Mclaurin Joanne Methods of preventing, treating and diagnosing disorders of protein aggregation
EP1666068A4 (fr) * 2003-09-24 2010-08-04 Santen Pharmaceutical Co Ltd Remede pour maladies des yeux accompagnees de blessures du nerf optique
GB0525214D0 (en) 2005-12-12 2006-01-18 Bioinvent Int Ab Biological materials and uses thereof
WO2007103114A2 (fr) 2006-03-07 2007-09-13 The Brigham & Women's Hospital, Inc. Inhibition de notch dans le traitement ou la prévention d'athérosclérose
US9567396B2 (en) 2006-03-07 2017-02-14 Evonik Degussa Gmbh Notch inhibition in the prevention of vein graft failure
US20100226922A1 (en) * 2006-06-08 2010-09-09 Dorothea Maetzel Specific protease inhibitors and their use in cancer therapy
EP1865001A1 (fr) * 2006-06-08 2007-12-12 Gsf-Forschungszentrum Für Umwelt Und Gesundheit, Gmbh Inhibiteurs spécifiques de protéase et leur utilisation dans la thérapie de cancer
WO2008055945A1 (fr) 2006-11-09 2008-05-15 Probiodrug Ag Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies
US9126987B2 (en) 2006-11-30 2015-09-08 Probiodrug Ag Inhibitors of glutaminyl cyclase
CN101668525A (zh) 2007-03-01 2010-03-10 前体生物药物股份公司 谷氨酰胺酰环化酶抑制剂的新用途
EP2865670B1 (fr) 2007-04-18 2017-01-11 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
US8343923B2 (en) * 2007-11-09 2013-01-01 Washington University Use of notch signaling regulators for modulating osteogenesis
EP2475428B1 (fr) 2009-09-11 2015-07-01 Probiodrug AG Dérivés hétérocycliques en tant qu'inhibiteurs de glutaminyle cyclase
EP2493497A4 (fr) 2009-11-01 2013-07-24 Brigham & Womens Hospital Inhibition de notch pour le traitement et la prévention de l'obésité et du syndrome métabolique
US9181233B2 (en) 2010-03-03 2015-11-10 Probiodrug Ag Inhibitors of glutaminyl cyclase
AU2011226074B2 (en) 2010-03-10 2015-01-22 Vivoryon Therapeutics N.V. Heterocyclic inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
KR101330184B1 (ko) 2010-10-15 2013-11-15 성균관대학교산학협력단 감마-세크레타제 저해제를 유효성분으로 함유하는 류마티스성 관절염의 예방 또는 치료용 조성물
DK2686313T3 (en) 2011-03-16 2016-05-02 Probiodrug Ag Benzimidazole derivatives as inhibitors of glutaminyl cyclase
DK3461819T3 (da) 2017-09-29 2020-08-10 Probiodrug Ag Inhibitorer af glutaminylcyklase

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004073630A2 (fr) * 2003-02-18 2004-09-02 Roskamp Research Llc Proprietes anti-angiogeniques et antitumorales des inhibiteurs de beta-secretase et de gamma-secretase

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020151487A1 (en) * 2000-08-31 2002-10-17 Loyola University Chicago Method and reagents for epithelial barrier formation and treatment of malignant and benign skin disorders by modulating the notch pathway

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004073630A2 (fr) * 2003-02-18 2004-09-02 Roskamp Research Llc Proprietes anti-angiogeniques et antitumorales des inhibiteurs de beta-secretase et de gamma-secretase

Also Published As

Publication number Publication date
WO2005008250A1 (fr) 2005-01-27

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