WO1999043308A3 - Treating pulmonary hypertension through tenascin suppression and elastase inhibition - Google Patents
Treating pulmonary hypertension through tenascin suppression and elastase inhibition Download PDFInfo
- Publication number
- WO1999043308A3 WO1999043308A3 PCT/IB1999/000413 IB9900413W WO9943308A3 WO 1999043308 A3 WO1999043308 A3 WO 1999043308A3 IB 9900413 W IB9900413 W IB 9900413W WO 9943308 A3 WO9943308 A3 WO 9943308A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tenascin
- pulmonary hypertension
- suppression
- treating pulmonary
- elastase inhibition
- Prior art date
Links
- 102000007000 Tenascin Human genes 0.000 title abstract 3
- 108010008125 Tenascin Proteins 0.000 title abstract 3
- 208000002815 pulmonary hypertension Diseases 0.000 title abstract 3
- 102000016387 Pancreatic elastase Human genes 0.000 title abstract 2
- 108010067372 Pancreatic elastase Proteins 0.000 title abstract 2
- 230000005764 inhibitory process Effects 0.000 title abstract 2
- 230000001629 suppression Effects 0.000 title 1
- 229940122858 Elastase inhibitor Drugs 0.000 abstract 2
- 239000003602 elastase inhibitor Substances 0.000 abstract 2
- 102000002149 Elafin Human genes 0.000 abstract 1
- 108010015972 Elafin Proteins 0.000 abstract 1
- 229930064664 L-arginine Natural products 0.000 abstract 1
- 235000014852 L-arginine Nutrition 0.000 abstract 1
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 abstract 1
- 230000004663 cell proliferation Effects 0.000 abstract 1
- MDCUNMLZLNGCQA-HWOAGHQOSA-N elafin Chemical group N([C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H]1C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H]2CSSC[C@H]3C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CSSC[C@H]4C(=O)N5CCC[C@H]5C(=O)NCC(=O)N[C@H](C(N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]5N(CCC5)C(=O)[C@H]5N(CCC5)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC2=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N4)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N3)=O)[C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)N MDCUNMLZLNGCQA-HWOAGHQOSA-N 0.000 abstract 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A method for treating pulmonary hypertension is described comprising administering an elastase inhibitor to a patient. Inhibition of elastase suppresses tenascin, which leads to a reduction of the smooth muscle cell proliferation associated with pulmonary hypertension. More specifically, the tenascin suppressant is L-arginine and the elastase inhibitor is elafin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7618998P | 1998-02-27 | 1998-02-27 | |
| US60/076,189 | 1998-02-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1999043308A2 WO1999043308A2 (en) | 1999-09-02 |
| WO1999043308A3 true WO1999043308A3 (en) | 1999-10-28 |
Family
ID=22130483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB1999/000413 WO1999043308A2 (en) | 1998-02-27 | 1999-02-26 | Treating pulmonary hypertension through tenascin suppression and elastase inhibition |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1999043308A2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6849605B1 (en) | 1999-03-05 | 2005-02-01 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of viral infections |
| US7704958B1 (en) | 1999-03-05 | 2010-04-27 | Bio Holding, Inc. | Methods and compositions for inhibiting apoptosis using serine protease inhibitors |
| CA2833559A1 (en) | 2003-02-14 | 2004-09-02 | Children's Hospital & Research Center At Oakland | Treatment of conditions associated with decreased nitric oxide bioavailability, including elevated arginase conditions |
| CA2587647C (en) | 2004-12-01 | 2017-03-28 | Children's Hospital & Research Center At Oakland | Diagnosis of conditions associated with decreased arginine bioavailability |
| FR2930036B1 (en) * | 2008-04-11 | 2010-05-07 | Assist Publ Hopitaux De Paris | METHOD FOR DIAGNOSING PULMONARY ARTERIAL HYPERTENSION |
| JP2017530954A (en) * | 2014-08-26 | 2017-10-19 | プロテオ バイオテック アーゲー | Use of elafin for disorders associated with an increase independent of troponin elastase |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995009636A1 (en) * | 1993-10-04 | 1995-04-13 | The Trustees Of Columbia University In The City Ofnew York | Method of inducing vasorelaxation to treat pulmonary hypertension |
| WO1998008500A1 (en) * | 1996-08-26 | 1998-03-05 | Board Of Regents, The University Of Texas System | Hypertonic arginine compositions and methods |
| WO1999017800A1 (en) * | 1997-10-03 | 1999-04-15 | Amgen Inc. | Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions |
| US5895788A (en) * | 1996-01-31 | 1999-04-20 | The Board Of Trustees Of The University Of Arkansas | Use of L-arginine and salts thereof in drinking water for the prevention and/or treatment of pulmonary hypertension syndrome in avians |
-
1999
- 1999-02-26 WO PCT/IB1999/000413 patent/WO1999043308A2/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995009636A1 (en) * | 1993-10-04 | 1995-04-13 | The Trustees Of Columbia University In The City Ofnew York | Method of inducing vasorelaxation to treat pulmonary hypertension |
| US5895788A (en) * | 1996-01-31 | 1999-04-20 | The Board Of Trustees Of The University Of Arkansas | Use of L-arginine and salts thereof in drinking water for the prevention and/or treatment of pulmonary hypertension syndrome in avians |
| WO1998008500A1 (en) * | 1996-08-26 | 1998-03-05 | Board Of Regents, The University Of Texas System | Hypertonic arginine compositions and methods |
| WO1999017800A1 (en) * | 1997-10-03 | 1999-04-15 | Amgen Inc. | Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions |
Non-Patent Citations (8)
| Title |
|---|
| ADNOT, S. ET AL: "Loss of endothelium-dependent relaxation during chronic hypoxic pulmonary hypertension: Recovery on return to room air or after treatment with L-arginine", BIOL. NITRIC OXIDE, PROC. INT. MEET., 2ND (1992), MEETING DATE 1991, VOLUME 1, 32-4. EDITOR(S): MONCADA, SALVADOR. PUBLISHER: PORTLAND PRESS, LONDON, UK., XP002113476 * |
| BOEGER, R. H. (1) ET AL: "Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension.", INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, (1996) VOL. 34, NO. 8, PP. 323-328., XP002113471 * |
| GOSSAGE J R ET AL: "THE NEUTROPHIL ELASTASE INHIBITOR SC-39026 ALTERS THE DEVELOPMENT OF SUSTAINED PULMONARY HYPERTENSION SECONDARY TO CONTINUOUS AIR EMBOLIZATION (CAE).", 1991 INTERNATIONAL CONFERENCE OF THE AMERICAN LUNG ASSOCIATION AND THE AMERICAN THORACIC SOCIETY, ANAHEIM, CALIFORNIA, USA, MAY 12-15, 1991. AM REV RESPIR DIS. (1991) 143 (4 PART 2), A187., XP002113475 * |
| MCCAFFREY, MARTIN J. ET AL: "Effect of L-arginine infusion of infants with persistent pulmonary hypertension of the newborn.", PEDIATRIC RESEARCH, (1994) VOL. 37, NO. 4 PART 2, PP. 341A. MEETING INFO.: 105TH ANNUAL MEETING OF THE AMERICAN PEDIATRIC SOCIETY AND THE 64TH ANNUAL MEETING OF THE SOCIETY FOR PEDIATRIC RESEARCH SAN DIEGO, CALIFORNIA, USA MAY 7-11, 1995, XP002113470 * |
| MEHTA S. ET AL: "Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension.", CIRCULATION, (1995) 92/6 (1539-1545)., XP002113477 * |
| RABINOVITCH, MARLENE: "Elastase and elastase inhibitors and pulmonary and coronary artery disease", INT. CONGR. SER. (1998), 1155(ATHEROSCLEROSIS XI), 317-326, XP002113474 * |
| RABINOVITCH, MARLENE: "Elastase and the pathobiology of unexplained pulmonary hypertension", CHEST (1998), 114(3, SUPPL., BRENOT MEMORIAL SYMPOSIUM ON THE PATHOGENESIS OF PRIMARY PULMONARY HYPERTENSION, 1997), 213S-224S, XP002113473 * |
| WEBSTER, J. ET AL: "Elastase-specific inhibitor elafin and endogenous vascular elastase (EVE) in vascular development.", FASEB JOURNAL, (1997) VOL. 11, NO. 3, PP. A224. MEETING INFO.: ANNUAL MEETING OF THE PROFESSIONAL RESEARCH SCIENTISTS ON EXPERIMENTAL BIOLOGY 97 NEW ORLEANS, LOUISIANA, USA APRIL 6-9, 1997, XP002113472 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999043308A2 (en) | 1999-09-02 |
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