WO1995018609A1 - Human leukocyte 12-lipoxygenase, mediation of its pathway, and consequences thereof - Google Patents

Human leukocyte 12-lipoxygenase, mediation of its pathway, and consequences thereof Download PDF

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Publication number
WO1995018609A1
WO1995018609A1 PCT/US1994/000089 US9400089W WO9518609A1 WO 1995018609 A1 WO1995018609 A1 WO 1995018609A1 US 9400089 W US9400089 W US 9400089W WO 9518609 A1 WO9518609 A1 WO 9518609A1
Authority
WO
WIPO (PCT)
Prior art keywords
pathway
aii
mediation
lipoxygenase
consequences
Prior art date
Application number
PCT/US1994/000089
Other languages
French (fr)
Inventor
Jerry L. Nadler
Rama Devi Natarajan
Original Assignee
City Of Hope
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
Application filed by City Of Hope filed Critical City Of Hope
Priority to AU70906/94A priority Critical patent/AU7090694A/en
Priority to EP94919966A priority patent/EP0696193A4/en
Publication of WO1995018609A1 publication Critical patent/WO1995018609A1/en
Priority to US08/945,744 priority patent/US6191169B1/en
Priority to US09/691,845 priority patent/US6486181B1/en
Priority to US09/739,843 priority patent/US6893829B2/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004Oxidoreductases (1.)
    • C12N9/0069Oxidoreductases (1.) acting on single donors with incorporation of molecular oxygen, i.e. oxygenases (1.13)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/155Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y113/00Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13)
    • C12Y113/11Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13) with incorporation of two atoms of oxygen (1.13.11)
    • C12Y113/11012Linoleate 13S-lipoxygenase (1.13.11.12)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y113/00Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13)
    • C12Y113/11Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13) with incorporation of two atoms of oxygen (1.13.11)
    • C12Y113/11031Arachidonate 12-lipoxygenase (1.13.11.31), i.e. lipoxygenase-type-12
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes

Abstract

The discovery and regulation of a 12-LO isoform (hl 12-LO) expressed in human tissues and of a similar isoform in PVSMCs is described. Various ribozyme and chemical inhibitors of the hl 12-LO pathway are described. The involvement of this 12-LO pathway in AII induced hypertrophy is demonstrated. It is shown that HG culture potentiates the stimulatory effects of AII and HETE in vascular smooth muscles. A specific aspect of the invention is the discovery that activation of a 12-LO pathway in vascular smooth muscle accentuates AII induced vascular hypertrophic response in diabetes mellitus. Human therapy involving mediation of the hl 12-LO pathway is described.
PCT/US1994/000089 1992-08-28 1994-01-04 Human leukocyte 12-lipoxygenase, mediation of its pathway, and consequences thereof WO1995018609A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU70906/94A AU7090694A (en) 1992-08-28 1994-01-04 Human leukocyte 12-lipoxygenase, mediation of its pathway, and consequences thereof
EP94919966A EP0696193A4 (en) 1992-08-28 1994-01-04 Human leukocyte 12-lipoxygenase, mediation of its pathway, and consequences thereof
US08/945,744 US6191169B1 (en) 1992-08-28 1996-05-03 Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states
US09/691,845 US6486181B1 (en) 1992-08-28 2000-10-18 Human leukocutye 12-lipoxygenase and its role in the pathogenesis of disease states
US09/739,843 US6893829B2 (en) 1992-08-28 2000-12-20 Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US93666092A 1992-08-28 1992-08-28

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US93666092A Continuation-In-Part 1992-08-28 1992-08-28

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US43468195A Continuation-In-Part 1992-08-28 1995-05-04
US09/739,843 Continuation-In-Part US6893829B2 (en) 1992-08-28 2000-12-20 Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states

Publications (1)

Publication Number Publication Date
WO1995018609A1 true WO1995018609A1 (en) 1995-07-13

Family

ID=25468927

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US1993/008106 WO1994005777A1 (en) 1992-08-28 1993-08-26 Inhibition of the formation or activity of human leukocyte 12-lipoxygenase pathway
PCT/US1994/000089 WO1995018609A1 (en) 1992-08-28 1994-01-04 Human leukocyte 12-lipoxygenase, mediation of its pathway, and consequences thereof

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/US1993/008106 WO1994005777A1 (en) 1992-08-28 1993-08-26 Inhibition of the formation or activity of human leukocyte 12-lipoxygenase pathway

Country Status (5)

Country Link
EP (2) EP0621895A4 (en)
JP (1) JPH07500254A (en)
AU (2) AU674339B2 (en)
CA (1) CA2077461C (en)
WO (2) WO1994005777A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996034943A1 (en) * 1995-05-04 1996-11-07 City Of Hope Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states
WO1999058979A1 (en) * 1998-05-13 1999-11-18 South Eastern Sydney Area Health Service A method of monitoring pancreatic tissue viability
US6103496A (en) * 1998-05-29 2000-08-15 Vanderbilt University Isolated and purified 12R-lipoxygenase protein and nucleic acids
US6893829B2 (en) 1992-08-28 2005-05-17 City Of Hope Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1171609B1 (en) 1999-04-12 2008-06-25 Lexicon Pharmaceuticals, Inc. Lipoxygenase proteins and polynucleotides encoding the same
CN1301847A (en) * 1999-12-27 2001-07-04 上海博德基因开发有限公司 New polypeptide-lipoxidase 10 and polynucleotide codign such polypeptide
CN1313389A (en) * 2000-03-15 2001-09-19 上海博德基因开发有限公司 Polypeptide-human lipoxidase 9 and polynucleotide for coding it

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4849445A (en) * 1983-12-14 1989-07-18 The Upjohn Company Method for treating or preventing deep vein thrombosis using lipoxygenase inhibitors
JPH0815851B2 (en) * 1987-10-09 1996-02-21 日産自動車株式会社 Differential limiting device

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Endocrinology, Vol. 134, No. 1, issued January 1994, J. GU et al., "Evidence that a Leukocyte Type of 12-Lipoxygenase is Expressed and Regulated by Angiotensin II in human Adrenal Glumerulosa Cells", pages 70-77, see Abstract. *
FASEB Journal, Vol. 6, issued 1992, J. GU et al., "Evidence for Expression of a New Form of 12-Lipoxygenase (12-LO) in Human Cells", page A1564, Abstract No. 3638, see entire Abstract. *
Proceedings of the National Academy of Sciences, USA, Vol. 87, issued March 1990, T. YOSHIMOTO et al., "Cloning and Sequence Analysis of the cDNA for Arachdonate 12-Lipoxygenase of Porcine Leukocytes", pages 2142-2146, see Abstract. *
Proceedings of the National Academy of Sciences, Vol. 90, issued June 1993, R. NATARANJAN et al., "Elevated Glucose and Angiotensin II Increase 12-Lipoxygenase Activity and Expression in Porcine Aortic Smooth Muscle Cells", pages 4947-4951, see Abstract and page 4951, cols. 1-2. *
Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 45, issued 1992, P.P.H. LEE et al., "Regulation of Proliferation of Rat Mammary Tumor Cells by Inhibitors of Cyclooxygenase and Lipoxygenase", pages 21-31, see Abstract. *
See also references of EP0696193A4 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6893829B2 (en) 1992-08-28 2005-05-17 City Of Hope Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states
WO1996034943A1 (en) * 1995-05-04 1996-11-07 City Of Hope Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states
WO1999058979A1 (en) * 1998-05-13 1999-11-18 South Eastern Sydney Area Health Service A method of monitoring pancreatic tissue viability
US6103496A (en) * 1998-05-29 2000-08-15 Vanderbilt University Isolated and purified 12R-lipoxygenase protein and nucleic acids
US6569644B2 (en) 1998-05-29 2003-05-27 Vanderbilt University Isolated and purified 12R-lipoxygenase protein and nucleic acids

Also Published As

Publication number Publication date
AU7090694A (en) 1995-08-01
CA2077461A1 (en) 1994-03-01
EP0696193A1 (en) 1996-02-14
WO1994005777A1 (en) 1994-03-17
EP0621895A1 (en) 1994-11-02
AU674339B2 (en) 1996-12-19
CA2077461C (en) 2000-02-15
EP0621895A4 (en) 1996-11-27
JPH07500254A (en) 1995-01-12
AU4840393A (en) 1994-03-29
EP0696193A4 (en) 1996-11-27

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