WO2001000193A3 - Zinc ionophores as anti-apoptotic agents - Google Patents

Zinc ionophores as anti-apoptotic agents Download PDF

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Publication number
WO2001000193A3
WO2001000193A3 PCT/IB2000/001005 IB0001005W WO0100193A3 WO 2001000193 A3 WO2001000193 A3 WO 2001000193A3 IB 0001005 W IB0001005 W IB 0001005W WO 0100193 A3 WO0100193 A3 WO 0100193A3
Authority
WO
WIPO (PCT)
Prior art keywords
zinc
apoptotic agents
zinc ionophores
ionophores
apoptosis
Prior art date
Application number
PCT/IB2000/001005
Other languages
French (fr)
Other versions
WO2001000193A2 (en
Inventor
Henry Fliss
Original Assignee
Zinc Therapeutics Canada Inc
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 Zinc Therapeutics Canada Inc filed Critical Zinc Therapeutics Canada Inc
Priority to JP2001505903A priority Critical patent/JP2003503346A/en
Priority to AU18396/01A priority patent/AU1839601A/en
Priority to CA002375852A priority patent/CA2375852A1/en
Priority to EP00979231A priority patent/EP1189604A2/en
Publication of WO2001000193A2 publication Critical patent/WO2001000193A2/en
Publication of WO2001000193A3 publication Critical patent/WO2001000193A3/en

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    • 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
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • 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
    • A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/315—Zinc compounds
    • 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
    • A61K31/325—Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic 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
    • A61K31/352—Heterocyclic 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 condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • 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
    • 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
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The present invention provides methods and compositions comprising one or more zinc ionophores for blocking apoptosis in patients in need thereof. Concentrations of zinc-pyrithione and diethyl-dithiocarbamate in the picomolar to nanomolar range have a strong protective effect against apoptosis.
PCT/IB2000/001005 1999-06-23 2000-06-23 Zinc ionophores as anti-apoptotic agents WO2001000193A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2001505903A JP2003503346A (en) 1999-06-23 2000-06-23 Zinc ionophore as an anti-apoptotic agent
AU18396/01A AU1839601A (en) 1999-06-23 2000-06-23 Zinc ionophores as anti-apoptotic agents
CA002375852A CA2375852A1 (en) 1999-06-23 2000-06-23 Zinc ionophores as anti-apoptotic agents
EP00979231A EP1189604A2 (en) 1999-06-23 2000-06-23 Zinc ionophores as anti-apoptotic agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14063299P 1999-06-23 1999-06-23
US60/140,632 1999-06-23

Publications (2)

Publication Number Publication Date
WO2001000193A2 WO2001000193A2 (en) 2001-01-04
WO2001000193A3 true WO2001000193A3 (en) 2001-12-06

Family

ID=22492127

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2000/001005 WO2001000193A2 (en) 1999-06-23 2000-06-23 Zinc ionophores as anti-apoptotic agents

Country Status (5)

Country Link
EP (1) EP1189604A2 (en)
JP (1) JP2003503346A (en)
AU (1) AU1839601A (en)
CA (1) CA2375852A1 (en)
WO (1) WO2001000193A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002080943A1 (en) * 2001-04-04 2002-10-17 Henry Fliss Zinc ionophores as anti-stress agents
WO2002089919A2 (en) * 2001-05-08 2002-11-14 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw Usage of zinc for preventing tnf-induced pathology during cancer therapy
EP2228045B1 (en) * 2003-01-15 2015-03-04 Stryker Corporation Ambulance cot loading and unloading device
JP2006206538A (en) * 2005-01-31 2006-08-10 Institute Of Physical & Chemical Research Functional controlling agent for antigen presenting cell
US10369108B2 (en) 2013-03-15 2019-08-06 Mylan Laboratories, Inc. Hot melt granulation formulations of poorly water-soluble active agents
AU2018260927B1 (en) * 2018-05-25 2019-02-21 Graham Sherard Baldwin Methods and compositions for inhibiting a noxious insult
JP7311086B2 (en) * 2019-08-21 2023-07-19 ブレイン ケミストリー ラブズ Compositions containing metals and L-serine, and uses thereof

Non-Patent Citations (20)

* Cited by examiner, † Cited by third party
Title
BIOCHEMICAL JOURNAL, vol. 296, no. 2, 1993, pages 403 - 408, ISSN: 0264-6021 *
BIOCHEMICAL PHARMACOLOGY, vol. 50, no. 7, 1995, pages 1021 - 1029, ISSN: 0006-2952 *
BIOCHEMISTRY INTERNATIONAL, vol. 24, no. 6, 1991, pages 1093 - 1102, ISSN: 0158-5231 *
BRAIN RESEARCH, vol. 743, no. 1-2, 1996, pages 362 - 365, ISSN: 0006-8993 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1 May 1999 (1999-05-01), CARMODY RUAIDHRI J ET AL: "Reactive oxygen species as mediators of photoreceptor apoptosis in vitro.", XP002165008, Database accession no. PREV199900285409 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1991, ZALEWSKI P D ET AL: "PHYSIOLOGICAL ROLE FOR ZINC IN PREVENTION OF APOPTOSIS GENE-DIRECTED DEATH", XP002165006, Database accession no. PREV199293030435 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1993, ZALEWSKI PETER D ET AL: "Correlation of apoptosis with change in intracellular labile Zn(II) using Zinquin ((2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetic acid), a new specific fluorescent probe for Zn(II).", XP002165005, Database accession no. PREV199497071032 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1994, TREVES SUSAN ET AL: "Apoptosis is dependent on intracellular zinc and independent of intracellular calcium in lymphocytes.", XP002165004, Database accession no. PREV199497270268 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1995, VERHAEGEN STEVEN ET AL: "Inhibition of apoptosis by antioxidants in the human HL-60 leukemia cell line.", XP002165013, Database accession no. PREV199598551157 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996, MATHIEU JACQUES ET AL: "Radiation-induced apoptosis in thymocytes: Inhibition by diethyldithiocarbamate and zinc.", XP002165009, Database accession no. PREV199799341723 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996, MATSUSHITA KOHJI ET AL: "Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus.", XP002165007, Database accession no. PREV199799382655 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; January 1998 (1998-01-01), TAGAMI M ET AL: "Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.", XP002165012, Database accession no. PREV199800147037 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; May 1999 (1999-05-01), TAGAMI MOTOKI ET AL: "Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.", XP002165010, Database accession no. PREV199900294771 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; November 1998 (1998-11-01), TAGAMI MOTOKI ET AL: "Vitamin E prevents apoptosis in cortical neurons during hypoxia and oxygen reperfusion.", XP002165011, Database accession no. PREV199900046515 *
EXPERIMENTAL CELL RESEARCH, vol. 211, no. 2, 1994, pages 339 - 343, ISSN: 0014-4827 *
EXPERIMENTAL CELL RESEARCH, vol. 248, no. 2, 1 May 1999 (1999-05-01), pages 520 - 530, ISSN: 0014-4827 *
LABORATORY INVESTIGATION, vol. 78, no. 11, November 1998 (1998-11-01), pages 1415 - 1429, ISSN: 0023-6837 *
LABORATORY INVESTIGATION, vol. 79, no. 5, May 1999 (1999-05-01), pages 609 - 615, ISSN: 0023-6837 *
RADIATION RESEARCH, vol. 146, no. 6, 1996, pages 652 - 659, ISSN: 0033-7587 *
STROKE, vol. 29, no. 1, January 1998 (1998-01-01), 23rd International Joint Conference on Stroke and Cerebral Circulation;Orlando, Florida, USA; February 5-7, 1998, pages 279, ISSN: 0039-2499 *

Also Published As

Publication number Publication date
CA2375852A1 (en) 2001-01-04
EP1189604A2 (en) 2002-03-27
AU1839601A (en) 2001-01-31
WO2001000193A2 (en) 2001-01-04
JP2003503346A (en) 2003-01-28

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