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WO1997005870A2 - Emploi de griseofulvine pour inhiber la croissance des cancers - Google Patents

Emploi de griseofulvine pour inhiber la croissance des cancers Download PDF

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Publication number
WO1997005870A2
WO1997005870A2 PCT/US1996/012475 US9612475W WO9705870A2 WO 1997005870 A2 WO1997005870 A2 WO 1997005870A2 US 9612475 W US9612475 W US 9612475W WO 9705870 A2 WO9705870 A2 WO 9705870A2
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WO
WIPO (PCT)
Prior art keywords
agents
griseofulvin
composition according
pharmaceutical composition
tumors
Prior art date
Application number
PCT/US1996/012475
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English (en)
Other versions
WO1997005870A3 (fr
Inventor
James Berger Camden
Original Assignee
The Procter & Gamble Company
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 to IL12309496A priority Critical patent/IL123094A0/xx
Priority to IL13301499A priority patent/IL133014A0/xx
Priority to SK142-98A priority patent/SK14298A3/sk
Priority to JP9508495A priority patent/JPH11511136A/ja
Priority to EP96926807A priority patent/EP0841914A2/fr
Priority to HU9903506A priority patent/HUP9903506A3/hu
Application filed by The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to MX9800945A priority patent/MX9800945A/es
Priority to BR9609920A priority patent/BR9609920A/pt
Priority to AU66834/96A priority patent/AU713031B2/en
Publication of WO1997005870A2 publication Critical patent/WO1997005870A2/fr
Publication of WO1997005870A3 publication Critical patent/WO1997005870A3/fr
Priority to NO980420A priority patent/NO980420L/no

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Classifications

    • 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
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • griseofulvin for inhibiting the growth of cancers
  • This invention is a pharmaceutical composition that is useful for the treatment of cancers and tumors, particularly in human and warm blooded animals.
  • the composition contains griseofulvin. It can be used in combination with other chemotherapeutic agents also.
  • the exact cause of leukemia is not known, but links between certain activities such as smoking or exposure to carcinogens and the incidence of certain types of leukemia and tumors has been shown by a number of researchers.
  • Many types of chemotherapeutic agents have been shown to be effective against cancers, tumors and leukemia, but not all types of cancer and tumor cells respond to these agents. Unfortunately, many of these agents also destroy normal cells. The exact mechanism for the action of these chemotherapeutic agents are not always known.
  • cytocidal or cytostatic agents work best on cancers with large growth factors, i.e., ones whose cells are rapidly dividing.
  • hormones in particular estrogen, progesterone and testosterone, and some antibiotics produced by a variety of microbes, alkylating agents, and anti-metabolites form the bulk of therapies available to oncologists.
  • cytotoxic agents that have specificity for leukemia, cancer and tumor cells while not affecting normal cells would be extremely desirable. Unfortunately, none have been found and instead agents which target especially rapidly dividing cells (both diseased and normal) have been used.
  • i' is an object of this invention to provide a pharmaceutical composition that is effective in treating leukemia with mild or no effects on normal blood cells
  • a composition comprising a pharmaceutical carrier and a griseofulvin as defined herein along with a method for treating cancer, leukemia and tumors.
  • griseofulvin in combination with other chemotherapeutic agents which are effective in destroying the tumor is a novel method of treatment.
  • Griseofulvin can also be used to treat viral infections in the presence of a potentiator.
  • a pharmaceutical composition for treatment of mammals, and in particular, warm blooded animals and humans, which are affected by leukemia comprising a pharmaceutical carrier and an effective amount of griseofulvin.
  • Griseofulvin has the formula:
  • compositions can be used to inhibit the growth of leukemia, tumors and cancer cells in humans or animals by administration of an effective amount either orally, rectally, topically or parenterally, or intravenously. These compositions do not significantly affect healthy cells.
  • Potentiators can also be used in combination with griseofulvin as can chemotherapeutic agents.
  • the term “comprising” means various components can be conjointly employed in the pharmaceutical composition of this invention. Accordingly, the terms “consisting essentially o and “consisting o are embodied in the term comprising.
  • a "pharmaceutically acceptable” component is one that is suitable for use with humans and or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio.
  • safe and effective amount refers to the quantity of a component which is sufficient to yield a desired therapeutic response without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit/risk ratio when used in the manner of this invention.
  • the specific "safe and effective amount” will, obviously, vary with such factors as the particular condition being treated, the physical condition of the patient, the type of mammal being treated, the duration of the treatment, the nature of concurrent therapy (if any), and the specific formulations employed and the structure of the compounds or its derivatives.
  • a "pharmaceutical addition salts” is salt of the anti-leukemia compound with an organic or inorganic acid.
  • These preferred acid addition salts are chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formates, tartrates, maleates, malates, citrates, benzoates, salicylates, ascorbates, and the like.
  • a “pharmaceutical carrier” is a pharmaceutically acceptable solvent, suspending agent or vehicle for delivering the anti-leukemia agent to the animal or human.
  • the carrier may be liquid or solid and is selected with the planned manner of administration in mind.
  • cancer or “leukemia” refers to all types of cancers or neoplasm or malignant disease which attack normal healthy blood cells or bone marrow which produces blood cells which are found in mammals.
  • virus includes viruses which cause diseases in warm blooded animals including HIV, influenza, rhinoviruses, herpes and the like.
  • grisofulvin means 7-Chloro-2',4,6-trimethoxy-6-methylspiro
  • potentiators are materials such as triprolidine and its cis-isomer which are used in combination with griseofulvin. Potentiators can suppress the immune system or enhance the effectiveness of the drugs.
  • chemotherapeutic agents includes DNA-interactive Agents, Antime- tabolites, Tubulin-Interactive Agents, Hormonal agents and others, such as Asparaginase or hydroxyurea.
  • GRISEOFULVIN Griseofulvin has the following structure:
  • the chemotherapeutic agents are generally grouped as DNA-interactive Agents, Antimetabolites, Tubulin-Interactive Agents, Hormonal agents and others such as Asparaginase or hydroxyurea. Each of the groups of chemotherapeutic agents can be further divided by type of activity or compound.
  • the chemotherapeutic agents used in combination with griseofulvin include members of all of these groups.
  • DNA-interactive Agents include the alkylating agents, e.g. Cisplatin, Cyclophosphamide, Altretamine; the DNA strand-breakage agents, such as Bleomycin; the intercalating topoisomerase II inhibitors, e.g., Dactinomycin and Doxorubicin); the nonintercalating topoisomerase II inhibitors such as, Etoposide and Teniposde; and the DNA minor groove binder
  • the alkylating agents form covalent chemical adducts with cellular DNA, RNA, and protein molecules and with smaller amino acids, glutathione and similar chemicals. Generally, these alkylating agents react with a nucleophilic atom in a cellular constituent, such as an amino, carboxyl, phosphate, sulfhydryl group in nucleic acids, proteins, amino acids, or glutathione. The mechanism and the role of these alkylating agents in cancer therapy is not well understood.
  • Typical alkylating agents include: Nitrogen mustards, such as Chlorambucil, Cyclophosphamide, Isofamide,
  • Mechlorethamine, Melphalan, Uracil mustard such as Thiotepa methanesulphonate esters such as Busulfan; nitroso ureas, such as Carmustine, Lomustine, Streptozocin; platinum complexes, such as Cisplatin, Carboplatin; bioreductive alkylator, such as Mitomycin, and Procarbazine, dacarbazine and Altretamine;
  • DNA strand breaking agents include Bleomycin; DNA topoisomerase II inhibitors include the following: Intercalators, such as Amsacrine, Dactinomycin, Daunorubicin, Doxorubicin,
  • the DNA minor groove binder is Plicamycin.
  • the antimetabolites interfere with the production of nucleic acids by one or the other of two major mechanisms. Some of the drugs inhibit production of the deoxyribonucleoside triphosphates that are the immediate precursors for DNA synthesis, thus inhibiting DNA replication. Some of the compounds are sufficiently like purines or pyrimidines to be able to substitute for them in the anabolic nucleotide pathways. These analogs can then be substituted into the DNA and RNA instead of their normal counterparts.
  • the antimetabolites useful herein include: folate antagonists such as Methotrexate and trimetrexate pyrimidine antagonists, such as Fluorouracil, Fluorodeoxyuridine, CB3717, Azacitidine,
  • Cytarabine, and Floxuridine purine antagonists include Mercaptopurine, 6-Thioguanine, Fludarabine, Pentostatin; sugar modified analogs include Cyctrabine, Fludarabine; ribonucleotide reductase inhibitors include hydroxyurea.
  • Tubulin Interactive agents act by binding to specific sites on tubulin, a protein that polymerizes to form cellular microtubules. Microtubules are critical cell structure units. When the interactive agents bind on the protein, the cell can not form microtubules
  • Tubulin Interactive agents include Vincristine and Vinblasune, both alkaloids and Paclitaxel.
  • Hormonal agents are also useful in the treatment of cancers and tumors. They are used in hormonally susceptible tumors and are usually derived from natural sources. These include: estrogens, conjugated estrogens and Ethinyl Estradiol and Diethylsulbesterol, Chlortrianisen and Idenestrol; progestins such as Hydroxyprogesterone caproate, Medroxyprogesterone, and Megestrol; androgens such as testosterone, testosterone propionate; fluoxymesterone, methyltestosterone;
  • Adrenal corticosteroids are derived from natural adrenal cortisol or hydrocortisone. They are used because of their anti inflammatory benefits as well as the ability of some to inhibit mitotic divisions and to halt DNA synthesis. These compounds include, Prednisone, Dexamethasone, Methylprednisolone, and Prednisolone. Leutinizing hormone releasing hormone agents or gonadotropin-releasing hormone antagonists are used primarily the treatment of prostate cancer. These include leuprolide acetate and goserelin acetate. They prevent the biosynthesis of steroids in the testes.
  • Antihormonal antigens include: antiestrogenic agents such as Tamosifen, antiandrogen agents such as Flutamide ; and antiadrenal agents such as Mitotane and Aminoglutethimide.
  • Hydroxyurea appears to act primarily through inhibition of the enzyme ribonucleotide reductase.
  • Asparaginase is an enzyme which converts asparagine to nonfunctional aspartic acid and thus blocks protein synthesis in the tumor.
  • D. POTENTIATORS are enzymes which converts asparagine to nonfunctional aspartic acid and thus blocks protein synthesis in the tumor.
  • potentiators can be any material which improves or increase the efficacy of the pharmaceutical composition or acts as an immunosuppressor.
  • One such potentiator is triprolidine and its cis-isomer which are used in combination with the chemotherapeutic agents and the griseofulvin.
  • Triprolidine is described in US 5,114,951 (1992).
  • Another potentiator is procodazole, lH-Benzimidazole-2-propanoic acid; [ ⁇ -(2-benzimidazole) propionic acid; 2-(2- carboxyethyl)benzimidazole; propazol].
  • Procodazole is a non-specific active immunoprotective agent against viral and bacterial infections and can be used with the compositions claimed herein. It is effective with griseofulvin alone in treating cancers, tumors, leukemia and viral infections or combined with chemotherapeutic agents.
  • Propionic acid and its salts and esters can also be used in combination with the pharmaceutical compositions claimed herein.
  • Antioxidant vitamins such as vitamins A, C and E and beta-carotene can be added to these compositions.
  • any suitable dosage may be given in the method ofthe invention.
  • the type of compound and the carrier and the amount will vary widely depending on the species of the warm blooded animal or human, body weight, and the type of cancer or tumor or viral infection being treated.
  • a dosage of between about 1 milligram (mg) per kilogram (kg) of body weight and about 8000 mg per kg of body weight is suitable for either the griseofulvin or the chemotherapeutic agent.
  • Preferably from 15 mg to about 5000 mg/kg of body weight is used.
  • the dosage in man is lower than for small warm blooded mammals such as mice.
  • a dosage unit may comprise a single compound or mixtures thereof with other compounds or other cancer inhibiting compounds.
  • the dosage unit can also comprise diluents, extenders, carriers, liposomes and the » like.
  • the unit may be in solid or gel form such as pills, tablets, capsules and the like or in liquid form suitable for oral, rectal, topical, intravenous injection or parenteral administration or injection into or around the bone marrow.
  • the range and ratio of griseofulvin to chemotherapeutic agent will depend on the type of cancer or tumor being treated and the particular chemotherapeutic agent.
  • the chemotherapeutic agents, griseofulvin and, optionally, the potentiators are typically mixed with a pharmaceutically acceptable carrier.
  • This carrier can be a solid or liquid and the type is generally chosen based on the type of administration being used.
  • the active agent can be coadministered in the form of a tablet or capsule, liposome, as an agglomerated powder or in a liquid form.
  • suitable solid carriers include lactose, sucrose, gelatin and agar. Capsule or tablets can be easily formulated and can be made easy to swallow or chew; other solid forms include granules, and bulk powders.
  • Tablets may contain suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, and melting agents.
  • suitable liquid dosage forms include solutions or suspensions in water, pharmaceutically acceptable fats and oils, alcohols or other organic solvents, including esters, emulsions, syrups or elixirs, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules.
  • Such liquid dosage forms may contain, for example, suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, thickeners, and melting agents.
  • Oral dosage forms optionally contain flavorants and coloring agents.
  • Parenteral and intravenous forms would also include minerals and other materials to make them compatible with the type of injection or delivery system chosen.
  • the method of treatment can be any suitable method which is effective in the treatment of the particular cancer or tumor type being treated.
  • Treatment may be oral, rectal, topical, parenteral or intravenous administration or by injection into the tumor or cancer.
  • the method of applying an effective amount also varies depending on the leukemia, cancer, tumor or virus being treated. It is believed that parenteral treatment by intravenous, subcutaneous, or intramuscular application ofthe griseofulvin, formulated with an appropriate carrier, additional cancer inhibiting compound or compounds or diluent to facilitate application will be the preferred method of administering the compounds to warm blooded animals.
  • griseofulvin can be combined with fungicides, herbicides or other antiviral agents.
  • Preferred herbicides and fungicides include carbendazim, fluoconazole, benomyl, glyphosate and propicodazole.
  • griseofulvin inhibited viral replication by 98% at lO ⁇ g ml with a therapeutic index of 5.3.
  • AZT a known HIV drug
  • the therapeutic index is the ratio of toxic dose of drug to efficacious dose of drug.
  • griseofulvin showed an increase in the survival time relative to a non treated control of 156% at 4000 mg/kg dose; 188% at 5000 mg/kg dose; and 218% at 6000 mg/kg dose.
  • griseofulvin showed an increase in the survival time relative to a nontreated control of 165% at 4000 mg/kg dose; 179% at 5000 mg/kg dose; and 201% at 6000 mg/kg dose. Cytoxan at 300 mg/kg showed an increased survival rate of 192%.
  • Rhinovirus type A-l, cell line WI-38
  • griseofulvin was effective at 100 ⁇ g/ml.
  • the positive control was A-36683 of Abbot Company, (S,S)-l,2-bis(5- methoxy-2-benzimidazolyl)-l,2-ethanediol.
  • A-36683 has a therapeutic index of 1000-3200.
  • Griseofulvin has a therapeutic index of 1-2. (See Schleicher et al, Applied Microbiology, 23, No. 1, 113-116 (1972).
  • Solid tumors removed by patients are minced into 2 to 5 mm fragments and immediately placed in McCoy's Medium 5A plus 10% heat inactivated newborn calf serum plus 1% penicillin streptomycin. Within 4 hours, these solid tumors are mechanically disassociated with scissors, forced through No. 100 stainless steel mesh, through 25 gauge needles, and then washed with McCoy's medium as described above. Ascitic, pleural, pericardial fluids and bone marrow are obtained by standard techniques. The fluid or marrow is placed in sterile containers containing 10 units of preservative free heparin per ml. of malignant fluid or marrow. After centrifugation at 150 x g for 10 minutes, the cells are harvested and washed with McCoy's medium plus 10% heat inactivated calf serum. The viability of cell suspensions is determined on a hemocytometer with trypan blue.
  • Cells to be cloned are suspended in 0.3% agar in enriched CMRL1066 supplemented with 15% heat inactivated horse serum, penicillin (100 units/ml), streptomycin (2mg ml), glutamine (2mM), insulin (3 units/ml), asparagine (0.6 mg/ml), and HEPES buffer (2mM).
  • penicillin 100 units/ml
  • streptomycin 2mg ml
  • insulin 3 units/ml
  • asparagine 0.6 mg/ml
  • HEPES buffer HEPES buffer
  • the number of colonies (defined as 50 cells) formed in the 3 compound treated plates is compared to the number of colonies formed in the 3 control plates, and the percent colonies surviving at the concentration of compound can be estimated.
  • Three positive control plates are used to determine survival rate. Orthosodium vanadate at 200 ⁇ g/ml is used as the positive control. If there is ⁇ 30% colonies in the positive control when compared to the untreated control, the test is evaluated.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Furan Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne une composition pharmaceutique pour le traitement de cancers ou de tumeurs chez les mammifères. Cette composition contient de la griséofulvine. On peut utiliser un agent chimiothérapeutique en association avec la griséofulvine, de même que des agents de potentialisation. La griséofulvine peut également être utilisée pour traiter des infections virales, seule, en association avec d'autres agents antiviraux ou avec un agent de potentialisation.
PCT/US1996/012475 1995-08-03 1996-07-30 Emploi de griseofulvine pour inhiber la croissance des cancers WO1997005870A2 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
IL13301499A IL133014A0 (en) 1995-08-03 1996-07-30 Pharmaceutical compositions containing griseofulvin for treating viral infections
SK142-98A SK14298A3 (en) 1995-08-03 1996-07-30 Use of griseofulvin for inhibiting the growth of cancers
JP9508495A JPH11511136A (ja) 1995-08-03 1996-07-30 癌の成長を阻害するためのグリセオフルビンの使用
EP96926807A EP0841914A2 (fr) 1995-08-03 1996-07-30 Emploi de griseofulvine pour inhiber la croissance des cancers
HU9903506A HUP9903506A3 (en) 1995-08-03 1996-07-30 Use of griseofulvin for inhibiting the growth of cancers
IL12309496A IL123094A0 (en) 1995-08-03 1996-07-30 Pharmaceutical compositions containing griseofulvin for inhibiting the growth of cancers
MX9800945A MX9800945A (es) 1995-08-03 1996-07-30 Uso de griseofulvina para inhibir el crecimiento de canceres.
BR9609920A BR9609920A (pt) 1995-08-03 1996-07-30 Uso de griseofulvina para inibir o crescimento de cânceres
AU66834/96A AU713031B2 (en) 1995-08-03 1996-07-30 Use of griseofulvin for inhibiting the growth of cancers
NO980420A NO980420L (no) 1995-08-03 1998-01-30 Anvendelse av griseofulvin for å inhibere cancervekst

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US183995P 1995-08-03 1995-08-03
US67418196A 1996-07-16 1996-07-16
US08/674,181 1996-07-16
US60/001,839 1996-07-16

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WO1997005870A2 true WO1997005870A2 (fr) 1997-02-20
WO1997005870A3 WO1997005870A3 (fr) 1997-04-17

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PCT/US1996/012475 WO1997005870A2 (fr) 1995-08-03 1996-07-30 Emploi de griseofulvine pour inhiber la croissance des cancers

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EP (1) EP0841914A2 (fr)
JP (1) JPH11511136A (fr)
KR (1) KR19990036137A (fr)
AR (1) AR003176A1 (fr)
AU (1) AU713031B2 (fr)
BR (1) BR9609920A (fr)
CA (1) CA2228503A1 (fr)
CZ (1) CZ30598A3 (fr)
HU (1) HUP9903506A3 (fr)
IL (1) IL123094A0 (fr)
MX (1) MX9800945A (fr)
NO (1) NO980420L (fr)
PL (1) PL324905A1 (fr)
SK (1) SK14298A3 (fr)
TR (1) TR199800244T2 (fr)
WO (1) WO1997005870A2 (fr)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6228876B1 (en) 1995-06-07 2001-05-08 The Procter & Gamble Company Pharmaceutical composition for inhibiting the growth of cancers
US6245789B1 (en) 1998-05-19 2001-06-12 The Procter & Gamble Company HIV and viral treatment
US6262093B1 (en) 1995-04-12 2001-07-17 The Proctor & Gamble Company Methods of treating cancer with benzimidazoles
US6265427B1 (en) 1995-06-07 2001-07-24 The Proctor & Gamble Company Pharmaceutical composition for the method of treating leukemia
US6329355B1 (en) 1997-01-28 2001-12-11 The Procter & Gamble Company Method for inhibiting the growth of cancers
US6380232B1 (en) 2000-09-26 2002-04-30 The Procter & Gamble Company Benzimidazole urea derivatives, and pharmaceutical compositions and unit dosages thereof
US6407105B1 (en) 2000-09-26 2002-06-18 The Procter & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
US6407131B1 (en) 1997-05-16 2002-06-18 The Procter & Gamble Company Compounds and method for use thereof in the treatment of cancer or viral infections
US6423734B1 (en) 1999-08-13 2002-07-23 The Procter & Gamble Company Method of preventing cancer
JP2002529426A (ja) * 1998-11-09 2002-09-10 アイデック・ファーマシューティカルズ・コーポレイション キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
US6462062B1 (en) 2000-09-26 2002-10-08 The Procter & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
US6479526B1 (en) 1995-04-12 2002-11-12 The Procter & Gamble Company Pharmaceutical composition for inhibiting the growth of viruses and cancers
US6498188B1 (en) 1995-04-12 2002-12-24 The Procter & Gamble Company Methods of treatment for cancer or viral infections
WO2003000290A1 (fr) * 2001-06-25 2003-01-03 Ajinomoto Co., Inc. Agents antitumoraux
US6608096B1 (en) 2000-09-26 2003-08-19 University Of Arizona Foundation Compounds and methods for use thereof in the treatment of cancer or viral infections
US6686391B2 (en) 1995-08-04 2004-02-03 University Of Arizona Foundation N-chlorophenylcarbamate and N-chlorophenylthiocarbamate compositions
EP2008652A1 (fr) * 2007-06-28 2008-12-31 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Analogues de la griséofulvine pour le traitement du cancer par inhibition du regroupement centrosomal
US7635722B1 (en) * 1998-07-27 2009-12-22 Saint Jude Pharmaceuticals, Inc. Chemical induced intracellular hyperthermia
WO2010072770A2 (fr) 2008-12-22 2010-07-01 Dkfz Deutsches Krebsforschungszentrum Analogues de griséofulvine pour le traitement du cancer par inhibition de l'agrégat centrosomial

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
THERAPIE, vol. 22, no. 5, 1967, pages 1143-1151, XP000617126 E. HUANT: "Premières expérimentations cliniques de l'activité anti-mitotique de la griséofulvine en thérapeutique antitumorale." *

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6479526B1 (en) 1995-04-12 2002-11-12 The Procter & Gamble Company Pharmaceutical composition for inhibiting the growth of viruses and cancers
US6262093B1 (en) 1995-04-12 2001-07-17 The Proctor & Gamble Company Methods of treating cancer with benzimidazoles
US6362207B1 (en) 1995-04-12 2002-03-26 The Procter & Gamble Company Methods of treating viral infections with benzimidazoles
US6498188B1 (en) 1995-04-12 2002-12-24 The Procter & Gamble Company Methods of treatment for cancer or viral infections
US6265427B1 (en) 1995-06-07 2001-07-24 The Proctor & Gamble Company Pharmaceutical composition for the method of treating leukemia
US6552059B2 (en) 1995-06-07 2003-04-22 University Of Arizona Foundation Pharmaceutical composition for and method of treating leukemia
US6228876B1 (en) 1995-06-07 2001-05-08 The Procter & Gamble Company Pharmaceutical composition for inhibiting the growth of cancers
US6686391B2 (en) 1995-08-04 2004-02-03 University Of Arizona Foundation N-chlorophenylcarbamate and N-chlorophenylthiocarbamate compositions
US6329355B1 (en) 1997-01-28 2001-12-11 The Procter & Gamble Company Method for inhibiting the growth of cancers
US6506783B1 (en) 1997-05-16 2003-01-14 The Procter & Gamble Company Cancer treatments and pharmaceutical compositions therefor
US6900235B1 (en) 1997-05-16 2005-05-31 Uaf Technologies And Research, Llc Benzimidazole compounds, and pharmaceutical compositions and unit dosages thereof
US6423736B1 (en) 1997-05-16 2002-07-23 The Proctor & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
US6864275B1 (en) 1997-05-16 2005-03-08 Uaf Technologies And Research, Llc Compounds and methods for use thereof in the treatment of cancer
US6710065B1 (en) 1997-05-16 2004-03-23 Uaf Technologies And Research, Llc Compounds and methods for use thereof in the treatment of cancer
US6420411B1 (en) 1997-05-16 2002-07-16 The Procter & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
US6482843B1 (en) 1997-05-16 2002-11-19 The Procter & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
US6407131B1 (en) 1997-05-16 2002-06-18 The Procter & Gamble Company Compounds and method for use thereof in the treatment of cancer or viral infections
US6245789B1 (en) 1998-05-19 2001-06-12 The Procter & Gamble Company HIV and viral treatment
US7635722B1 (en) * 1998-07-27 2009-12-22 Saint Jude Pharmaceuticals, Inc. Chemical induced intracellular hyperthermia
JP2010285439A (ja) * 1998-11-09 2010-12-24 Biogen Idec Inc キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
JP4842435B2 (ja) * 1998-11-09 2011-12-21 バイオジェン・アイデック・インコーポレイテッド キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
US8206711B2 (en) 1998-11-09 2012-06-26 Biogen Idec Inc. Treatment of chronic lymphocytic leukemia using anti-CD20 antibodies
JP2002529426A (ja) * 1998-11-09 2002-09-10 アイデック・ファーマシューティカルズ・コーポレイション キメラ抗ｃｄ２０抗体を用いた、循環腫瘍細胞に関連した血液学的悪性疾患の治療
US6423734B1 (en) 1999-08-13 2002-07-23 The Procter & Gamble Company Method of preventing cancer
US6906091B2 (en) 1999-08-13 2005-06-14 Uaf Technologies And Research, Llc Method of cancer treatment
US6608096B1 (en) 2000-09-26 2003-08-19 University Of Arizona Foundation Compounds and methods for use thereof in the treatment of cancer or viral infections
US6720349B2 (en) 2000-09-26 2004-04-13 Uaf Technologies And Research, Llc Compounds for use in the treatment of cancer or viral infections
US6916836B2 (en) 2000-09-26 2005-07-12 Uaf Technologies And Research, Llc Compounds and methods for use thereof in the treatment of viral infections
US6462062B1 (en) 2000-09-26 2002-10-08 The Procter & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
US6380232B1 (en) 2000-09-26 2002-04-30 The Procter & Gamble Company Benzimidazole urea derivatives, and pharmaceutical compositions and unit dosages thereof
US6407105B1 (en) 2000-09-26 2002-06-18 The Procter & Gamble Company Compounds and methods for use thereof in the treatment of cancer or viral infections
WO2003000290A1 (fr) * 2001-06-25 2003-01-03 Ajinomoto Co., Inc. Agents antitumoraux
WO2009000937A1 (fr) * 2007-06-28 2008-12-31 Dkfz Deutsches Krebsforschungszentrum Analogues de la griséofulvine pour le traitement du cancer par inhibition de l'agrégation centrosomale
EP2008652A1 (fr) * 2007-06-28 2008-12-31 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Analogues de la griséofulvine pour le traitement du cancer par inhibition du regroupement centrosomal
EP2204367A1 (fr) 2008-12-22 2010-07-07 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Analogues de la griséofulvine pour le traitement du cancer par inhibition du regroupement centrosomal
WO2010072770A2 (fr) 2008-12-22 2010-07-01 Dkfz Deutsches Krebsforschungszentrum Analogues de griséofulvine pour le traitement du cancer par inhibition de l'agrégat centrosomial
US20120035200A1 (en) * 2008-12-22 2012-02-09 Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts Griseofulvin analogues for the treatment of cancer by inhibition of centrosomal clustering
US9108941B2 (en) * 2008-12-22 2015-08-18 Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts Griseofulvin analogues for the treatment of cancer by inhibition of centrosomal clustering

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AU6683496A (en) 1997-03-05
NO980420L (no) 1998-04-03
AR003176A1 (es) 1998-07-08
CZ30598A3 (cs) 1998-06-17
WO1997005870A3 (fr) 1997-04-17
HUP9903506A3 (en) 2000-07-28
IL123094A0 (en) 1998-09-24
HUP9903506A2 (hu) 2000-06-28
BR9609920A (pt) 1999-07-06
TR199800244T2 (xx) 1998-09-21
NO980420D0 (no) 1998-01-30
MX9800945A (es) 1998-04-30
SK14298A3 (en) 1998-09-09
EP0841914A2 (fr) 1998-05-20
PL324905A1 (en) 1998-06-22
CA2228503A1 (fr) 1997-02-20
KR19990036137A (ko) 1999-05-25
JPH11511136A (ja) 1999-09-28
AU713031B2 (en) 1999-11-18

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