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WO1997001344A3 - Method of dynamic retardation of cell cycle kinetics to potentiate cell damage - Google Patents

Method of dynamic retardation of cell cycle kinetics to potentiate cell damage Download PDF

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Publication number
WO1997001344A3
WO1997001344A3 PCT/US1996/010921 US9610921W WO9701344A3 WO 1997001344 A3 WO1997001344 A3 WO 1997001344A3 US 9610921 W US9610921 W US 9610921W WO 9701344 A3 WO9701344 A3 WO 9701344A3
Authority
WO
WIPO (PCT)
Prior art keywords
inhibitor
tci
agents
staurosporine
administering
Prior art date
Application number
PCT/US1996/010921
Other languages
French (fr)
Other versions
WO1997001344A2 (en
Inventor
Philip M Grimley
Sunil Mehta
Original Assignee
Jackson H M Found Military Med
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 Jackson H M Found Military Med filed Critical Jackson H M Found Military Med
Priority to JP9504545A priority Critical patent/JPH11509193A/en
Priority to CA002225682A priority patent/CA2225682A1/en
Priority to AU63960/96A priority patent/AU715527B2/en
Priority to EP96923453A priority patent/EP0835111A2/en
Publication of WO1997001344A2 publication Critical patent/WO1997001344A2/en
Publication of WO1997001344A3 publication Critical patent/WO1997001344A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (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)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Method for inducing cell damage by administering a restraining agent (RA) to a target cell population at a concentration and under conditions sufficient to retard but not arrest the progress of the target cells through the cell cycle, and administering a targeted cytotoxic insult (TCI) concomitant with or subsequent to the application of the RA. The invention also relates to a microculture indicator system and auxiliary data analysis procedures for identifying, designing and using new agents as restraining agents or targeted cytotoxic insults, and for improving synergistic combinations of existing agents. In embodiments of the invention, the RA can be a ribonucleotide reductase inhibitor, a dihydrofolate reductase inhibitor, a thymidylate synthase inhibitor, a DNA polymerase inhibitor, a protein kinase inhibitor or a topoisomerase inhibitor. In addition, embodiments of the invention include, as TCI, indole carbazoles, such as staurosporine, K252a, KT5926, and KT5720. In a specific embodiment, the RA is thymidine and the TCI is staurosporine.
PCT/US1996/010921 1995-06-27 1996-06-26 Method of dynamic retardation of cell cycle kinetics to potentiate cell damage WO1997001344A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP9504545A JPH11509193A (en) 1995-06-27 1996-06-26 A method for dynamically delaying cell cycle dynamics to enhance cell injury
CA002225682A CA2225682A1 (en) 1995-06-27 1996-06-26 Method of dynamic retardation of cell cycle kinetics to potentiate cell damage
AU63960/96A AU715527B2 (en) 1995-06-27 1996-06-26 Method of dynamic retardation of cell cycle kinetics to potentiate cell damage
EP96923453A EP0835111A2 (en) 1995-06-27 1996-06-26 Method of dynamic retardation of cell cycle kinetics to potentiate cell damage

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US54695P 1995-06-27 1995-06-27
US60/000,546 1995-06-27
US66893296A 1996-06-24 1996-06-24
US08/668,932 1996-06-24

Publications (2)

Publication Number Publication Date
WO1997001344A2 WO1997001344A2 (en) 1997-01-16
WO1997001344A3 true WO1997001344A3 (en) 1997-03-27

Family

ID=26667798

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/010921 WO1997001344A2 (en) 1995-06-27 1996-06-26 Method of dynamic retardation of cell cycle kinetics to potentiate cell damage

Country Status (5)

Country Link
EP (1) EP0835111A2 (en)
JP (1) JPH11509193A (en)
AU (1) AU715527B2 (en)
CA (1) CA2225682A1 (en)
WO (1) WO1997001344A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2669982A1 (en) * 2006-11-17 2008-05-29 Schering Corporation Combination therapy for proliferative disorders

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4448534A (en) * 1978-03-30 1984-05-15 American Hospital Corporation Antibiotic susceptibility testing
EP0359981A1 (en) * 1988-08-18 1990-03-28 Roche Diagnostics GmbH Pharmaceutical combinations and their use as antineoplastic medicines
WO1991007180A1 (en) * 1989-10-13 1991-05-30 City Of Hope Circumvention of human tumor drug resistance
WO1992019765A1 (en) * 1991-05-08 1992-11-12 The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services Method for designing cancer treatment regimens and methods and pharmaceutical compositions for the treatment of cancer
WO1993000909A1 (en) * 1991-07-03 1993-01-21 Regeneron Pharmaceuticals, Inc. Method and assay system for neurotrophin activity
WO1993009782A1 (en) * 1991-11-15 1993-05-27 Smithkline Beecham Corporation Combination chemotherapy
WO1994004541A2 (en) * 1992-08-12 1994-03-03 The Upjohn Company Protein kinase inhibitors and related compounds combined with taxol
WO1994018990A1 (en) * 1993-02-26 1994-09-01 Research Development Foundation Combination cisplatin/tamoxifen therapy for human cancers
WO1995000520A1 (en) * 1993-06-17 1995-01-05 Ciba-Geigy Ag Indolocarbazole compound useful as proteinkinase c inhibitor

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4448534A (en) * 1978-03-30 1984-05-15 American Hospital Corporation Antibiotic susceptibility testing
EP0359981A1 (en) * 1988-08-18 1990-03-28 Roche Diagnostics GmbH Pharmaceutical combinations and their use as antineoplastic medicines
WO1991007180A1 (en) * 1989-10-13 1991-05-30 City Of Hope Circumvention of human tumor drug resistance
WO1992019765A1 (en) * 1991-05-08 1992-11-12 The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services Method for designing cancer treatment regimens and methods and pharmaceutical compositions for the treatment of cancer
WO1993000909A1 (en) * 1991-07-03 1993-01-21 Regeneron Pharmaceuticals, Inc. Method and assay system for neurotrophin activity
WO1993009782A1 (en) * 1991-11-15 1993-05-27 Smithkline Beecham Corporation Combination chemotherapy
WO1994004541A2 (en) * 1992-08-12 1994-03-03 The Upjohn Company Protein kinase inhibitors and related compounds combined with taxol
WO1994018990A1 (en) * 1993-02-26 1994-09-01 Research Development Foundation Combination cisplatin/tamoxifen therapy for human cancers
WO1995000520A1 (en) * 1993-06-17 1995-01-05 Ciba-Geigy Ag Indolocarbazole compound useful as proteinkinase c inhibitor

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BENZ, C. ET AL: "Tamoxifen and 5-Fluorouracil in Breast Cancer: Cytotoxic Synergism", CANCER RESEARCH, vol. 43, 1983, pages 5298 - 5303, XP002017534 *
CAPIZZI, R.L. ET AL: "Combination Chemotherapy - Theory and Practice", SEMINARS IN ONCOLOGY, vol. 4, no. 2, 1977, pages 227 - 253, XP002017535 *
CHANG T.T. ET AL: "Synergistic effect of 4-hydroperoxycyclophosphamide and etopside on a human promyelocytic leukemia cell line (HL-60) demonstrated by computer analysis", CANCER RES. (UNITED STATES), vol. 45, no. 6, 1985, pages 2434 - 2439, XP002024374 *
CHOU T.-C. ET AL: "Quantitation of the synergistic interaction of edatrexate and cisplatin in vitro", CANCER CHEMOTHER. PHARMACOL. (GERMANY), vol. 31, no. 4, 1993, XP002024380 *
FRANKFURT,O.S.: "Combination Chemotherapy and DNA Repair Inhibition", ANTICANCER RESEARCH, vol. 12, no. 6A, 1992, pages 1795 - 1796, XP002018044 *
FROST P. ET AL: "Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells", CANCER RES. (UNITED STATES), vol. 50, no. 15, 1990, pages 4572 - 4577, XP002024373 *
GRANT, S. ET AL: "Modulation of 1-[beta-D-Arabinofuranosyl]Cytosine-Induced Apoptosis in Human Myeloid Leukemia Cells by Staurosporine and Other Pharmacological Inhibitors of Protein Kinase C", ONCOLOGY RESEARCH, vol. 6, no. 2, 1994, pages 87 - 99, XP002017533 *
HOFMANN, J. ET AL: "Enhancement of the Antiproliferative Effect of cis-Diamminechloroplatinum (II) and Nitrogen Mustard by Inhibitors of Proteine Kinase C", INT. J. CANCER, vol. 42, 1988, pages 382 - 388, XP002017532 *

Also Published As

Publication number Publication date
AU6396096A (en) 1997-01-30
EP0835111A2 (en) 1998-04-15
JPH11509193A (en) 1999-08-17
CA2225682A1 (en) 1997-01-16
AU715527B2 (en) 2000-02-03
WO1997001344A2 (en) 1997-01-16

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