WO2004111262A1 - Procede d'identification d'un agent chimiotherapeutique selectif - Google Patents

Procede d'identification d'un agent chimiotherapeutique selectif Download PDF

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Publication number
WO2004111262A1
WO2004111262A1 PCT/IB2004/001975 IB2004001975W WO2004111262A1 WO 2004111262 A1 WO2004111262 A1 WO 2004111262A1 IB 2004001975 W IB2004001975 W IB 2004001975W WO 2004111262 A1 WO2004111262 A1 WO 2004111262A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
deficient
chemotherapeutic agent
agent
cancer
Prior art date
Application number
PCT/IB2004/001975
Other languages
English (en)
Other versions
WO2004111262A8 (fr
Inventor
Roger Lino Yu
Original Assignee
Pharmacia & Upjohn Company Llc
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 Pharmacia & Upjohn Company Llc filed Critical Pharmacia & Upjohn Company Llc
Publication of WO2004111262A1 publication Critical patent/WO2004111262A1/fr
Publication of WO2004111262A8 publication Critical patent/WO2004111262A8/fr

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Classifications

    • 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
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • 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
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/10Screening for compounds of potential therapeutic value involving cells

Definitions

  • the present invention also provides pharmaceutical compositions comprising a therapeutically effective amount of a selective chemotherapeutic agent of the invention, and a pharmaceutically acceptable carrier.
  • the invention also provides a pharmaceutical pack or kit comprising a container containing a pharmaceutical composition comprising a selective chemotherapeutic agent of the invention.
  • the p53 deficient cells and p53 wild-type cells are generally prepared and maintained in cell cultures in suitable culture medium.
  • Cell culture can be prepared and maintained by method known in the art. Any suitable culture medium can be used. Examples of suitable medium include McCoy's medium.
  • suitable medium include McCoy's medium. The cell cultures are incubated under 1 suitable conditions and the test agent, or the vehicle for the agent, is added to the 'cell , te - cultures during incubation.
  • the vehicle control cells are incubated with the vehicle for the test agent, which is the medium wherein the test agent is dissolved, suspended or otherwise prepared prior to being added to the cell culture.
  • the incubation can be carried out under suitable methods and conditions known in the art. Specific conditions of incubation can vary depending various factors known to a person skilled in the art, such as the cell type, and medium compositions. Typically, the incubation is carried out at approximately 37 °C and under a mixture of gas comprising approximately 5% carbon dioxide.
  • the duration of incubation can also vary, mainly depending on types of cells used and other factors, but should be long enough to allow at least two cell cycles, but preferably three or more cell cycles. Typically, the duration of incubation ranges from 24 hours to 48 hours.
  • the selective chemotherapeutic agent causes polyploidy in p53 deficient cells at a rate at least ten-fold higher than in the p53 wild-type cells, more preferred that the selective chemotherapeutic agent causes polyploidy in p53 deficient cells at a rate at least one hundred-fold higher than in the p53 wild-type cells, and even more preferred that the agent causes polyploidy in the p53 deficient cells at a rate that is at least one thousand-fold higher than the agent does in the p53 wild-type cells.
  • Test Compound Preparation Test compound is dissolved in dimethylsulfoxide (DMSO) at the highest concentration on the day of dosing. Lower doses within an assay are serially diluted from the stock concentration and used on the day of dosing.
  • DMSO dimethylsulfoxide
  • the Aroclor induced rat liver S9 fraction is available from Molecular Toxicology, Inc., Boone, North Carolina.
  • the metabolic activation mixture (S9 mix) is prepared fresh on each day of testing and maintained refrigerated prior to testing.
  • the S9 mix consists of the following ingredients (for 110.25.mL): 1.65 mL S 9 homogenate 6.6 mL CORE (filter sterilized) 102 mL serum-free McCoy's medium

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à un procédé d'identification d'un agent chimiothérapeutique sélectif utilisable dans le traitement d'un cancer à déficit de p53. L'invention se rapporte également à un agent chimiothérapeutique sélectif utilisable dans le traitement d'un cancer à déficit de p53. Par ailleurs, l'invention se rapporte à un procédé de traitement d'un patient atteint d'un cancer à déficit de p53 à l'aide d'un agent chimiothérapeutique sélectif.
PCT/IB2004/001975 2003-06-18 2004-06-07 Procede d'identification d'un agent chimiotherapeutique selectif WO2004111262A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US47942403P 2003-06-18 2003-06-18
US60/479,424 2003-06-18

Publications (2)

Publication Number Publication Date
WO2004111262A1 true WO2004111262A1 (fr) 2004-12-23
WO2004111262A8 WO2004111262A8 (fr) 2005-12-01

Family

ID=33551883

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2004/001975 WO2004111262A1 (fr) 2003-06-18 2004-06-07 Procede d'identification d'un agent chimiotherapeutique selectif

Country Status (1)

Country Link
WO (1) WO2004111262A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012121662A1 (fr) * 2011-03-04 2012-09-13 Agency For Science, Technology And Research Nouvelles combinaisons pharmaceutiques et méthodes de traitement du cancer

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5840673A (en) * 1995-09-14 1998-11-24 Bristol-Myers Squibb Company Insulin-like growth factor binding protein 3 (IGF-BP3) in treatment of p53-related tumors

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5840673A (en) * 1995-09-14 1998-11-24 Bristol-Myers Squibb Company Insulin-like growth factor binding protein 3 (IGF-BP3) in treatment of p53-related tumors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TISHLER R B ET AL: "MICROTUBULE-ACTIVE DRUGS TAXOL, VINBLASTINE, AND NOCODAZOLE INCREASE THE LEVELS OF TRANSCRIPTIONALLY ACTIVE P53", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 55, 15 December 1995 (1995-12-15), pages 6021 - 6025, XP002046110, ISSN: 0008-5472 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012121662A1 (fr) * 2011-03-04 2012-09-13 Agency For Science, Technology And Research Nouvelles combinaisons pharmaceutiques et méthodes de traitement du cancer

Also Published As

Publication number Publication date
WO2004111262A8 (fr) 2005-12-01

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Free format text: IN PCT GAZETTE 52/2004 UNDER (72, 75) REPLACE "PHARMACIA & UPJOHN COMPANY" BY "PHARMACIA & UPJOHN COMPANY LLC" AND "YU, RONG" BY "YU, ROGER, LINO"

122 Ep: pct application non-entry in european phase