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WO2009143078A2 - Procédés de traitement d'un cancer du cerveau à l'aide de composés hexoses - Google Patents

Procédés de traitement d'un cancer du cerveau à l'aide de composés hexoses Download PDF

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Publication number
WO2009143078A2
WO2009143078A2 PCT/US2009/044393 US2009044393W WO2009143078A2 WO 2009143078 A2 WO2009143078 A2 WO 2009143078A2 US 2009044393 W US2009044393 W US 2009044393W WO 2009143078 A2 WO2009143078 A2 WO 2009143078A2
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WO
WIPO (PCT)
Prior art keywords
patient
cancer
cells
compounds
administration
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2009/044393
Other languages
English (en)
Other versions
WO2009143078A9 (fr
Inventor
Waldemar Priebe
Charles Conrad
Timothy Madden
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
University of Texas at Austin
Original Assignee
University of Texas System
University of Texas at Austin
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 University of Texas System, University of Texas at Austin filed Critical University of Texas System
Publication of WO2009143078A2 publication Critical patent/WO2009143078A2/fr
Publication of WO2009143078A9 publication Critical patent/WO2009143078A9/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • FIGs. 1 OA-I OJ show Annexin V staining of U87 cells followed by flow cytometry analysis after 2-DG treatment.
  • the modest increase in annexin V positivity staining confirms that 2-DG primarily acts on U87 cells by inducing autophagy.
  • FIGs. 14A-14C A. Demonstrates the difference in sensitivity of U87 versus D-
  • Hexoses of the present invention may include alpha anomers, beta anomers, and mixtures thereof. Any of the hexoses of the present invention can be optionally substituted. Such substitutions involve replacement of a hydroxyl group with a halogen such as fluorine.
  • substitution is typically at the C-2 carbon of the hexose and may occupy either the axial or equatorial position of a hexose in its 6-membered ring chair conformation.
  • Substitution at C-2 that is axial designates the sugar as a mannose derivative or a sugar of manno configuration.
  • substitution at C-2 that is equatorial designates the sugar as a glucose derivative or a sugar of gluco configuration.
  • the precise amount of compound administered to a patient will be the responsibility of the attendant physician.
  • the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diets, time of administration, route of administration, rate of excretion, drug combination, the precise disorder being treated, and the severity of the indication or condition being treated. Also, the route of administration may vary depending on the condition and its severity.
  • mice treated with 2-DG and Avastin (10 mg/kg body weight) showed an increase in survival rates over individual treatments.
  • the results shown in Figure 6 demonstrate for the single agent efficacy of 2-DG against an orthotopic tumor model. These results were repeated and consistent in three consecutive animal experiments with a total of 18 animals in each group (data not shown). In addition, the combination of 2-DG and Temodar show an enhanced and synergistic effect.
  • the results in Figure 14 illustrate such differential effects of hypoxia more clearly.
  • the MTT assays in Figure 14 demonstrate that D54 cell lines are less sensitive than U87 cell lines to 2-DG treatment under normoxic conditions. However, both cell lines show similar levels of sensitivity to 2-DG treatment under hypoxic conditions.
  • the differential sensitivity of different cell lines to glycolytic inhibitors under hypoxic and normoxic conditions can be correlated with glycolytic activity, as demonstrated by lactate production.
  • the lactate levels for U87 and D54 shown in the chart in Figure 14 demonstrate that U87 cell lines display the same level of glycolytic activity under both hypoxia and normoxia and therefore show substantially the same level of sensitivity to glycolytic inhibitors under both conditions.
  • D54 cells increase their glycolytic activity (as demonstrated by increased lactate levels) under hypoxia and therefore show more sensitivity to glycolytic inhibitors under hypoxic conditions.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des procédés de traitement de gliomes par l'administration à un patient en ayant besoin d'une quantité thérapeutiquement efficace d'un ou plusieurs composés hexoses dans diverses combinaisons avec un ou plusieurs agents anticancéreux, un ou plusieurs agents anti-angiogéniques, un ou plusieurs agents induisant une autophagie et un ou plusieurs agents hypoglycémiques, l'administration d'inhibiteurs glycolytiques à un patient se produisant de préférence après que le patient a jeûné pendant au moins trois jours.
PCT/US2009/044393 2008-05-19 2009-05-18 Procédés de traitement d'un cancer du cerveau à l'aide de composés hexoses Ceased WO2009143078A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5434008P 2008-05-19 2008-05-19
US61/054,340 2008-05-19

Publications (2)

Publication Number Publication Date
WO2009143078A2 true WO2009143078A2 (fr) 2009-11-26
WO2009143078A9 WO2009143078A9 (fr) 2010-03-04

Family

ID=41340807

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/044393 Ceased WO2009143078A2 (fr) 2008-05-19 2009-05-18 Procédés de traitement d'un cancer du cerveau à l'aide de composés hexoses

Country Status (1)

Country Link
WO (1) WO2009143078A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140113930A1 (en) * 2011-06-10 2014-04-24 The Translational Genomics Research Institute Therapeutic combination for cancer treatment
US9504702B2 (en) 2010-08-05 2016-11-29 Seattle Genetics, Inc. Methods of inhibition of protein fucosylation in vivo using fucose analogs
US9816069B2 (en) 2008-05-02 2017-11-14 Seattle Genetics, Inc. Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation
US10350228B2 (en) 2012-08-23 2019-07-16 Seattle Genetics, Inc. Treatment of sickle cell disease and inflammatory conditions

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9816069B2 (en) 2008-05-02 2017-11-14 Seattle Genetics, Inc. Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation
US10443035B2 (en) 2008-05-02 2019-10-15 Seattle Genetics, Inc. Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation
US11319526B2 (en) 2008-05-02 2022-05-03 Seagen Inc. Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation
US9504702B2 (en) 2010-08-05 2016-11-29 Seattle Genetics, Inc. Methods of inhibition of protein fucosylation in vivo using fucose analogs
US10342811B2 (en) 2010-08-05 2019-07-09 Seattle Genetics, Inc. Methods of inhibition of protein fucosylation in vivo using fucose analogs
US11033561B2 (en) 2010-08-05 2021-06-15 Seagen Inc. Methods of inhibition of protein fucosylation in vivo using fucose analogs
US20140113930A1 (en) * 2011-06-10 2014-04-24 The Translational Genomics Research Institute Therapeutic combination for cancer treatment
US9532984B2 (en) * 2011-06-10 2017-01-03 The Translational Genomics Research Institute Therapeutic combination for cancer treatment
US10350228B2 (en) 2012-08-23 2019-07-16 Seattle Genetics, Inc. Treatment of sickle cell disease and inflammatory conditions

Also Published As

Publication number Publication date
WO2009143078A9 (fr) 2010-03-04

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