Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of malignancies of the central nervous system in pediatric patients, including glioblastoma multiforme (GBM) high grade glioma, and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation and that can induce double-stranded breaks in DNA. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents (e.g. cisplatin) and can possess additive or super-additive effects.
Type:
Application
Filed:
October 26, 2016
Publication date:
June 13, 2019
Applicant:
DelMar Pharmaceuticals, Inc.
Inventors:
Jeffrey A. Bacha, Dennis M. Brown, Anne Steinø
Abstract: The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol.
Abstract: The present invention is directed to methods for treatment of malignancies in companion animals employing dianhydrogalactitol, diacetyldianhydrogalactitol, and dibromodulcitol, as well as analogs and derivatives thereof, in addition to a method to improve the efficacy and/or reduce the side effects of the administration of a therapeutic agent selected from the group consisting of dianhydrogalactitol, a derivative of dianhydrogalactitol, diacetyldianhydrogalactitol, a derivative of diacetyldianhydrogalactitol, dibromodulcitol, and a derivative of dibromodulcitol to a veterinary subject, the method comprising the steps of: (1 (identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects of the administration of the therapeutic agent to the veterinary subject; and (2) modifying the factor or parameter to improve the efficacy and/or reduce the side effects of the administration of the therapeutic agent to the veterinary subject.
Type:
Grant
Filed:
May 3, 2013
Date of Patent:
November 14, 2017
Assignee:
DELMAR PHARMACEUTICALS, INC.
Inventors:
Jeffrey A. Bacha, Dennis M. Brown, William J. Garner
Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of glioblastoma multiforme. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.
Type:
Grant
Filed:
April 4, 2014
Date of Patent:
June 27, 2017
Assignee:
DELMAR PHARMACEUTICALS, INC.
Inventors:
Jeffrey A. Bacha, Dennis Brown, Sandra Dunn, Anne Steinø
Abstract: The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80° C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol. Another method produces dianhydrogalactitol from dulcitol; this method comprises: (1) reacting dulcitol with a reactant to convert the 1,6-hydroxy groups of dulcitol to an effective leaving group to generate an intermediate; and (2) reacting the intermediate with an inorganic weak base to produce dianhydrogalactitol through an intramolecular SN2 reaction. Other methods for the synthesis of dianhydrogalactitol from dulcitol are described.