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Dianhydrogalactitol together with radiation to treat non-small-cell carcinoma of the lung and glioblastoma multiforme

A kind of non-small cell lung cancer, the technology of two dehydrated dulcitol, applied in the generation of hexitol and its field

Inactive Publication Date: 2017-10-03
DEL MAR PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the treatments that are often tried are chemotherapy and radiation therapy, especially if the diagnosis cannot be made at an early stage of malignancy

Method used

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  • Dianhydrogalactitol together with radiation to treat non-small-cell carcinoma of the lung and glioblastoma multiforme
  • Dianhydrogalactitol together with radiation to treat non-small-cell carcinoma of the lung and glioblastoma multiforme
  • Dianhydrogalactitol together with radiation to treat non-small-cell carcinoma of the lung and glioblastoma multiforme

Examples

Experimental program
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Effect test

Embodiment 1

[1170] In vivo efficacy of dianhydrodulcitol in the treatment of non-small cell lung cancer using a mouse xenograft tumor model

[1171] background

[1172]The median overall survival time of patients with stage IV non-small cell lung cancer (NSCLC) is 4 months, and the 1-year and 5-year survival rates are less than 16% and 2%, respectively. NSCLC is usually treated with surgery followed by either tyrosine kinase inhibitor (TKI) (eg, erlotinib, gefitinib) treatment or platinum-based regimens (eg, cisplatin). TKIs have resulted in greatly improved outcomes for patients with EGFR mutations; however, TKI resistance has become a significant unmet medical need, and platinum-based therapies have a poor long-term prognosis. In addition, the incidence of brain metastases is higher in NSCLC patients and the prognosis is poorer.

[1173] Didodulcitol is a structurally unique bifunctional alkylating agent that targets the N of guanine 7 It mediates cross-linking between DNA strands,...

Embodiment 2

[1222] Response of primary glioblastoma multiforme cultures to didiodulcitol treatment with or without radiation answer

[1223] The standard of care for patients with glioblastoma multiforme (GBM) is surgical resection followed by temozolomide (TMZ) and radiation (XRT). TMZ is for presenting O 6 - Most effective in a minority of patients with epigenetic inactivation of O6-methylguanine DNA methyltransferase (MGMT), which removes methyl additions caused by TMZ Complex DNA repair enzymes. Thus, adducting DNA repair mechanisms that are not subject to MGMT may have additional benefits for GBM patients, most of whom express MGMT resistance or TMZ resistance, or acquire resistance after TMZ administration. The N7 alkylating agent, didhydrodulcitol ("VAL-083") is not subject to MGMT-mediated repair and thus may be a more effective chemotherapeutic agent. Dinghydrodulcitol is a first-in-class first-in-class alkylating agent that crosses the blood-brain barrier and is currently...

Embodiment 3

[1260] Treatment of Patients with Recurrent Malignant Glioma or Progressive Secondary Brain Tumors with Didodulcitol

[1261] Brain tumors are among the most challenging malignancies. For glioblastoma multiforme (GBM), the median survival rate for patients with recurrent disease is less than 6 months. Central nervous system (CNS) metastases have evolved to be a major contributor to cancer mortality because of the lack of access to improved systemic treatment of tumors that spread to the brain.

[1262] Frontline systemic therapy is temozolomide, but due to O 6 - Resistance caused by methylguanine-DNA-methyltransferase (MGMT) activity has been implicated in adverse outcomes. This resistance greatly reduces survival rates.

[1263] Dinghydrodulcitol is the first-in-class first-in-class bifunctional N that easily crosses the blood-brain barrier and accumulates in brain tissue 7 DNA alkylating agent. dianhydrodulcitol in N 7 - Guanine causes DNA interstrand crosslinks (E.I...

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Abstract

The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and for the treatment of glioblastoma multiforme (GBM). 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.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of J.A. Basha et al., filed on November 10, 2014, entitled "Di-dehydrated Hydroxyl in Combination with Radiation for the Treatment of Non-Small Cell Lung Cancer and Glioblastoma Multiforme and Inhibition of Proliferation of Cancer Stem Cells" Alcohols and Their Analogues and Derivatives Uses," U.S. Provisional Patent Application Serial No. 62 / 077,712, the contents of which are incorporated herein by reference. technical field [0003] The present invention relates to the general field of proliferative diseases including oncology, the present invention focuses on novel methods and compositions for the improved utility of chemical agents, compounds and dosage forms previously limited by unsatisfactory human therapeutic effects, said Chemical agents, compounds and dosage forms include substituted hexitols such as dianhydrodulcitol and diacetyldidedulcitol, as well as other classes of chem...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/336A61K35/00C07D303/02
CPCA61K45/06A61K38/38A61K31/336A61P11/00A61P25/00A61P3/00A61P35/00A61P35/04A61P37/04A61P43/00A61K2300/00
Inventor 杰佛利·A·巴察丹尼斯·M·布朗安妮·斯提努肖恩·福斯
Owner DEL MAR PHARMA
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