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Anti-tumor activity of reduced folates like methylene-tetrahydrofolate

A technology of methyl tetrahydrofolate and tetrahydrofolate, which can be used in antitumor drugs, organic active ingredients, medical preparations containing active ingredients, etc., and can solve problems such as cytotoxicity

Inactive Publication Date: 2014-10-22
ISOFOL MEDICAL AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However antifolates and fluoropyrimidines are cytotoxic and can be associated with serious side effects in many patients

Method used

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  • Anti-tumor activity of reduced folates like methylene-tetrahydrofolate
  • Anti-tumor activity of reduced folates like methylene-tetrahydrofolate
  • Anti-tumor activity of reduced folates like methylene-tetrahydrofolate

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Experimental program
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Embodiment Construction

[0075] Objective: To determine the antitumor efficacy of [6R]-methylene-THF in the HCT116 colorectal cancer xenograft model. The HCT116 colorectal cancer cell line is sensitive to 5-FU and its analog capecitabine.

[0076] Study Design: A total of 30 female NCr nu / nu mice (10 per group) were injected sc in the flank with 5 x 10 6 HCT116 tumor cells. When the tumor reaches 80-120mm 2 According to the schedule in Table 1, they were administered vehicle or [6R]-methylene-THF by intraperitoneal injection Animals were monitored individually. The end point of the experiment is when the tumor weight reaches 1300mm 3 Or 65 days upon arrival, whichever comes first. Respondents can be tracked for longer periods of time. Animals were euthanized when the endpoint was reached. Body weight (bw) (g) and tumor volume (mm 3 ) at 1, 2 (bw only), 3 (bw only), 4, 5 (bw only), 7, 11, 14, 18, 21, 25, 28, 32, 35, 39, 42, 49, 53 , 56, 60 and 63 day measurements.

[0077] Table 1. Treatment...

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Abstract

The present invention relates to the use of reduced folates such as methylene-tetrahydrofolate, tetrahydrofolate or methyl-tetrahydrofolate for use in the treatment of cancer, based on their intrinsic antitumor activity. The cancers that may be treated include breast cancer, gastric cancer, gastrointestinal cancer, gall bladder cancer, bile duct cancer, colon cancer, rectal cancer, liver cancer, pancreatic cancer, head and neck cancer, esophageal cancer, mesotheolioma cancer, lung cancer including non-small-cell lung cancer, ovarian cancer, endometrial cancer, cervicial cancer, peripheral T-cell lymphoma (PTCL), melanoma, brain tumors, adenocarcinoma, esophageal cancer, and osteosarcoma.

Description

field of invention [0001] The present invention relates to reduced folates for use in the treatment of cancer. Background of the invention [0002] Cancer is one of the biggest health problems in the world. It is one of the leading causes of death worldwide, accounting for more than 60% of all deaths worldwide, along with cardiovascular diseases, diabetes, and chronic respiratory diseases. Nearly 12.7 million new cancer cases and 7.6 million cancer deaths occurred worldwide in 2008. [0003] Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Almost 60% of cases occur in developed regions. Incidence rates vary around the world, but are substantially higher in men than in women overall. More than 600,000 people die from the disease each year, accounting for 8% of all cancer-related deaths. In the United States alone, more than 150,000 new cases are diagnosed each year. Colon cancer is defined as cancer that deve...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61P35/00
CPCA61K31/519A61K45/06A61P35/00A61K2300/00
Inventor 本特·古斯塔夫森比约恩·卡尔松
Owner ISOFOL MEDICAL AB