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Pharmaceutical composition containing insulin-like growth factor-I receptor inhibitor and histon deacetylase (HDAC) inhibitor and application thereof

A technology of receptor inhibitors and sirtuins, applied in drug combinations, medical preparations containing active ingredients, antineoplastic drugs, etc., can solve the problems of patient intolerance and high toxicity

Inactive Publication Date: 2010-06-30
DINKUM INT INVESTMENT HONG KONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, there are many anti-tumor drugs on the market, such as alkylating agent drugs, antimetabolite drugs, anti-tumor antibiotics, immunomodulators, etc., but most of the drugs are more toxic due to large, patient intolerance

Method used

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  • Pharmaceutical composition containing insulin-like growth factor-I receptor inhibitor and histon deacetylase (HDAC) inhibitor and application thereof
  • Pharmaceutical composition containing insulin-like growth factor-I receptor inhibitor and histon deacetylase (HDAC) inhibitor and application thereof
  • Pharmaceutical composition containing insulin-like growth factor-I receptor inhibitor and histon deacetylase (HDAC) inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 The combination of different ratios of BMS-536924 and SAHA synergistically promotes the death of HepG2 cells, see Table 2.

[0063] Table 2

[0064]

[0065] In the experiment investigating the cell death of liver cancer cell line HepG2 caused by related compounds, it was found that when 10.0 μM BMS-536924 or lower concentration and 2.0 μM SAHA or lower concentration were used alone, there was only a small amount of cell death; When used together at a lower concentration (7.5μM BMS-536924+1.25μM SAHA), there is an obvious synergistic effect, resulting in the death of about 55% of cancer cells; when the two are combined at a ratio of 10.0μM BMS-536924+2.0μM SAHA, A more significant synergistic effect is produced, leading to the death of about 90% of cancer cells.

Embodiment 2

[0066] Example 2 The combination of different ratios of BMS-536924 and MS275 synergistically promotes the death of HepG2 cells, see Table 3.

[0067] table 3

[0068]

[0069] In the experiment of investigating the cell death of liver cancer cell line HepG2 caused by related compounds, it was found that when 10.0 μM BMS-536924 or lower concentration and 1.5 μM MS275 or lower concentration were used alone, there was only a small amount of cell death; When used together at a lower concentration (7.5μM BMS-536924+1.0μM MS275), there is an obvious synergistic effect, resulting in about 50% cancer cell death; when the two are combined at a ratio of 10.0μM BMS-536924+1.5μM MS275, A more significant synergistic effect is produced, leading to the death of 90% of cancer cells.

Embodiment 3

[0070] Example 3 The combination of different ratios of BMS-536924 and LBH589 synergistically promotes the death of HepG2 cells, see Table 4.

[0071] Table 4

[0072]

[0073]

[0074] In the experiment investigating the cell death of the liver cancer cell line HepG2 caused by related compounds, it was found that when 10.0 μM BMS-536924 or lower concentration and 0.01 μM LBH589 or lower concentration were used alone, there was only a small amount of cell death; When the concentration reaches 0.02μM LBH589, only about 20% of the cells die; and when the two are used together at a lower concentration (7.5μM LBMS-536924+0.01μM LBH589), there is an obvious synergistic effect, resulting in the death of 52% of the cancer cells ; When the two are combined at the ratio of 10.0μM BMS-536924+0.02μM LBH589, a more significant synergistic effect is produced, resulting in the death of 92% of cancer cells.

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Abstract

The invention relates to a pharmaceutical composition containing an insulin-like growth factor-I receptor inhibitor and a histon deacetylase (HDAC) inhibitor and an application thereof in preparing medicines for treating intestinal cancer, liver cancer, lung cancer, kidney cancer, gastric cancer, brain tumor, sarcoma, pancreatic cancer, ovarian cancer, breast cancer or prostate cancer. The pharmaceutical composition of the invention has obvious synergistic effect, thus improving curative effect of medicines, lowering administration dosage and reducing occurrence of side effect.

Description

technical field [0001] The invention relates to a pharmaceutical composition and its application in the preparation of medicines for treating cancer, in particular to a pharmaceutical composition containing an insulin-like growth factor-I receptor inhibitor and a histone deacetylase inhibitor and its preparation Use in medicines for the treatment of colon cancer, liver cancer, lung cancer, kidney cancer, stomach cancer, brain tumor, sarcoma, pancreatic cancer, ovarian cancer, breast cancer or prostate cancer. Background technique [0002] The survey report of the World Health Organization shows that the global cancer situation is getting worse. In the next 20 years, the number of new patients will increase from the current 10 million to 15 million per year, and the number of deaths from cancer will also increase from 6 million to 10 million per year. Among them, lung cancer is one of the common malignant tumors. It originates from bronchial epithelium at all levels and is di...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/5355A61K31/519A61P35/00A61K31/165A61K31/4045A61K31/4406
Inventor 赵镭
Owner DINKUM INT INVESTMENT HONG KONG
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