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Medicament composition containing cMet inhibitor, HDAC (Histone Deacetylases) inhibitor and EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and application thereof

A technology of tyrosine kinase and composition, which is applied in the direction of drug combination, medical preparations containing active ingredients, antineoplastic drugs, etc., and can solve problems such as high toxicity and patient intolerance

Inactive Publication Date: 2012-12-12
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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  • Medicament composition containing cMet inhibitor, HDAC (Histone Deacetylases) inhibitor and EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and application thereof
  • Medicament composition containing cMet inhibitor, HDAC (Histone Deacetylases) inhibitor and EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and application thereof
  • Medicament composition containing cMet inhibitor, HDAC (Histone Deacetylases) inhibitor and EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 The combination of different ratios of PF-02341066, SAHA and erlotinib synergistically promotes the death of Hep3B cells, see Table 2.

[0048] Table 2

[0049]

[0050]In the experiment investigating the cell death of the liver cancer cell line Hep 3B caused by related compounds, it was found that when 1.0 μM PF-02341066, 2.0 μM SAHA, 7.5 μM erlotinib or lower concentrations were used alone, there was almost no cell death, even if the above three When any two drugs are combined at lower concentrations, only 1.0μM PF-02341066+1.5μMSAHA, 1.0μM PF-02341066+5.0μM Erlotinib can cause about 15% cell death, while the other combination is 1.5 μM SAHA+5.0 μM erlotinib had almost no cell death; but when these three drugs were combined at the above-mentioned lower concentrations (1.0 μM PF-02341066+1.5 μM SAHA+5.0 μM erlotinib) produced significant Synergistic effect resulted in the death of 43% of cancer cells; when the above three drugs were combined in pairs at h...

Embodiment 2

[0051] Example 2 The combination of different ratios of PF-02341066, SAHA and erlotinib synergistically promotes the death of A549 cells, see Table 3.

[0052] table 3

[0053]

[0054]

[0055] In the experiment investigating the death of lung cancer cell line A549 caused by related compounds, it was found that when 1.5 μM PF-02341066, 1.5 μM SAHA, 5.0 μM erlotinib or lower concentrations were used alone, there was almost no cell death, even if the above three drugs When any two drugs were combined at lower concentrations, no more than 15% of the cells died; Rotinib) produced a significant synergistic effect, resulting in the death of 43% of cancer cells; when the above three drugs were combined in pairs at higher concentrations, only 15-22% of cancer cells died; When used (1.5μMPF-02341066+2.0μM SAHA+7.5μM erlotinib) produced a more significant synergistic effect, resulting in the death of 87% of cancer cells.

Embodiment 3

[0056] Example 3 The combination of different ratios of PF-02341066, SAHA and erlotinib synergistically promotes the death of HCT116 cells, see Table 4.

[0057] Table 4

[0058]

[0059]

[0060] In the experiment investigating the cell death of the colon cancer cell line HCT116 caused by related compounds, it was found that when 1.5 μM PF-02341066, 1.5 μM SAHA or lower concentrations were used alone, there was almost no cell death, even if the single drug concentration of erlotinib was increased by At 7.5μM, only about 15% of the cells died; when any two of the above three drugs were combined at a lower concentration, no more than 15% of the cells died; When used in combination (1.0μMPF-02341066+1.5μMSAHA+5.0μM erlotinib), there was an obvious synergistic effect, resulting in the death of about 43% of cancer cells; when the above three drugs were combined in pairs at higher concentrations , and no more than 20% of cancer cells died; and when the three combined (1.5μMP...

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Abstract

The invention relates to a medicament composition containing a histone deacetylases (HDAC) inhibitor, a hepatocyte growth factor receptor (cMet) inhibitor, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and application thereof in preparing the medicaments for treating liver cancer, lung cancer, colon cancer, kidney cancer, gastric cancer, brain tumor, sarcoma, pancreatic cancer, ovarian cancer, breast cancer or prostatic cancer. The medicament composition has the obvious synergistic effect, improves the curative efficiency of the medicaments, decreases the drug dosage and reduces the occurrence frequency of the 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 composition containing hepatocyte growth factor receptor (cMet) inhibitor, histone deacetylase (HDAC) inhibitor and epidermal growth factor Pharmaceutical composition of receptor (EGFR) tyrosine kinase inhibitor and its use in the preparation of medicines for treating liver cancer, lung cancer, colon cancer, kidney cancer, gastric cancer, brain tumor, sarcoma, pancreatic cancer, ovarian cancer, breast cancer or prostate cancer in the application. 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, primary ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61P35/00
Inventor 赵镭
Owner DINKUM INT INVESTMENT HONG KONG
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