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Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor

a technology combination drugs, which is applied in the direction of heterocyclic compound active ingredients, drug compositions, organic active ingredients, etc., can solve problems such as resistance and achieve the effect of reducing the ras-gtp loading potential of cells and amplifying the anti-proliferation effect of anaplastic lymphoma kinas

Inactive Publication Date: 2019-11-14
THE GENERAL HOSPITAL CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention is about using two drugs to treat cancer, specifically lung cancer that is caused by a specific genetic change called ALK rearrangement. These drugs target both ALK and another protein called SHP2. Combining them can inhibit the growth of cancer cells, even when the cancer is resistant to treatment with another drug. This suggests that this combination could be an effective way to treat resistant cancer.

Problems solved by technology

However, in spite of these treatment options cases of resistance occur.

Method used

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  • Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor
  • Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor
  • Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor

Examples

Experimental program
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Effect test

embodiment 1

[0188]A pharmaceutical combination comprising:[0189](i) an ALK inhibitor, or a pharmaceutically acceptable salt thereof, selected from 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine (ceritinib), 9-Ethyl-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (alectinib) and (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,1]-benzoxadiazacyclotetradecine-3-carbonitrile (loratinib), and[0190](ii) a SHP2 inhibitor, or a pharmaceutically acceptable salt thereof.

embodiment 2

[0191]A pharmaceutical combination comprising:[0192](i) an ALK inhibitor, or a pharmaceutically acceptable salt thereof, selected from 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine (ceritinib), 9-Ethyl-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (alectinib) and (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,1]-benzoxadiazacyclotetradecine-3-carbonitrile (loratinib), and[0193](ii) a SHP2 inhibitor of Table 1, or a pharmaceutically acceptable salt thereof,

TABLE 1Com-poundNo.StructureName16-(4-amino-4-methylpiperidin- 1-yl)-3-(2,3- dichlorophenyl)pyrazin-2- amine26-(4-aminomethyl)-4- phenylpiperidin-1-yl)-3-(2,3- dichlorophenyl)pyrazin-2- amine36-(4-(aminomethyl)-4- methylpiperidin-1-yl)-3-(2,3- dichlorophenyl)pyrazin-2- amine46-(4-(aminomethyl)-4- methylpiperidin-1-yl)-3-((2- (trifluoromethyl)pyri...

embodiment 3

[0194]The pharmaceutical combination of Embodiment 1 or Embodiment 2, wherein the ALK inhibitor is 5-chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine (ceritinib), or a pharmaceutically acceptable salt thereof.

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Abstract

A pharmaceutical combination comprising an ALK inhibitor, in free form or a pharmaceutically acceptable salt thereof, and a SHP2 inhibitor, in free form or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, for simultaneous or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a pharmaceutical combination comprising an anaplastic lymphoma kinase (ALK) inhibitor as one of the combination partners, the uses of such a combination in the treatment of proliferative diseases, such as cancer, in particular non-small cell lung cancer (NSCLC); and methods of treating a subject suffering from a proliferative disease, such as cancer, in particular non-small cell lung cancer, comprising administering a therapeutically effective amount of such a combination.BACKGROUND OF THE INVENTION[0002]Highly potent and selective inhibitors targeting anaplastic lymphoma kinase (ALK)-rearranged lung cancer have been used to treat patients suffering from non-small cell lung cancer (NSCLC). However, in spite of these treatment options cases of resistance occur. The resistance to the selective inhibitors can develops through a variety of mechanisms, such as for example through secondary mutations in ALK, or activation of a c...

Claims

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Application Information

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IPC IPC(8): A61K31/506A61K31/5377A61K31/4545A61K31/53A61K31/519A61K31/497A61P35/00
CPCA61K31/497A61K31/4545A61K31/506A61P35/00A61K31/53A61K31/5377A61K31/519A61K45/06A61K31/4353A61K31/4439A61K31/513A61K31/5375A61P35/02A61P43/00A61K2300/00A61K31/675A61K31/4985
Inventor ALGHALANDIS, LEILA DARDAEIENGELMAN, JEFFREY ADAMHAO, HUAIXIANGLAMARCHE, MATTHEW J.LI, FANGWANG, HUI-QIN
Owner THE GENERAL HOSPITAL CORP
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