Methods and compounds for preventing and treating a tumour

摘要

The invention relates to a method of preventing, inhibiting, arresting or reversing tumorigenesis in a cell as well as a method of inducing apoptosis in a tumor cell. The method includes increasing the amount and/or the activity of a DACT protein, or a functional fragment thereof, in the cell. Also provided is a pharmaceutical composition that comprises a compound of general formula (I), wherein A is CH or N, R1, R4 and R5 are independent from each other H, an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, and an arylalicyclic group comprising 0-3 heteroatoms. The heteroatoms may be N, O, S, or Si. R4 and R5 may optionally be linked so as to define an aliphatic hydrocarbyl bridge. R2 is H or a halogen such as F, Cl, Br or L. R3 is H, F, Cl or an aliphatic or arylaliphatic group that includes 1-8 main chain carbon atoms and 0-3 heteroatoms. The pharmaceutical composition also comprises a histone deacetylase inhibitor.;

主权项

1. A method of treating colon cancer, the method comprising:
increasing at least one of the amount and the activity of a DACT3 (“dapper, antagonist of beta-catenin, homolog”) protein, or a functional fragment thereof, wherein the increase in the amount and the activity of the DACT3 protein, or the functional fragment thereof is achieved by administering a combination that increases the expression and/or the activity of the DACT3 protein, or a functional fragment thereof; and wherein the combination is a compound of formula I wherein in formula (I)A is CH,R1, R4 and R5 are independently selected from the group consisting of H and aliphatic,
wherein R4 and R5 may optionally be linked so as to define an aliphatic hydrocarbyl bridge,R2 is selected from the group consisting of H and halogen, andR3 is H, or an aliphatic or arylaliphatic hydrocarbyl group comprising 1-8 main chain carbon atoms and 0-3 heteroatoms selected from the group N, O, S, Si, and halogen;and a histone deacetylase inhibitor, wherein the histone deacetylase inhibitor is a compound of one of the general formula (II) and the general formula (III), wherein R6 is one of H, an amino group, an ether group, an aliphatic group and an arylaliphatic group andL is a bridge comprising an aliphatic or arylaliphatic group comprising 1-8 main chain carbon atoms and 0-3 heteroatoms selected from the group N, O and Si;assessing at least one of the amount and the activity of the DACT3 protein, wherein assessing the amount of the DACT3 protein is achieved by measuring gene expression of the DACT3 protein; andcomparing the result of the measurement of DACT3 gene expression with that of a control measurement.