Method for screening substance capable of inhibiting abnormal splicing causative of onset or progress of disease
A compound and a pharmaceutical composition for disease associated with an abnormal splice variant, use of the compound and the pharmaceutical composition, or a screening method of the compound and the pharmaceutical composition are provided. One or more embodiments disclose a compound expressed by the following formula (I) or (I′) or prodrugs or pharmaceutically acceptable salts thereof. Another one or more embodiments disclose a screening method using a DNA construct that is fused, arranged, or constructed so as to express different reporter genes for a wild-type splice variant and an abnormal splice variant that contributes to the development or progression of disease;
1. A pharmaceutical composition containing a compound expressed by the following formula (I) or (I′) or the pharmaceutical acceptable salts thereof as an active ingredient useful in a method of altering splicing of a pre-mRNA of a mutant IKBKAP gene having a IVS20+6T-C mutation in human cells or human individuals; increasing a ratio of wild-type splicing to abnormal splicing of a pre-mRNA of a mutant IKBKAP gene having a IVS20+6T-C mutation in human cells or human individuals; or increasing a proportion of exon 20 present in an mRNA that is transcribed from a mutant IKBKAP gene having a IVS20+6T-C mutation in human cells or human individuals,
wherein, in the formulas (I) and (I′),
R 1 represents a heteroarylmethyl group,
R 2 represents a hydrogen atom,
R 3 represents a hydrogen atom and
X represents a halogen atom.
2. The pharmaceutical composition according to claim 1 , wherein the cells are neurons, cancer cells, or infected cells.
3. The pharmaceutical composition according to claim 1 , for preventing, improving, inhibiting progression of, and/or treating genetic disease.
4. The pharmaceutical composition according to claim 1 , wherein the halogen atom is a fluorine atom or a chlorine atom.
5. The pharmaceutical composition according to claim 1 , wherein the compound is the compound expressed by the following formula (II):
wherein Y represents a halogen atom.