Identification of structurally similar small molecules that enhance therapeutic exon skipping

A composition for enhancing exon skipping in a pre-mRNA of interest, comprising:

• (a) at least one of a compound having a structural similarity to Flupentixol diHCl of 0.65 or greater, wherein the structural similarity is calculated using the algorithm in the ChemmineR package as described in Cao et al. (2008) R. Bio informatics 24, 1733-1734, and
• wherein the compound is at least as effective as Flupentixol diHCl in enhancing exon skipping in the pre-mRNA of interest when an effective amount of the compound is contacted with the pre-mRNA,
• provided that the compound is not Fluphenazine HCl, Trifluoperazine HCl or Piperacetazine,
• or a pharmaceutically acceptable salt, hydrate, solvate, or isomer of the compound;
• and/or
• (b) at least one of a compound having a structural similarity to Corynanthine HCl of 0.65 or greater, wherein the structural similarity is calculated using the algorithm in the ChemmineR package as described in Cao et al. (2008) R. Bio informatics 24, 1733-1734, and
• wherein the compound is at least as effective as Corynanthine HCl in enhancing exon skipping in the pre-mRNA of interest when an effective amount of the compound is contacted with the pre-mRNA,
• provided that the compound is not Yohimbinic Acid M, Yohimbine HCl or Rauwolscine HCl,
• or a pharmaceutically acceptable salt, hydrate, solvate, or isomer of the compound;
• and, in combination with the compound of (a) and/or (b),
• (c) an antisense oligonucleotide (AO) that is specific for an exon that is to be skipped;
• and, optionally,
• (d) a pharmaceutically acceptable carrier.