Abstract
Alternative splicing is a critical step where a limited number of human genes generate a complex and diverse proteome. Various diseases, including inherited diseases with abnormalities in the "genome code," have been found to result in an aberrant mis-spliced "transcript code" with correlation to the resulting phenotype. Chemical compound-based and nucleic acid-based strategies are trying to target this mis-spliced "transcript code". We will briefly mention about how to obtain splicing-modifying-compounds by high-throughput screening and overview of what is known about compounds that modify splicing pathways. The main focus will be on RNA-binding protein kinase inhibitors. In the main text, we will refer to diseases where splicing-modifying-compounds have been intensively investigated, with comparison to nucleic acid-based strategies. The information on their involvement in mis-splicing as well as nonsplicing events will be helpful in finding better compounds with less off-target effects for future implications in mis-splicing therapy.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Alternative Splicing* / drug effects
-
Animals
-
Cytokinins / pharmacology
-
Down Syndrome / drug therapy
-
Dyrk Kinases
-
Dysautonomia, Familial / drug therapy
-
Dysautonomia, Familial / physiopathology
-
HIV Infections / drug therapy
-
HIV Infections / genetics
-
Humans
-
Lung Neoplasms / drug therapy
-
Molecular Targeted Therapy / methods*
-
Muscular Atrophy, Spinal / drug therapy
-
Muscular Atrophy, Spinal / genetics
-
Muscular Dystrophy, Duchenne / drug therapy
-
Myelodysplastic Syndromes / drug therapy
-
Phosphoproteins / antagonists & inhibitors
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein-Tyrosine Kinases / antagonists & inhibitors
-
RNA Splicing Factors
-
RNA-Binding Proteins / antagonists & inhibitors*
-
Ribonucleoprotein, U2 Small Nuclear / antagonists & inhibitors
Substances
-
Cytokinins
-
Phosphoproteins
-
Protein Kinase Inhibitors
-
RNA Splicing Factors
-
RNA-Binding Proteins
-
Ribonucleoprotein, U2 Small Nuclear
-
SF3B1 protein, human
-
Clk dual-specificity kinases
-
Protein-Tyrosine Kinases
-
Protein Serine-Threonine Kinases