Rational drug repurposing using sscMap analysis in a HOX-TALE model of leukemia.

Abstract

Drug discovery and development are often hampered by lack of target identification and clinical tractability. Repurposing of approved drugs to life-threatening diseases such as leukemia is emerging as a promising alternative approach. Connectivity mapping systems link approved drugs with disease-related gene signatures. Relevant preclinical models provide essential tools for system validation and proof-of-concept studies. Herein we describe procedures aimed at generating disease-based gene signatures and applying them to established cross-referencing databases of potential candidate drugs. As a proof of principle, we present the identification of Entinostat as a candidate drug for the treatment of HOX-TALE-related leukemia.

• Authors: Laura M J Kettyle, Fabio G Liberante, Alexander Thompson
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 1196 Pg. 349-70 ( 2014) ISSN: 1940-6029 [Electronic] United States
• PMID: 25151174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Histone Deacetylase Inhibitors
• Homeodomain Proteins
• Pyridines
• entinostat

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Benzamides (administration & dosage, pharmacology)
• Cell Line, Tumor
• Databases, Genetic
• Disease Models, Animal
• Drug Discovery
• Drug Evaluation, Preclinical
• Gene Expression Profiling
• Gene Expression Regulation, Leukemic (drug effects)
• Histone Deacetylase Inhibitors (administration & dosage, pharmacology)
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Leukemia (drug therapy, genetics, metabolism, pathology)
• Mice
• Pyridines (administration & dosage, pharmacology)
• Xenograft Model Antitumor Assays