title: 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.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK.
authors.forename: Laura M J
authors.initials: LM
authors.lastname: Kettyle
authors.forename: Fabio G
authors.initials: FG
authors.lastname: Liberante
authors.forename: Alexander
authors.initials: A
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D004195:Disease Models, Animal; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins; D011725:Pyridines; C118739:entinostat