title: The in vivo evaluation of active-site TOR inhibitors in models of BCR-ABL+ leukemia.
abstract: Preclinical evaluation of candidate anticancer compounds requires appropriate animal models. Most commonly, solid tumor xenograft systems are employed in which immunocompromised mice are implanted with human cancer cell lines. Genetically engineered mouse models of solid tumors are also frequently employed. Both of these approaches can also be applied to studies of hematological malignancies. In this chapter, we describe three types of mouse models of leukemia driven by the human BCR-ABL oncogene. We also discuss the application of these models to preclinical testing of active-site TOR inhibitors, a novel class of compounds that selectively target the ATP-binding pocket of the target of rapamycin (TOR) kinase.
authors: Drug Discovery, Intellikine Inc., La Jolla, CA 92037, USA.
authors: Matthew R
authors: MR
authors: Janes
authors: David A
authors: DA
authors: Fruman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C500984:CRTC1 protein, human; C493245:CRTC2 protein, human; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D016044:Fusion Proteins, bcr-abl