title: Targeting Pim kinases for cancer treatment: opportunities and challenges.
abstract: Pim oncogenes are highly expressed in many types of hematological and solid cancers. Pim kinases regulate the network of signaling pathways that are critical for tumorigenesis and development, making Pim kinases the attractive drug targets. Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. In this review, we summarize the current progress in understanding the Pim-related structure and biology, and provide insights into the binding modes of some prototypical Pim-1 inhibitors. The challenges as well as opportunities are highlighted for development of Pim kinase inhibitors as potential anticancer agents.
authors.affiliation: Centre for Drug Discovery & Development, Sansom Institute for Health Research, & School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Bich Thuy
authors.initials: BT
authors.lastname: Le
authors.forename: Malika
authors.initials: M
authors.lastname: Kumarasiri
authors.forename: Julian R J
authors.initials: JR
authors.lastname: Adams
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Yu
authors.forename: Robert
authors.initials: R
authors.lastname: Milne
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sykes
authors.forename: Shudong
authors.initials: S
authors.lastname: Wang
mesh_terms: D001667:Binding, Competitive; D004353:Drug Evaluation, Preclinical; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim