The Pim kinases: New targets for drug development

Ronan Swords, Kevin Kelly, Jennifer Carew, Stefan Nawrocki, Devalingam Mahalingam, John Sarantopoulos, David Bearss, Francis Giles

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin. Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.

Original languageEnglish (US)
Pages (from-to)2059-2066
Number of pages8
JournalCurrent drug targets
Volume12
Issue number14
DOIs
StatePublished - Dec 1 2011

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Keywords

  • Akt
  • Cell signalling
  • Drug development
  • Kinase
  • PI3 kinase
  • PIM kinase
  • mTOR

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Swords, R., Kelly, K., Carew, J., Nawrocki, S., Mahalingam, D., Sarantopoulos, J., Bearss, D., & Giles, F. (2011). The Pim kinases: New targets for drug development. Current drug targets, 12(14), 2059-2066. https://doi.org/10.2174/138945011798829447