The Pim kinases: New targets for drug development

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

Research output: Contribution to journalArticle

45 Citations (Scopus)

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
Pages (from-to)2059-2066
Number of pages8
JournalCurrent Drug Targets
Volume12
Issue number14
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

Pharmaceutical Preparations
Sirolimus
Phosphotransferases
Janus Kinase 2
Virus Integration
Moloney murine leukemia virus
Neoplasms
Protein-Serine-Threonine Kinases
Hinges
Viruses
Oncogenes
Protein-Tyrosine Kinases
Tumors
Lymphoma
Carcinogenesis
Leukemia
Adenocarcinoma
Adenosine Triphosphate
proto-oncogene proteins pim
Pharmacology

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

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

The Pim kinases : New targets for drug development. / Swords, Ronan T; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis.

In: Current Drug Targets, Vol. 12, No. 14, 01.12.2011, p. 2059-2066.

Research output: Contribution to journalArticle

Swords, RT, 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, vol. 12, no. 14, pp. 2059-2066. https://doi.org/10.2174/138945011798829447
Swords RT, Kelly K, Carew J, Nawrocki S, Mahalingam D, Sarantopoulos J et al. The Pim kinases: New targets for drug development. Current Drug Targets. 2011 Dec 1;12(14):2059-2066. https://doi.org/10.2174/138945011798829447
Swords, Ronan T ; Kelly, Kevin ; Carew, Jennifer ; Nawrocki, Stefan ; Mahalingam, Devalingam ; Sarantopoulos, John ; Bearss, David ; Giles, Francis. / The Pim kinases : New targets for drug development. In: Current Drug Targets. 2011 ; Vol. 12, No. 14. pp. 2059-2066.
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