The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors

Bioorg Med Chem Lett. 2015 Feb 15;25(4):834-40. doi: 10.1016/j.bmcl.2014.12.068. Epub 2014 Dec 30.


The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to tumorigenesis. As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Herein, we describe our efforts toward the development of a potent, pan-Pim inhibitor. The synthesis and hit-to-lead SAR development from a 3-(pyrazin-2-yl)-1H-indazole derived hit 2 to the identification of a series of potent, pan-Pim inhibitors such as 13o are described.

Keywords: Hematologic malignancy; KMS-12; Multiple myeloma; Pim kinase; pan Pim kinase inhibitor.

MeSH terms

  • Drug Discovery
  • Humans
  • Indazoles / chemistry*
  • Indazoles / pharmacology*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Indazoles
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-pim-1
  • proto-oncogene proteins pim