Protein kinase C-theta inhibitors: a novel therapy for inflammatory disorders

Curr Pharm Des. 2012;18(30):4725-46. doi: 10.2174/138161212802651625.


PKC-θ is a serine/threonine specific protein kinase and its activation depends upon the concentration of diacylglycerol (DAG) and phospholipids (phosphatidylserine). PKC-θ phosphorylates a variety of proteins that are known to be involved in the diverse cellular signaling pathways. It is predominantly expressed in the T-cells and localized in the center of immunological synapse upon T-cell receptor (TCR) and CD28 signaling. Activation of PKC-θ leads to the activation of various transcription factors in the nuclei of T-cells, e.g. NF-κB, NFAT, c-Jun, c-Fos and AP-1 that further control the proliferation and differentiation of T-cells. Defective T-cell activation in turn leads to the aberrant expression of apoptosis related proteins that cause the poor T-cell survival. Researchers have found that T-cells deficient in PKC-θ exhibit reduced interleukin-2 (IL-2) production. Apart from this role on IL-2 expression, it also plays crucial roles in the proliferation, differentiation and survival of the T-cells, which make it an attractive therapeutic target for a variety of immunological and T-cell mediated diseases. Hence, new molecules capable of modulating the expression or biological activity of PKC-θ are being developed and tested for their potential as novel therapy for several T-cells mediated disease conditions such as multiple sclerosis, rheumatoid arthritis, asthma, inflammatory bowel disease and organ transplantation, etc. In the present review, we tried to integrate the recent discoveries on PKC-θ including its pharmacology and therapeutic potential, along with brief update on its inhibitor molecules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / immunology
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / enzymology
  • Autoimmune Diseases / immunology
  • Catalytic Domain
  • Drug Design
  • Humans
  • Interleukin-2 / immunology
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Kinase C / chemistry
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology


  • Interleukin-2
  • Isoenzymes
  • Protein Kinase Inhibitors
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta