PCI-32765: a novel Bruton's tyrosine kinase inhibitor for the treatment of lymphoid malignancies

Expert Opin Investig Drugs. 2012 Mar;21(3):355-61. doi: 10.1517/13543784.2012.656199. Epub 2012 Feb 3.


Introduction: There has been a significant paradigm shift in the manner in which lymphoid malignancies are treated and managed. Treatment has been moving away from conventional chemotherapy and towards targeted therapy. The success of new classes of agents such as monoclonal antibodies, proteasome inhibitors and immunomodulatory derivatives has sparked further searches for novel pathways to inhibit. The Bruton's tyrosine kinase (Btk) pathway is a downstream mediator of the B-cell receptor (BCR) pathway, which is crucial in B-cell production and maintenance, and a potential therapeutic target.

Areas covered: This review will summarize the current knowledge of the Btk pathway and its role in lymphoid malignancies. It will also discuss the present data about PCI-32765 in both the preclinical and clinical setting.

Expert opinion: PCI-32765 is an oral irreversible Btk inhibitor with high potency and both preclinical and clinical activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Phase I studies have demonstrated that it is well tolerated and has an excellent safety profile. Further studies are ongoing as a single agent and in combination with other targeted and conventional therapies. PCI-32765 is a very promising targeted therapy, and the data from these trials will ultimately decide its future role and success.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • B-Lymphocytes / metabolism
  • Drug Delivery Systems
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / pathology
  • Piperidines
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*


  • Antineoplastic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Adenine