Protein kinase C inhibitors: a patent review (2010 - present).

INTRODUCTION: Protein kinase C (PKC) comprises at least 10 isoforms, pivotal in various cellular differentiation processes and in other specific cellular functions. Catalytic subunits of all PKCs are highly conserved which play a central role in the development of kinase-specific inhibitors for the treatment of a number of diseases and also in the drug resistance and immunological disorders. The authors' previous work of reviewing patents of PKC inhibitors is continued in this report. AREA COVERED: Thorough survey on the physiological roles of PKC isoforms and patents filed for PKC inhibitors from 2010 to present representing new and potential strategy for the cure and prevention of disorders due to elevation in various PKC levels is reported. EXPERT OPINION: The PKC isoforms are unique in terms of tissue distribution and an elevation in any isoform level results in different diseased conditions. Different PKC isoforms have high sequence identity but they are involved in different diseases. Crystal structure of few PKC isoforms viz. C1 domain of PKCδ, the C2 domains of PKCα and ß, kinase domain and full structure of PKCßII are known. Identification of more crystal structures and thorough analysis of available structures and information on the PKC ligands will be helpful in the drug designing and development processes.

Protein kinase C inhibitors: a patent review (2008 - 2009).

INTRODUCTION: The protein kinase C (PKC) is a family of multifunctional isoenzymes involved in apoptosis, migration, adhesion, tumorgenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation. It also plays a vital role in the regulation of signal transduction, cell proliferation and differentiation through positive and negative regulation of the cell cycle. In this work, we reviewed the existing PKC inhibitors and several patents linked to PKC inhibitors. AREAS COVERED: Thorough survey on the PKC inhibitors having clinical importance and patents filed for these inhibitors from 2008 - 2009 is reported. EXPERT OPINION: PKCs are highly potential therapeutic targets for treating diabetic complications, oncological, inflammatory, immunological and dermatological disorders. The clinical trial candidates of PKCs mainly target the catalytic domain, which is highly conserved throughout the PKC family making it difficult to target a particular isoform selectively. Relatively less chemical space and fewer bisubstrate inhibitors targeting both ATP and regulatory domain are explored for PKCs, more research in these areas will be helpful in overcoming existing problems.