Abstract
Members of the protein kinase C (PKC) family of serine/threonine kinases have been targeted for drug discovery for over 20 years, initially focusing on inhibitors of the classic PKCs, which include the α, β, and γ isoforms. Recently, inhibition of the activity of the novel PKC isoforms, namely θ, δ, η, and η, has become a focus of research. PKCθ, first identified in 1992, is a key enzyme in the regulation of T cell activation and survival. While T cells play critical roles in initiating and controlling the immune response, inappropriate or extended stimulation of T cells is responsible for many chronic inflammatory diseases. Mice with an engineered deficiency in PKCθ have reduced incidence and severity of several inflammatory disorders including asthma, arthritis, inflammatory bowel disease, multiple sclerosis, and allograft rejection. This review summarizes the efforts directed towards the design of small molecule PKCθ inhibitors as potential therapeutic agents.
Keywords: Protein kinase C, PKCθ, inflammatory disease
Current Topics in Medicinal Chemistry
Title: Small Molecule Inhibitors of PKCθ as Potential Antiinflammatory Therapeutics
Volume: 9 Issue: 7
Author(s): Diane H. Boschelli
Affiliation:
Keywords: Protein kinase C, PKCθ, inflammatory disease
Abstract: Members of the protein kinase C (PKC) family of serine/threonine kinases have been targeted for drug discovery for over 20 years, initially focusing on inhibitors of the classic PKCs, which include the α, β, and γ isoforms. Recently, inhibition of the activity of the novel PKC isoforms, namely θ, δ, η, and η, has become a focus of research. PKCθ, first identified in 1992, is a key enzyme in the regulation of T cell activation and survival. While T cells play critical roles in initiating and controlling the immune response, inappropriate or extended stimulation of T cells is responsible for many chronic inflammatory diseases. Mice with an engineered deficiency in PKCθ have reduced incidence and severity of several inflammatory disorders including asthma, arthritis, inflammatory bowel disease, multiple sclerosis, and allograft rejection. This review summarizes the efforts directed towards the design of small molecule PKCθ inhibitors as potential therapeutic agents.
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Boschelli H. Diane, Small Molecule Inhibitors of PKCθ as Potential Antiinflammatory Therapeutics, Current Topics in Medicinal Chemistry 2009; 9 (7) . https://dx.doi.org/10.2174/156802609789007372
DOI https://dx.doi.org/10.2174/156802609789007372 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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