CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders.

Abstract

Pfizer Inc is developing the novel JAK3 inhibitor CP-690550 for the potential prevention of transplant rejection and treatment of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriasis. The benefits of currently available immunosuppressive drugs are countered by numerous side effects, caused mainly by the ubiquitous distribution of the target molecules of these treatments. CP-690550 is expected to overcome these limitations by selectively targeting JAK3, which is expressed generally only in immune cells and is only bound by gamma-chain-bearing cytokine receptors involved in the JAK/STAT signaling pathway. CP-690550 exhibited potent immunosuppressive activity in preclinical models of RA and organ transplant rejection. Phase I and II clinical trials demonstrated the efficacy and safety of CP-690550 in preventing transplant rejection and alleviating the symptoms of RA and psoriasis. At the time of publication, CP-690550 was in phase II/III trials in patients with RA, phase II trials in patients with psoriasis, ulcerative colitis and Crohn's disease, and transplant recipients, and a phase I/II trial for dry eye disease (xerophthalmia). Thus, the preclinical and clinical data strongly support the use of CP-690550 to produce sufficient immunosuppression to prevent organ transplant rejection and to treat autoimmune diseases; CP-690550 could herald the beginning of a new generation of safe and effective immunosuppressive therapies.

• Authors: Kevin West
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 10 Issue 5 Pg. 491-504 (May 2009) ISSN: 2040-3429 [Electronic] England
• PMID: 19431082 (Publication Type: Journal Article, Review)

Chemical References

• Immunosuppressive Agents
• Piperidines
• Protein Kinase Inhibitors
• Pyrimidines
• Pyrroles
• tofacitinib
• Janus Kinase 3

Topics

• Animals
• Arthritis, Rheumatoid (drug therapy, enzymology, immunology)
• Clinical Trials as Topic (methods)
• Drug Evaluation, Preclinical (methods)
• Graft Rejection (drug therapy, enzymology, immunology)
• Humans
• Immunosuppressive Agents (chemistry, pharmacology, therapeutic use)
• Janus Kinase 3 (antagonists & inhibitors)
• Piperidines
• Protein Kinase Inhibitors (chemistry, pharmacology, therapeutic use)
• Psoriasis (drug therapy, enzymology, immunology)
• Pyrimidines (chemistry, pharmacology, therapeutic use)
• Pyrroles (chemistry, pharmacology, therapeutic use)