The Year in Review – ATC 2002

Stock, Peter G.

doi:10.1034/j.1600-6143.2003.00115.x

Cited by 5 publications

(3 citation statements)

References 17 publications

(13 reference statements)

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“…Modulation of immune function has been a successful strategy for treating transplant rejection and autoimmune diseases . However, current therapies also possess significant side effects resulting from the ubiquitous expression of their targets of action .…”

Section: Introductionmentioning

confidence: 99%

Discovery of CP-690,550: A Potent and Selective Janus Kinase (JAK) Inhibitor for the Treatment of Autoimmune Diseases and Organ Transplant Rejection

et al. 2010

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There is a critical need for safer and more convenient treatments for organ transplant rejection and autoimmune disorders such as rheumatoid arthritis. Janus tyrosine kinases (JAK1, JAK3) are expressed in lymphoid cells and are involved in the signaling of multiple cytokines important for various T cell functions. Blockade of the JAK1/JAK3-STAT pathway with a small molecule was anticipated to provide therapeutic immunosuppression/immunomodulation. The Pfizer compound library was screened against the catalytic domain of JAK3 resulting in the identification of a pyrrolopyrimidine-based series of inhibitors represented by CP-352,664 (2a). Synthetic analogues of 2a were screened against the JAK enzymes and evaluated in an IL-2 induced T cell blast proliferation assay. Select compounds were evaluated in rodent efficacy models of allograft rejection and destructive inflammatory arthritis. Optimization within this chemical series led to identification of CP-690,550 1, a potential first-in-class JAK inhibitor for treatment of autoimmune diseases and organ transplant rejection.

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Section: Introductionmentioning

confidence: 99%

Discovery of CP-690,550: A Potent and Selective Janus Kinase (JAK) Inhibitor for the Treatment of Autoimmune Diseases and Organ Transplant Rejection

et al. 2010

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“…The main immunosuppressive agents currently used in organ transplantation, such as cyclosporin A (CyA), tacrolimus, mycophenolate mofetil, and sirolimus, have significant side-effects including nephrotoxicity, neurotoxicity, infection, cancer, new-onset posttransplant diabetes mellitus, hyperlipidemia, and hypertension. − At present there is no antidote for the toxicity of these transplant drugs. Although many treatment options for organ transplant patients have been developed, there remains a great need for effective and safe immunosuppressive agents.…”

mentioning

confidence: 99%

“…[1][2][3][4][5] At present there is no antidote for the toxicity of these transplant drugs. Although many treatment options for organ transplant patients have been developed, 6 there remains a great need for effective and safe immunosuppressive agents.…”

mentioning

confidence: 99%

Synthetic Iminosugar Derivatives as New Potential Immunosuppressive Agents

Sun

Liu

et al. 2005

J. Med. Chem.

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Several iminosugar derivatives were synthesized, and their effects on the secretion of IL-4 and IFN-gamma from the mouse splenocytes were examined. The effects on membrane expression of other T cell-associated molecules (CD3, CD4, CD8) and B cell-associated molecules (CD19) were also investigated. The experimental data demonstrated that synthetic iminosugars hold potential as immunosuppressive agents.

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