Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor

By P. Changelian, M. Flanagan, D. Ball, Craig R Kent, K. Magnuson, W. H. Martin, B. Rizzuti, P. Sawyer, Bret D. Perry, W. Brissette and 49 more. Science, 2003

624 citations recorded by the source corpus.

Subfields: Genetics, Oncology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/1427a3fd3415c9898da8e464982a66d7415d98e4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Robert M. Plenge
2. J. O’Shea

In Oncology

1. W. Liao
2. Jian-Xin Lin
3. J. O’Shea
4. A. Laurence
5. W. Leonard
6. T. Malek
7. A. Tedgui
8. Z. Mallat

In Pharmacology

1. Kevan M. Shokat
2. Zachary A. Knight
3. J. O’Shea

Citations in the corpus

• Features of selective kinase inhibitors. (2005, background): “The scale of this investment has led to the discovery of compounds with properties that scarcely resemble their early predecessors—picomolar potency, isoform selectivity, and allosteric binding modes are increasingly common [3–9].”
• Tolerance, not immunity, crucially depends on IL-2 (2004, background): “In some cases, this might be sufficient, because a JAK3-specific inhibitor has been shown to prolong survival of heart and kidney transplant”
• Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy (2013, positive): “Tofacitinib (Changelian et al., 2003; Kremer et al., 2009), which inhibits JAK3 > JAK1 and JAK2 and has also been approved for the treatment of rheumatoid arthritis, based on successful clinical trials (Kontzias et al., 2012), with ongoing Phase III clinical trials for the treatment of psoriasis…”
• Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer (2023, background): “demonstrated the potential benefit of tofacitinib for preventing allograft rejection in vivo by showing that tofacitinib mediated immunosuppression to prevent organ rejection in a murine model of heart transplantation and in a non-human primate model of kidney transplantation.(350) To further explor”
• JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. (2012, background): “Tofacitinib was effective in preclinical models (Changelian et al., 2003) and has shown efficacy in a variety of phase II and III trials in rheumatoid arthritis, as monotherapy and in combination with other drugs (Fleischmann et al., 2012; Kremer et al., 2009, 2012; Tanaka et al., 2011).”
• Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550) (2011, background): “selectivity over JAK2-dependent GM-CSF–driven proliferation of HUO3 cells (18).”
• JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects (2017, background): “Anemia was not observed, consistent with selectivity for JAK3 over JAK2.”
• Cytokines in atherosclerosis: pathogenic and regulatory pathways. (2006, background): “A selective JAK3 antagonist, designated CP-690 550, has recently been developed (115).”
• Janus kinases in immune cell signaling (2009, background): “Efficacy could be shown for preventing heart or kidney rejection after transplantation without observing metabolic abnormalities or severe side effects due to immunosuppression (130).”