Description
NFAT inhibitor is a cell-
permeable compound that selectively inhibits calcineurin-
mediated dephosphorylation of NFAT. At 100 μM, this inhibitor effectively blocks calcineurin binding to NFAT without disrupting other calcineurin-
dependent pathways, unlike the immunosuppressants cyclosporin A and FK506 which indiscriminately block all calcineurin phosphatase activity. NFAT inhibitor can disrupt NFAT-
dependent expression of IL-
2 and TNF-
α when transfected in Jurak T cells and can prevent the activation and proliferation of T cells both
in vitro (~ 43% at 1 μM using mixed lymphocyte cultures) and
in vivo (10 mg/kg using C3H/HeN mice).
Uses
NFAT Inhibitor, VIVIT has been used to study the signaling pathways involved in controlling inhibitory molecules and subsequent onset of T-cell impairment.
Biochem/physiol Actions
High-affinity calcineurin-binding peptide that inhibits NFAT (Nuclear Factor of Activated T cells) activation and NFAT-dependent expression of endogenous cytokine genes in T cells.
References
[1] JOSE ARAMBURU. Affinity-Driven Peptide Selection of an NFAT Inhibitor More Selective Than Cyclosporin A[J]. Science, 1999, 285 5436. DOI:
10.1126/science.285.5436.2129[2] MICHAEL H A ROEHRL. Selective inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with small organic molecules.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101 20: 7554-7559. DOI:
10.1073/pnas.0401835101[3] HAIXIANG YU. Therapeutic potential of a synthetic peptide inhibitor of nuclear factor of activated T cells as antirestenotic agent.[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2006, 26 7: 1531-1537. DOI:
10.1161/01.atv.0000225286.30710.af[4] XUEQIANG ZHAO. JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression[J]. Nature Medicine, 2017, 23 3: 337-346. DOI:
10.1038/nm.4260
