Nuclear Factor of activated T Cells (NFAT) Activator

CPS-11 (N-(Hydroxymethyl)thalidomide) a Thalidomide (HY-14658) analogue, is a potent anti-cancer agent. CPS-11 inhibits NF-κB, activates NFAT, and repress cytokine expression through elevated ROS. CPS-11 exhibits a wider activity spectrum and higher potency against MM (multiple myeloma) cell lines.

Sulfo galactosylceramide (N-Nervonoyl Sulfatide; C24:1 Sulfatide) is a glycolipid and the major sulfolipid species in mature myelin. Sulfo galactosylceramide interacts with C-type lectins and immunoglobulin-like receptors, with the highest affinity for LMIR5. Sulfo galactosylceramide induces MCP-1 production by basophils but not mast cells, and increases NFAT activation via LMIR5. Sulfo galactosylceramide alleviates symptoms and improves survival in a mouse model of chronic relapsing-remitting experimental autoimmune encephalomyelitis (EAE), and reduces inflammatory lesions and the number of infiltrating mononuclear cells in the lumbar spinal cord of EAE mice.

Centaurein, a flavonoid, is an IFN-γ promoter enhancer. Centaurein up-regulates the activity of NFAT and NF-κB enhancers. Centaurein increases the IFN-γ expression in T and NK cells and the serum IFN-γ level in mice. Centaureidin completely relaxes the contractions in intact rat aortic rings. Centaurein effectively protects mice against Listeria infection^[1][2][3][4].

NUCC-0227579 is a VHL-recruiting PROTAC degrader targeting CD73, with a DC₅₀ of 0.32 μM. NUCC-0227579 synergistically mediates CD73 degradation through the ubiquitin-proteasome pathway and the lysosomal pathway. NUCC-0227579 inhibits the conversion of AMP to adenosine, abrogates adenosine-mediated immunosuppression, upregulates the activities of the NF-κB and NFAT pathways, and enhances the secretion, activation and proliferation levels of IFN-γ and TNF-α. NUCC-0227579 downregulates NAD⁺ synthesis in tumor cells, and inhibits the proliferation, migration and adhesion abilities of tumor cells under glutamine-deficient conditions. NUCC-0227579 significantly suppresses tumor growth in a humanized NSG mouse model of triple-negative breast cancer.