EVP4593 is an inhibitor of NF-κB pathway with IC50 value of 11nM [1].

EVP4593 is a quinazoline derivative. It is screened out from a luciferase reporter gene-based assay using human Jurkat T cells. EVP4593 is found as an inhibitor of PMA/PHA-induced NF-κB pathway. It shows significant inhibition of both NF-κB transcriptional activation and TNF-α production (IC50 value of 7nM). Additionally, EVP4593 also has anti-inflammatory efficacy. It inhibits edema formation in a rat carrageenin-induced paw edema model [1].

Since NF-κB pathway may play a direct role in Huntington’s disease (HD) pathogenesis, EVP4593 is found to have beneficial effects in Drosophila HD transgenic model. It significantly slows the progressive decline in the climbing speed without toxic effects [2].

References:
[1] Tobe M, Isobe Y, Tomizawa H, Nagasaki T, Takahashi H, Fukazawa T, Hayashi H. Discovery of quinazolines as a novel structural class of potent inhibitors of NF-kappa B activation. Bioorg Med Chem. 2003 Feb 6;11(3):383-91.
[2] Wu J, Shih HP, Vigont V, Hrdlicka L, Diggins L, Singh C, Mahoney M, Chesworth R, Shapiro G, Zimina O, Chen X, Wu Q, Glushankova L, Ahlijanian M, Koenig G, Mozhayeva GN, Kaznacheyeva E, Bezprozvanny. Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington's disease treatment. Chem Biol. 2011 Jun 24;18(6):777-93.