SE-7552, a derivative of 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO), serves as an orally active, highly selective non-hydroxamate HDAC6 inhibitor, boasting an IC50 of 33 nM. It exhibits over 850-fold selectivity against all other known HDAC isozymes. Demonstrating efficacy in vivo, SE-7552 effectively inhibits the growth of multiple myeloma. Additionally, it functions as an anti-obesity agent in diet-induced obese mice [1] [2].

HDAC6:33 nM

Administered as a single oral gavage at 30 mg/kg, SE-7552 significantly elevates acetylated α-tubulin levels in mice for over 24 hours, without affecting the acetylation of H3, a Class I HDAC inhibition biomarker [1]. When combined with pomalidomide (1 mg/kg, daily intraperitoneal injection) and given orally at 10 mg/kg daily, SE-7552 markedly delays tumor growth and enhances survival in mice with human H929 MM cells compared to pomalidomide alone [1]. SE-7552 demonstrates excellent pharmacokinetics, with a maximum exposure of 597 ng/ml and a half-life of 7.2 hours following a single oral dose of 5 mg/kg in mice [1].