BBDDL2059 is a selective covalent inhibitor of EZH2 with an IC50 of 1.5 nM against the EZH2-Y641F mutant, demonstrating nanomolar potency in inhibiting lymphoma cell proliferation, thereby proving its utility in anticancer research [1].

EZH2 (Y641F):1.5 nM

BBDDL2059 (Compound 16) at concentrations ranging from 0-65 nM over 6 days inhibits the growth of KARPAS-422 and Pfeiffer cells [1]. Moreover, BBDDL2059 at doses between 0-1 µM for 48-96 hours suppresses EZH2 enzymatic activity and sustains long-term inhibition of EZH2 following washout [1].

BBDDL2059 (Compound 16) demonstrated a pharmacokinetic profile in rats, with a half-life (T 1/2) of 0.28 hours following an intravenous dose of 3 mg/kg and an oral bioavailability (F%) of 0.05% at a 10 mg/kg oral dose [1]. The respective pharmacokinetic parameters for intravenous administration were a maximum concentration (Cmax) of 4886 ng/mL, an area under the curve (AUC0-last) of 11.1 h•ng/mL, a clearance (CL) of 161 mL•min^-1/kg^-1, and a steady-state volume of distribution (Vss) of 11.1 L/kg. The oral dose resulted in a Cmax of 29.5 ng/mL and an AUC0-last of 8.16 h•ng/mL [1].