E64FC26 exhibits anti-multiple myeloma (MM) activity with an EC50 of 0.59 μM after 24 hours of treatment in a concentration range of 0.01-100 μM[1]. E64FC26 demonstrates significant cytotoxicity in a panel of genetically diverse multiple myeloma cell lines (KMS11, OPM2, MM.1S BzR, MM.1S, SA-13, U266 BzR, ANBL6, KMS12PE, U266, 8226 DxR, 8226 BzR, KMS12BM, H929, 8226 cells)[1].

In the NSG mouse model, E64FC26 (2 mg/kg; intraperitoneal injection; three times a week for 7 days) demonstrates anti-multiple myeloma (MM) effects, extending the median survival by 2 weeks[1]. The maximum improvement in median survival is observed with both E64FC26 and Bortezomib, leading to a 20-day extension in median survival[1].The pharmacokinetics of E64FC26 were measured in CD-1 mice. E64FC26 was administered via intravenous injection (2 mg/kg; gray trace) or oral administration (5 mg/kg; blue trace), and plasma drug concentrations were measured within 24 hours. In CD-1 mice, after a single oral dose of 5 mg/kg, the maximum concentration (Cmax) reached 400 nM with a terminal half-life of 9.5 hours, demonstrating sufficient oral bioavailability of 34%[1].
Vk*MYC transgenic mice were treated with E64FC26 (2 mg/kg, intraperitoneal injection, 3 days/week) for two consecutive weeks. E64FC26 treatment induces an immediate anti-MM response, resulting in an average reduction of 33 ± 7.9% in serum M protein for all mice[1].