Bendamustine is a DNA cross-linking agent that causes DNA breaks, with alkylating and antimetabolite properties. IC50 & Target: DNA Alkylator/Crosslinker^[1] In Vitro: Bendamustine is a DNA cross-linking agent that causes DNA breaks, with alkylating and antimetabolite properties. Bendamustine uniquely regulates apoptosis pathways and DNA repair pathways in non-Hodgkin's lymphoma cells. Bendamustine (50 μM) induces p21 (Cip1/Waf1) and NOXA genes, and increases the expression of p53 in SU-DHL-1 cells. Bendamustine (25 μM) blocks mitotic checkpoints and cuases mitotic catastrophe^[1]. Bendamustine reduces the viability of multiple myeloma (MM) cell lines, such as RPMI-8226 and 8226-LR5 cells, with IC₂₅s of 101.8 and 585.5 μM after 24 h incubation, and 51.7 and 374.3 μM after 48 h incubation, respectively. Bendamustine induces a specific caspase-dependent MM cell death and inhibits the spindle-assembly checkpoint^[2]. In Vivo: Bendamustine (25 mg/kg, i.v.) shows potent inhibition on the growth of tumor cells by 91%, 99% and 95% for DoHH-2, Granta 519 and RAMOS models, respectively. Moreover, the antitumor effect of Bendamustine is enhanced by rituximab in DoHH-2 and RAMOS models, but not in Granta 519 model^[3].