Bendamustine-d4 (hydrochloride)

Bendamustine-d₄ is intended for use as an internal standard for the quantification of bendamustine by GC- or LC-MS. Bendamustine is a purine analog and DNA alkylating agent.¹ It inhibits growth of SKW-3, Reh, CML-T1, BV-173, and HL-60 leukemia cell lines (IC₅₀s = 27.0, 28.6, 15.6, 20.8, and 57.7 μM, respectively) but not MCF-7 and MDA-MB-231 breast cancer cell lines (IC₅₀s = >200 μM for both).² It is cytotoxic to patient-derived lymphocytic leukemia (B-CLL) cells (LD₅₀s = 6.8-8.3 mg/ml).³ Bendamustine (50 mg/kg) inhibits tumor growth by 9 and 96% alone and in combination with ofatumumab, respectively, in a JVM-3 CLL mouse xenograft model.⁴ It activates the DNA-damage stress response, the base excision DNA repair pathway, and apoptosis, as well as inhibits mitotic checkpoints and induces mitotic catastrophe.¹ Formulations containing bendamustine have been used to treat CLL and non-Hodgkin lymphoma.

1.Leoni, L.M., Bailey, B., Reifert, J., et al.Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agentsClin. Cancer Res.14(1)309-317(2008) 2.Konstantinov, S.M., Kostovski, A., Topashka-Ancheva, M., et al.Cytotoxic efficacy of bendamustine in human leukemia and breast cancer cell linesJ. Cancer Res. Clin. Oncol.128(5)271-278(2002) 3.SchwÄnen, C., Hecker, T., HÜbinger, G., et al.In vitro evaluation of bendamustine induced apoptosis in B-chronic lymphocytic leukemiaLeukemia16(10)2096-2105(2002) 4.Haskova, Z., Whitacre, M.N., Dede, K.A., et al.Combination therapy with ofatumumab and bendamustine in xenograft model of chronic lymphocytic leukaemiaBr. J. Haematol.156(3)402-404(2012)