DM4 is a thiol-containing derivative of the tubulin polymerization inhibitor maytansine.1,2 It is cytotoxic to SK-BR-3 cells (IC50 = 3.3 nM).1 DM4, conjugated to a humanized CD205-targeting monoclonal antibody, is selectively cytotoxic to a variety of CD205-expressing human cancer cells (EC50s = 0.1-1.32 nM) over non-CD205-expressing cells (EC50s = 14.2-22.66 nM) and reduces tumor growth in various mouse xenograft and patient-derived (PDX) cancer models.3
1.Widdison, W.C., Wilhelm, S.D., Cavanagh, E.E., et al.Semisynthetic maytansine analogues for the targeted treatment of cancerJ. Med Chem.49(14)4392-4408(2006) 2.Remillard, S., Rebhun, L.I., Howie, G.A., et al.Antimitotic activity of the potent tumor inhibitor maytansineScience189(4207)1002-1005(1975) 3.Merlino, G., Fiascarelli, A., Bigioni, M., et al.MEN1309/OBT076, a first-in-class antibody-drug conjugate targeting CD205 in solid tumorsMol. Cancer Ther.18(9)1533-1543(2019)