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**S-methyl DM4** is a small molecule metabolite formed in vivo from the cytotoxic agent DM4 (ravtansine), a semi-synthetic derivative of maytansine used as a payload in antibody-drug conjugates (ADCs)[2][3][5]. DM4 itself is conjugated to antibodies to target specific cancer cells; after release, DM4 is metabolized in the liver primarily to S-methyl DM4[2][3][5]. S-methyl DM4 binds to tubulin and potently inhibits microtubule assembly and dynamics, similarly to DM4, resulting in cell cycle arrest and apoptosis of rapidly dividing cells[1][2]. It is less potent at inhibiting microtubule polymerization than DM4, but still actively suppresses microtubule dynamics[1][2]. S-methyl DM4 is considered an active metabolite and is implicated in both the efficacy and off-target toxicity of DM4-containing ADCs such as mirvetuximab soravtansine-gynx, anetumab ravtansine, and indatuximab ravtansine[3][5].
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