S-methyl DM1

S-methyl DM1 is a thiomethyl derivative of Maytansine. S-methyl DM1 binds to tubulin with a K_d of 0.93 μM and inhibts microtubule polymerization. S-methyl DM1 potently suppresses microtubule dynamic instability and has anticancer effects^[1][2]. IC50 & Target:Kd: 0.93 μM (Tubulin)^[1] In Vitro: S-methyl DM1 is the primary cellular or liver metabolite of antibody-maytansinoid conjugates prepared with thiol-containing maytansinoids DM1^[1].
The half-maximal concentration for inhibition of microtubule assembly for for S-methyl DM1 is 4 μM. At 100 nM S-methyl-DM1 (84%) suppresses dynamic instability more strongly than Maytansine (45%). Tritiated S-methyl-DM1 bound to 37 high-affinity sites per microtubule (K_d of 0.1 μM)^[1].
The concentration dependence curves for the inhibition of cell proliferation by S-methyl DM1 is sigmoidal in shape in MCF7 cells. Minimal inhibition occurred at 200 pM S-methyl DM1, and inhibition is maximal at 3 nM. S-methyl DM1 (IC₅₀ of 330 pM) is slightly more potent than Maytansine (IC₅₀ of 710 pM)^[2].
S-methyl DM1 induces maxima of 80% accumulation of cells in G2/M as compared with only 30% in controls in MCF7 cells^[2].