S-methyl DM1

S-methyl DM1 is a thiomethyl derivative of Maytansine. S-methyl DM1 binds to tubulin with a Kd of 0.93 μM and inhibts microtubule polymerization. S-methyl DM1 potently suppresses microtubule dynamic instability and has anticancer effects.

Product information

CAS Number: 912569-84-7

Molecular Weight: 752.31

Formula: C36H50ClN3O10S

Chemical Name: (1S, 2R, 3S, 5S, 6S, 20R, 21S)-11-chloro-21-hydroxy-12, 20-dimethoxy-2, 5, 9, 16-tetramethyl-8, 23-dioxo-4, 24-dioxa-9, 22-diazatetracyclo[19.3.1.1, .0, ]hexacosa-10(26), 11, 13, 16, 18-pentaen-6-yl (2S)-2-[N-methyl-3-(methylsulfanyl)propanamido]propanoate

Smiles: C[C@@]12O[C@H]1[C@H](C)[C@@H]1C[C@@](O)(NC(=O)O1)[C@@H](C=CC=C(C)CC1C=C(C(Cl)=C(C=1)OC)N(C)C(=O)C[C@@H]2OC(=O)[C@H](C)N(C)C(=O)CCSC)OC |c:19,t:17|

InChiKey: PLYHSTGTQYPYMT-UDXCHANISA-N

InChi: InChI=1S/C36H50ClN3O10S/c1-20-11-10-12-27(47-8)36(45)19-26(48-34(44)38-36)21(2)32-35(4,50-32)28(49-33(43)22(3)39(5)29(41)13-14-51-9)18-30(42)40(6)24-16-23(15-20)17-25(46-7)31(24)37/h10-12,16-17,21-22,26-28,32,45H,13-15,18-19H2,1-9H3,(H,38,44)/b12-10-,20-11-/t21-,22+,26+,27-,28+,32+,35+,36+/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

S-methyl DM1 is the primary cellular or liver metabolite of antibody-maytansinoid conjugates prepared with thiol-containing maytansinoids DM1. 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 (Kd of 0.1 μM). 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). S-methyl DM1 induces maxima of 80% accumulation of cells in G2/M as compared with only 30% in controls in MCF7 cells.

References:

1. Lopus M, et al. Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules. Mol Cancer Ther. 2010 Oct;9(10):2689-99.
2. Oroudjev E, et al. Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability. Mol Cancer Ther. 2010 Oct;9(10):2700-13.

Products are for research use only. Not for human use.