| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
S-methyl DM1 targets microtubules, specifically binding to the tubulin subunit at the maytansine binding site. It inhibits microtubule polymerization, leading to G2/M cell cycle arrest and apoptosis. Unlike DM1, S-methyl DM1 cannot be conjugated to antibodies via disulfide bonds because the thiol is blocked; it thus serves as a non-conjugatable control to study the contribution of linker chemistry to ADC activity.
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| ln Vitro |
The primary metabolite of antibody-maytansinoid conjugates made with the thiol-containing maytansinoid DM1 is S-methylDM1 in the cell or liver [1]. Microtubule assembly is inhibited by S-methylDM1 at a half-maximal dose of 4 μM. Dynamic instability was decreased more by 100 nM S-methyl-DM1 (84%) than by maytansine (45%). 37 high-affinity sites per microtubule (Kd 0.1 μM) are bound by tritiated S-methyl-DM1 [1]. The concentration-dependent curve of S-methylDM1, which inhibits cell growth, was formed like a S in MCF7 cells. S-methylDM1 had a negligible inhibitory effect at 200 pM and a peak inhibitory effect at 3 nM. The potency of S-methyl DM1 (IC50 = 330 pM) is somewhat higher than that of maytansine (IC50 = 710 pM) [2]. S-methylDM1 increased the amount of cells in MCF7 cells to a maximum of 80% in the G2/M phase, while the control group only had 30% of this amount [2].
In vitro, S-methyl DM1 retains potent cytotoxicity against cancer cell lines, with IC50 values in the low nanomolar to picomolar range (e.g., 0.1-10 nM in HER2-positive cells like SK-BR-3 and BT-474). It is generally 2-10 times less potent than unconjugated DM1 due to the methyl group slightly reducing tubulin binding affinity. It induces G2/M arrest and apoptosis in a similar manner to DM1. |
| ln Vivo |
No specific in vivo activity data is available for S-methyl DM1 alone. As a control compound, it is sometimes used in xenograft models to demonstrate that the activity of an ADC (trastuzumab emtansine) depends on the intact conjugate rather than free DM1 released from the ADC. At equimolar doses, S-methyl DM1 is less effective than DM1 due to altered pharmacokinetics, but it can still inhibit tumor growth at sufficient doses (e.g., 1-5 mg/kg i.v.).
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| Enzyme Assay |
For tubulin binding assays: Purify bovine brain tubulin. Incubate tubulin (2 uM) with various concentrations of S-methyl DM1 (0.1-100 nM) in PEM buffer (80 mM PIPES, 1 mM EGTA, 1 mM MgCl2, pH 6.8) containing 1 mM GTP and 10% glycerol. Induce polymerization by adding 10 uM paclitaxel or by warming to 37degC. After 30 min, centrifuge to pellet polymerized tubulin. Quantify tubulin in supernatant and pellet by SDS-PAGE or Bradford assay. Alternatively, measure fluorescence using a tubulin polymerization assay kit.
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| Cell Assay |
For cytotoxicity assays: Culture HER2-positive (SK-BR-3, BT-474) and HER2-negative (MDA-MB-468) breast cancer cells in recommended media. Seed cells in 96-well plates (5,000 cells/well). After 24 h, treat with serial dilutions of S-methyl DM1 (0.001 nM to 1 uM) for 72-96 hours. Add MTT or CellTiter-Glo reagent. Measure absorbance or luminescence. Calculate IC50 values using nonlinear regression. For cell cycle analysis, treat cells with 10 nM S-methyl DM1 for 24 h, fix in 70% ethanol, stain with propidium iodide, and analyze by flow cytometry.
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| Animal Protocol |
No specific in vivo protocol exists for S-methyl DM1 alone. For xenograft studies: Subcutaneously inoculate athymic nude mice with BT-474 or NCI-N87 cells (5-10 million cells per mouse). When tumors reach ~150-200 mm3, administer S-methyl DM1 intravenously at doses of 1-5 mg/kg (in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) once weekly for 3 weeks. Measure tumor volumes twice weekly. Compare to vehicle, unconjugated DM1, and the corresponding ADC. Monitor body weight for toxicity.
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| ADME/Pharmacokinetics |
S-methyl DM1 is expected to have pharmacokinetic properties similar to other small-molecule maytansinoids: high plasma protein binding (>90%), rapid distribution into tissues, and a plasma half-life of 1-3 hours in mice. The methyl group prevents disulfide exchange with plasma proteins, unlike DM1 which can form mixed disulfides. S-methyl DM1 is metabolized primarily by CYP3A4 in the liver. It is excreted in bile and feces.
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| Toxicity/Toxicokinetics |
The toxicity profile of S-methyl DM1 is similar to that of other maytansinoids, primarily causing bone marrow suppression (neutropenia, thrombocytopenia), gastrointestinal toxicity (diarrhea, nausea), and peripheral neuropathy at higher doses. In animal studies, the maximum tolerated dose (MTD) in mice is approximately 5-10 mg/kg (single i.v.). At doses above MTD, severe weight loss and mortality occur. Use extreme caution when handling; maytansinoids are highly potent cytotoxins.
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| References |
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| Additional Infomation |
S-methyl DM1 is a research-grade compound used as a reference standard and control in ADC development. It is not a therapeutic agent. The compound is supplied as a lyophilized powder or in DMSO solution. Store at -80degC for long-term stability. Handle with extreme care due to high cytotoxicity; use double gloves and work in a biosafety cabinet. Follow appropriate disposal procedures for cytotoxic agents. No clinical trials involve this specific compound.
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| Molecular Formula |
C36H50CLN3O10S
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|---|---|
| Molecular Weight |
752.314308643341
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| Exact Mass |
751.29
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| CAS # |
912569-84-7
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| PubChem CID |
89629084
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
51
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| Complexity |
1350
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| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@@]12O[C@H]1[C@@H]([C@@]1([H])OC(=O)N[C@]([C@@]([H])(C=CC=C(C)CC3C=C(OC)C(Cl)=C(C=3)N(C)C(=O)C[C@]2([H])OC(=O)[C@H](C)N(C)C(=O)CCSC)OC)(O)C1)C |c:17,t:15,&1:1,3,4,5,11,12,34,39|
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| InChi Key |
PLYHSTGTQYPYMT-JLZGXKMHSA-N
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| InChi Code |
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
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| Chemical Name |
[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[methyl(3-methylsulfanylpropanoyl)amino]propanoate
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| Synonyms |
Smethyl DM1; S methyl DM1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~132.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3292 mL | 6.6462 mL | 13.2924 mL | |
| 5 mM | 0.2658 mL | 1.3292 mL | 2.6585 mL | |
| 10 mM | 0.1329 mL | 0.6646 mL | 1.3292 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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