| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Maytansinoids
Microtubules (tubulin). Maytansinoids, including DM1 (the cytotoxic payload in this linker-payload conjugate), bind to tubulin at the vinca alkaloid binding site, inhibiting tubulin polymerization into microtubules. This disrupts the mitotic spindle formation during cell division, leading to G2/M cell cycle arrest and apoptosis in rapidly dividing cells. The Lys-SMCC-DM1 conjugate is the active metabolite released after intracellular catabolism of T-DM1. |
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| ln Vitro |
As a linker-payload component, (Rac)-Lys-SMCC-DM1 has the potential to inhibit tubulin polymerization. DM1 (the payload) is a potent microtubule polymerization inhibitor with IC50 values in the low nanomolar range (typically 1-5 nM) in tubulin polymerization assays. In cell viability assays, DM1 shows potent cytotoxicity against various cancer cell lines with IC50 values in the sub-nanomolar to low nanomolar range. The racemic form (Rac)-Lys-SMCC-DM1 is used as a research tool to study ADC mechanisms.
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| ln Vivo |
No in vivo activity data is provided for (Rac)-Lys-SMCC-DM1 itself, as it is a linker-payload component used for research. The parent ADC T-DM1 (trastuzumab emtansine) has demonstrated significant in vivo antitumor activity in HER2-positive breast cancer xenograft models and is clinically approved for this indication. T-DM1 combines the HER2-targeting antibody trastuzumab with DM1 via a stable thioether linker (SMCC). After binding to HER2 on cancer cells, T-DM1 is internalized and catabolized in lysosomes, releasing the active metabolite Lys-SMCC-DM1, which then inhibits tubulin polymerization and kills cancer cells.
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| Enzyme Assay |
A tubulin polymerization assay is performed in 96-well plates using purified bovine brain tubulin (>99% pure). Tubulin (2-4 mg/mL) is mixed with varying concentrations of DM1 or Lys-SMCC-DM1 (0.01-100 uM) in polymerization buffer (containing 10% glycerol, 1 mM GTP, 1 mM MgCl2, 80 mM PIPES, pH 6.9). Polymerization is monitored spectrophotometrically at 340 nm (absorbance increases as microtubules form) for 30-60 minutes at 37degC. The EC50 for inhibition of polymerization is calculated. The active Lys-SMCC-DM1 is a more potent inhibitor than the racemic form.
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| Cell Assay |
A cell viability assay is performed in HER2-positive cancer cell lines (e.g., SK-BR-3, BT-474) and HER2-negative control cells (e.g., MDA-MB-231). Cells are seeded in 96-well plates and treated with serial dilutions of Lys-SMCC-DM1 (0.01 nM to 10 uM) or the (Rac)-form as control for 72-96 hours. Cell viability is measured using CellTiter-Glo or MTT assays. Lys-SMCC-DM1 shows potent, HER2-targeted cytotoxicity (IC50 in pM-nM range in HER2-positive cells) due to the targeting effect of the antibody. The racemic form may show different activity.
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| Animal Protocol |
For the parent ADC T-DM1, in vivo efficacy studies are performed in HER2-positive xenograft models. Female SCID or NOD/SCID mice are implanted subcutaneously with HER2-positive human breast cancer cells (e.g., BT-474, SK-BR-3, or HCC1954 cells). When tumors reach approximately 150-200 mm3, mice are randomized and treated intravenously with T-DM1 (doses 1-15 mg/kg) on a Q3D x 4 or Q7D x 3 schedule. Tumor volumes are measured by calipers twice weekly. T-DM1 typically produces significant tumor growth inhibition or regression. The active metabolite Lys-SMCC-DM1 can be quantified in plasma and tumor tissues by LC-MS/MS to study ADC catabolism and payload release.
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| ADME/Pharmacokinetics |
(Rac)-Lys-SMCC-DM1 is soluble in DMSO at 50 mg/mL (45.30 mM). For in vivo formulation, a vehicle of 10% DMSO in corn oil (1.25 mg/mL, 1.13 mM) can be used. The active metabolite is generated intracellularly after T-DM1 catabolism and is not administered directly. As a linker-payload component, it is used for in vitro mechanistic studies and as a reference standard for quantifying the active metabolite in pharmacokinetic studies. Storage: 4degC, stored under nitrogen; In solvent: -80degC for 6 months or -20degC for 1 month (stored under nitrogen).
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| Toxicity/Toxicokinetics |
As a research reagent, toxicity data for (Rac)-Lys-SMCC-DM1 is not publicly available. The parent ADC T-DM1 is clinically approved and has a well-characterized safety profile. Common adverse effects of T-DM1 include thrombocytopenia, increased liver enzymes, fatigue, and nausea. More serious but less common effects include hepatotoxicity (liver injury), cardiotoxicity, and interstitial lung disease. The active metabolite is cytotoxic to dividing cells, including normal cells that express low levels of HER2. (Rac)-Lys-SMCC-DM1 is not intended for human use.
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| References | |
| Additional Infomation |
Lys-SMCC-DM1 is the characterized active metabolite of trastuzumab emtansine (T-DM1, Kadcyla®), an FDA-approved ADC for HER2-positive metastatic breast cancer. T-DM1 consists of the HER2-targeting antibody trastuzumab linked to the maytansinoid payload DM1 via a stable thioether linker (SMCC). After internalization into HER2-expressing cancer cells, T-DM1 is catabolized in lysosomes to release Lys-SMCC-DM1, which is the active form that diffuses into the cytoplasm and binds to tubulin. This product is for research use only and is not FDA-approved for human use.
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| Molecular Formula |
C53H75CLN6O15S
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| Molecular Weight |
1103.71
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| Related CAS # |
Lys-SMCC-DM1;1281816-04-3
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| Appearance |
Off-white to light yellow solid powder
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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 (e.g. under nitrogen), 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 :~50 mg/mL (~45.30 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.13 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 12.5 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 | 0.9060 mL | 4.5302 mL | 9.0604 mL | |
| 5 mM | 0.1812 mL | 0.9060 mL | 1.8121 mL | |
| 10 mM | 0.0906 mL | 0.4530 mL | 0.9060 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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