| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
Maytansinoids; MC-DM1 targets tubulin via its DM1 moiety. DM1 is a derivative of maytansine, a potent inhibitor of microtubule polymerization, which binds to tubulin at the maytansine-binding site, preventing microtubule assembly and thereby inhibiting cell division, selectively blocking the proliferation of rapidly dividing cancer cells.
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| ln Vitro |
In conjugated form with antibodies, MC-DM1 exhibits potent cytotoxicity against various cancer cell lines. Anti-CD79b-MCC-DM1 demonstrates target-dependent killing of NHL cell lines in vitro. For HER2-high cells, MC-DM1-containing ADCs such as trastuzumab-MCC-DM1/T-DM1 show potent antiproliferative effects with significantly superior in vitro cytotoxicity compared to naked trastuzumab in SK-BR-3 cells. MC-DM1-containing affibody-drug conjugates exhibit IC₅₀ values ranging from 0.6 to 33 nM against HER2-overexpressing cells.
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| ln Vivo |
MC-DM1-containing ADCs demonstrate potent antitumor activity in various xenograft models. Anti-CD79b-MCC-DM1 is equally effective at low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas. The trastuzumab-based ADC T-DM1 (Kadcyla®) is approved for HER2-positive metastatic breast cancer. In HER2-overexpressing xenograft models, a HER2-targeting MC-DM1 affibody-drug conjugate at 10.3 or 15.1 mg/kg once-weekly for four weeks leads to efficient tumor regression. In gastric cancer cells, T-DM1 inhibits microtubule polymerization, but the active metabolite Lys-MCC-DM1 accumulates significantly less in resistant cells.
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| Cell Assay |
Cell Viability and Cytotoxicity Assay: HER2-positive and HER2-negative breast cancer cells are seeded in 96-well plates and treated with various concentrations of trastuzumab-MCC-DM1, naked trastuzumab, or free DM1 for 72 hours. Cell viability is assessed by MTT assay, and cytotoxicity is evaluated by LDH release assay and apoptosis detection. Binding Affinity Analysis: Binding capacity of antibodies or ADCs to cell surface antigens is assessed by flow cytometry.
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| Animal Protocol |
Subcutaneous Xenograft Model: Tumor cells are implanted subcutaneously into immunodeficient mice. After tumor establishment, MC-DM1 ADC formulations are administered via intravenous or intraperitoneal injection, and tumor volumes and weights are measured periodically to evaluate antitumor efficacy.
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| ADME/Pharmacokinetics |
The pharmacokinetic profile of MC-DM1 is primarily studied in its antibody-conjugated form. In female tumor-bearing nude rats, the ADC clears with half-lives of 51–62 hours, with MC-DM1-related radioactivity showing minor tissue distribution and highest concentrations in the tumor. Uncleavable linker ADCs (MCC-DM1) clear slower than cleavable linker ADCs (approximately 18.0 vs. 59.4 mL/day/kg) in rats, with approximately 70-fold lower exposure of free DM1 in plasma. Excretion is mainly via feces (84.5%±3.12%), with minor urinary excretion (4.15%±0.462%). The primary detectable catabolite of MC-DM1 is Lys-MCC-DM1.
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| Toxicity/Toxicokinetics |
MC-DM1-containing ADCs exhibit improved safety profiles compared to cleavable linker ADCs. In rats, ADCs with uncleavable linkers (MCC-DM1) cause less hepatic and hematologic toxicity, likely due to decreased systemic release of free drug. In cynomolgus monkeys, MCC-DM1 ADCs show clinically tolerated and reversible elevations in liver enzymes, decreased platelet counts, and minimal to mild sciatic nerve degeneration. In preclinical studies, an MC-DM1-containing HER2-targeting affibody-drug conjugate causes weight loss at higher doses, suggesting proximity to the maximum tolerated dose.
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| References | |
| Additional Infomation |
MC-DM1 is one of the core payloads in antibody-drug conjugate technology. The ADC formed by conjugating it with trastuzumab via a non-cleavable MCC linker—ado-trastuzumab emtansine (T-DM1, brand name Kadcyla®)—received FDA approval in 2013 for the treatment of HER2-positive metastatic breast cancer. MC-DM1 conjugated to an anti-CD79b antibody has also been studied for the treatment of non-Hodgkin lymphoma in ADCs related to polatuzumab vedotin.
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| Molecular Formula |
C42H55CLN4O12
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|---|---|
| Molecular Weight |
843.358711481094
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| Exact Mass |
842.35
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| Elemental Analysis |
C, 59.82; H, 6.57; Cl, 4.20; N, 6.64; O, 22.76
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| CAS # |
1375089-56-7
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| PubChem CID |
76072941
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
59
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| Complexity |
1690
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| Defined Atom Stereocenter Count |
8
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| SMILES |
ClC1C(=CC2CC(C)=CC=C[C@H]([C@]3(C[C@@H]([C@@H](C)[C@H]4[C@](C)([C@H](CC(N(C)C=1C=2)=O)OC([C@H](C)N(C(CCCCCN1C(C=CC1=O)=O)=O)C)=O)O4)OC(N3)=O)O)OC)OC |c:7,9|
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| InChi Key |
GBPANNIQRLRII-RJPAQOSPSA-N
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| InChi Code |
InChI=1S/C42H55ClN4O12/c1-24-13-12-14-31(56-8)42(54)23-30(57-40(53)44-42)25(2)38-41(4,59-38)32(22-36(51)46(6)28-20-27(19-24)21-29(55-7)37(28)43)58-39(52)26(3)45(5)33(48)15-10-9-11-18-47-34(49)16-17-35(47)50/h12-14,16-17,20-21,25-26,30-32,38,54H,9-11,15,18-19,22-23H2,1-8H3,(H,44,53)/b14-12+,24-13+/t25-,26+,30+,31-,32+,38+,41+,42+/m1/s1
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| Chemical Name |
(14S,16S,32S,33S,2R,4S,10E,12E,14R)-86-chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl)-N-methyl-L-alaninate
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| Synonyms |
MC-DM1; MC DM1; MCDM1; Maytansine, N2′-deacetyl-N2′-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-; MC DM-1; 1375089-56-7; (14S,16S,32S,33S,2R,4S,10E,12E,14R)-86-Chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl)-N-methyl-L-alaninate; [(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-[6-(2,5-dioxopyrrol-1-yl)hexanoyl-methylamino]propanoate
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : 220 mg/mL (260.86 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (6.52 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 55.0 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 | 1.1857 mL | 5.9287 mL | 11.8573 mL | |
| 5 mM | 0.2371 mL | 1.1857 mL | 2.3715 mL | |
| 10 mM | 0.1186 mL | 0.5929 mL | 1.1857 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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