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| Targets |
MCC itself has no pharmacological target. However, MCC-based ADCs target specific antigens, e.g., trastuzumab-MCC-DM1 targets HER2. Other examples include anti-CD22-MCC-DM1 for NHL and anti-CD79b-MCC-DM1. Targeting specificity is conferred by the antibody component, while MCC links the antibody to the cytotoxic payload.
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| ln Vitro |
Antibody-drug conjugates (ADCs) are strong cytotoxic medications that can selectively target cancerous cells because they are chemically bound to antibodies. In vitro, anti-CD22-MCC-DM1 exhibits broad efficacy against various NHL cell lines [1].
MCC alone has no activity. MCC-based ADCs show potent in vitro cytotoxicity against antigen-positive cancer cells. Anti-CD22-MCC-DM1 is effective against NHL B-cell lines. T-DM1 shows EC50 of 0.028 microg/mL in SK-BR-3 and ~2 microg/mL in BT-474 cells. It induces caspase-3/7 activation and inhibits cell proliferation in HER2-positive lines. |
| ln Vivo |
MCC-based ADCs demonstrate in vivo antitumor activity in xenograft models. Trastuzumab-MCC-DM1 shows superior activity over unconjugated trastuzumab. Anti-CD30-MCC-DM1 induces regression in Karpas 299, HH, and L428 models. Serum concentrations remain elevated; toxicity is negligible compared to free DM1 or reducible-linker ADCs. The non-cleavable linker contributes to reduced off-target toxicity.
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| Enzyme Assay |
As a linker, MCC has no receptor binding assays. Conjugation efficiency is assessed by SEC, HIC, or LC-MS to determine DAR. Stability is evaluated by incubating ADC in plasma or buffer and monitoring free payload release via LC-MS/MS. The maleimide group reacts with thiols via Michael addition to form stable thioether bonds, which are characterized by standard bioconjugation methods.
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| Cell Assay |
Cells (antigen-positive and -negative) are cultured with ADC for 72 hours. Viability is measured by MTT or ATP-luminescence. For T-DM1, LDH release and caspase-3/7 activation assays are used. IC50/EC50 values are calculated from dose-response curves. Selectivity is confirmed by comparing activity between antigen-positive and negative cells. Additional assays include cell cycle analysis and tubulin polymerization inhibition.
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| Animal Protocol |
Immunocompromised mice bearing subcutaneous xenografts are treated with ADC via IV injection at varying doses. Tumor volumes are measured over time. PK studies involve blood collection at multiple time points; ADC and catabolite concentrations are measured by LC-MS/MS or ELISA. Toxicity is assessed by body weight, clinical signs, and histopathology. Typical dose for T-DM1 in mice is 3 mg/kg.
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| ADME/Pharmacokinetics |
MCC-based ADCs exhibit antibody-like PK with long half-life and low clearance. T-DM1 shows elevated serum concentrations in rats. The non-cleavable MCC linker provides high plasma stability, limiting free DM1 release. Upon internalization, lysosomal degradation releases the active catabolite Lys-MCC-DM1, which is not metabolized by P450. The linker prevents premature drug release, contributing to favorable PK.
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| Toxicity/Toxicokinetics |
MCC-based ADCs show favorable toxicity profiles. In rats, T-DM1 toxicity is negligible compared to free DM1 or reducible-linker ADCs. Non-cleavable linker reduces systemic toxicity. However, liver toxicity has been observed with some MCC-DM1 ADCs. The charged catabolite Lys-MCC-DM1 does not readily cross membranes, limiting bystander effects and off-target toxicity. Generally better tolerated than cleavable counterparts.
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| References |
[1]. Polson AG, et al. Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma. Leukemia. 2010;24(9):1566-1573.
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| Additional Infomation |
MCC is used in T-DM1 (Kadcyla®), the first FDA-approved ADC for solid tumors (HER2+ breast cancer). T-DM1 binds HER2, internalizes, and releases Lys-MCC-DM1 to inhibit microtubule polymerization, causing cell cycle arrest and apoptosis. Other MCC-based ADCs include anti-CD22-MCC-DM1 and anti-CD79b-MCC-DM1. Clinical development continues, with B003 (anti-HER2-MCC-DM1) in Phase 1 trials.
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| Molecular Formula |
C12H16N2O3
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|---|---|
| Molecular Weight |
236.267043113708
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| Exact Mass |
236.116
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| CAS # |
104676-09-7
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| PubChem CID |
66787227
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| Appearance |
Light yellow to brown solid powder
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| LogP |
-0.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
363
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(CCC1CN2C(=O)C=CC2=O)C(=O)N
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| InChi Key |
IBLSXJXHUXUHIM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H16N2O3/c13-12(17)9-3-1-8(2-4-9)7-14-10(15)5-6-11(14)16/h5-6,8-9H,1-4,7H2,(H2,13,17)
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| Chemical Name |
4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2324 mL | 21.1622 mL | 42.3245 mL | |
| 5 mM | 0.8465 mL | 4.2324 mL | 8.4649 mL | |
| 10 mM | 0.4232 mL | 2.1162 mL | 4.2324 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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