| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
The maytansinoid payload of DM-21 targets tubulin, binding to the vinca alkaloid binding site on beta-tubulin, thereby inhibiting microtubule polymerization. This disruption of the mitotic spindle leads to G2/M cell cycle arrest and subsequent apoptosis in dividing cells. The targeted delivery of the payload is mediated by the antibody component (e.g., anti-ADAM9) to which DM-21 is conjugated, enabling selective delivery to tumor cells.
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|---|---|
| ln Vitro |
The ADC is made up of a preamplifier, to which the ADC input connects the ADC cytotoxic.
DM-21 contains a maytansinoid payload, a class of potent microtubule-targeting agents that inhibit tubulin polymerization with IC50 values in the sub-nanomolar to low nanomolar range for cancer cell lines. The stable tripeptide linker is designed to be cleaved within target cells, releasing the active payload. When conjugated to an antibody, the resulting ADC exhibits antigen-dependent cytotoxicity, selectively killing target-expressing cancer cells while sparing non-target cells through the bystander effect. |
| ln Vivo |
The in vivo activity of DM-21 is determined by the complete ADC construct to which it is conjugated, rather than the linker-payload alone. When conjugated to an anti-ADAM9 antibody (IMGC936), the resulting ADC shows anti-tumor efficacy in mouse xenograft models of ADAM9-positive cancers, including non-small cell lung cancer, gastric cancer, and pancreatic cancer. The ADC is administered intravenously at doses of 1-10 mg/kg every 1-2 weeks, with observed tumor growth inhibition and regression at well-tolerated doses.
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| Enzyme Assay |
DM-21 is a linker-payload conjugate and is not used directly in enzyme/receptor binding assays. The conjugation efficiency is assessed by characterizing the drug-to-antibody ratio (DAR) of the final ADC using hydrophobic interaction chromatography (HIC) or liquid chromatography-mass spectrometry (LC-MS). The release of the payload from the linker in the presence of cathepsin B can be assessed in a cell-free system by incubating DM-21 with recombinant human cathepsin B and quantifying released maytansinoid by LC-MS.
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| Cell Assay |
Cellular activity is assessed using antigen-positive and antigen-negative cancer cells. The complete ADC (e.g., IMGC936, DM-21 conjugated to anti-ADAM9 antibody) is added to cells at varying concentrations (0.001-100 nM) for 72-120 hours. Viability is measured using CellTiter-Glo or MTT assays to calculate EC50 values. For bystander effect analysis, co-cultures of antigen-positive and antigen-negative cells are used to assess killing of non-target cells resulting from payload release and diffusion.
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| Animal Protocol |
In vivo efficacy is typically evaluated using a mouse xenograft model of ADAM9-positive cancer (e.g., lung, gastric, pancreatic). Female immunodeficient mice are injected subcutaneously with cancer cells. Once tumors reach ~150-200 mm3, mice are randomized and treated intravenously with the complete ADC (e.g., IMGC936) at doses of 1, 3, or 10 mg/kg once weekly for 2-3 weeks. Tumor volume is measured by calipers twice weekly, and serum levels of the ADC are measured by ELISA.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic parameters for DM-21 are not applicable, as it is not administered directly. Instead, the PK of the complete ADC (antibody + DM-21) is governed by the antibody component, typically exhibiting a long half-life (days), low clearance, and limited volume of distribution. The stable tripeptide linker is designed to maintain stability in circulation to prevent premature payload release, with the linker being cleaved inside target cells by lysosomal proteases.
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| Toxicity/Toxicokinetics |
DM-21 contains a maytansinoid payload, which is a potent cytotoxic agent; free maytansinoids are highly toxic and can cause severe myelosuppression, neuropathy, and gastrointestinal toxicity. However, when conjugated as part of an ADC, the payload is delivered specifically to tumor cells, significantly reducing systemic toxicity. The safety profile of the final ADC (e.g., IMGC936) is determined in preclinical animal studies and, if progressed, in clinical trials.
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| References | |
| Additional Infomation |
DM-21 is a research-grade ADC linker-payload conjugate, not a therapeutic agent on its own. It is used to construct next-generation ADCs with stable, cleavable tripeptide linkers designed to improve the therapeutic index compared to first-generation ADCs. The tripeptide linker is designed for cathepsin B-mediated cleavage, a key advantage for efficient payload release in target cells. As of the latest updates, the compound has not been approved for clinical use and is exclusively available for research purposes.
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| Molecular Formula |
C58H83CLN8O16S
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|---|---|
| Molecular Weight |
1215.84
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| Exact Mass |
1214.533
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| CAS # |
2243689-80-5
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| PubChem CID |
163342336
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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 |
6
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
26
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| Heavy Atom Count |
84
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| Complexity |
2470
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| Defined Atom Stereocenter Count |
11
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| SMILES |
C[C@]12[C@]([H])(CC(N(C3=C(C(OC)=CC(CC(C)=CC=C[C@@]([H])(OC)[C@@]4(NC(=O)O[C@@]([H])(C4)[C@@H](C)[C@@H]1O2)O)=C3)Cl)C)=O)OC(=O)[C@H](C)N(C)C(=O)CCCCCSCNC(=O)[C@H](C)NC(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)CCCCCN1C(C=CC1=O)=O |t:16,18,&1:1,2,20,24,29,32,34,44,60,65,70|
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| InChi Key |
SJIJPSFCGJDQNG-ZPKZLEQESA-N
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| InChi Code |
InChI=1S/C58H83ClN8O16S/c1-33-19-18-20-43(80-11)58(78)31-42(81-56(77)64-58)34(2)51-57(7,83-51)44(30-49(72)66(9)40-28-39(27-33)29-41(79-10)50(40)59)82-55(76)38(6)65(8)46(69)22-15-13-17-26-84-32-60-52(73)35(3)62-54(75)37(5)63-53(74)36(4)61-45(68)21-14-12-16-25-67-47(70)23-24-48(67)71/h18-20,23-24,28-29,34-38,42-44,51,78H,12-17,21-22,25-27,30-32H2,1-11H3,(H,60,73)(H,61,68)(H,62,75)(H,63,74)(H,64,77)/b20-18-,33-19-/t34-,35+,36+,37-,38+,42+,43-,44+,51+,57+,58+/m1/s1
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| Chemical Name |
[(1S,2R,3S,5S,6S,16Z,18Z,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-[[[(2S)-2-[[(2R)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]propanoyl]amino]propanoyl]amino]propanoyl]amino]methylsulfanyl]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 |
| 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 (~82.25 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (0.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (0.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (0.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8225 mL | 4.1124 mL | 8.2248 mL | |
| 5 mM | 0.1645 mL | 0.8225 mL | 1.6450 mL | |
| 10 mM | 0.0822 mL | 0.4112 mL | 0.8225 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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