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Purity: ≥98%
| Targets |
Maytansinoid DM4 targets tubulin, the protein that forms microtubules. Microtubules are essential for cell division, intracellular transport, and maintaining cell shape. DM4 binds to tubulin and inhibits its polymerization, thereby disrupting the formation of the mitotic spindle. This leads to cell cycle arrest at the G2/M phase and ultimately triggers apoptosis. Its high potency makes it an effective cytotoxic payload for ADCs.
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| ln Vitro |
A novel thiol-containing powerful maytansinoid is DM4, a structural analogue of maytansine. A cytotoxic maytansinoid medication is DM4. It is synthesized to form disulfide bonds between maytansinoids and antibodies. Maytansinoids potently suppress microtubule dynamics, causing a mitotic block and consequent apoptotic cell death. They do this by inhibiting tubulin polymerization and microtubule assembly and by enhancing microtubule destabilization[1].
In vitro, Maytansinoid DM4 is a highly potent inhibitor of cell proliferation. It has IC50 values in the sub-nanomolar to picomolar range against various cancer cell lines. Its activity is characterized by its ability to cause cell cycle arrest and induce apoptosis. As an ADC payload, its potency is a key feature, as it allows for the selective killing of cancer cells at low concentrations. |
| ln Vivo |
In vivo, Maytansinoid DM4 is not administered as a free drug due to its high systemic toxicity. Instead, it is used as a payload in ADCs. In this context, the ADC delivers DM4 specifically to tumor cells, where it is released to exert its cytotoxic effects. This targeted delivery significantly improves the therapeutic index of DM4.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies are not applicable to Maytansinoid DM4, as it targets tubulin, not an enzyme or receptor. Its activity is assessed in cell-based assays measuring its effects on microtubule dynamics and cell proliferation.
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| Cell Assay |
In vitro cellular assays for Maytansinoid DM4 involve treating cancer cell lines with the compound. Key readouts include cell viability (MTT or CellTiter-Glo assays), cell cycle analysis (propidium iodide staining), and apoptosis (Annexin V/PI staining). Its effects on tubulin polymerization can be assessed using immunofluorescence microscopy.
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| Animal Protocol |
In vivo animal studies for Maytansinoid DM4 are conducted using ADCs that incorporate DM4 as the payload. These studies are performed in xenograft mouse models. Tumor-bearing mice are treated with the ADC, and endpoints include tumor growth inhibition, survival, and pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Maytansinoid DM4 are characterized in the context of ADCs. It has a molecular weight of 780.33 g/mol and a formula of C39H56ClN5O10S. Its high potency and hydrophobic nature make it suitable for conjugation to antibodies.
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| Toxicity/Toxicokinetics |
Maytansinoid DM4 is a highly potent cytotoxic agent and is classified as a hazardous compound. It is too toxic for systemic administration as a free drug. Its toxicity is mitigated by its use in ADCs, which deliver it specifically to tumor cells.
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| References |
[2]. Schönfeld K, Zuber C, Pinkas J, Häder T, Bernöster K, Uherek C. Indatuximab ravtansine (BT062) combination treatment in multiple myeloma: pre-clinical studies. J Hematol Oncol. 2017 Jan 11;10(1):13. doi: 10.1186/s13045-016-0380-0. PubMed PMID: 28077160; PubMed Central PMCID: PMC5225632.
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| Additional Infomation |
Ravtansine is an organic molecular entity. Ravtansine is a tubulin-binding maytansine compound. It binds to the maytansine binding site on tubulin, thereby disrupting the assembly/disassembly dynamics of microtubules and inhibiting mitosis. It is an anza macrolide compound isolated from the East African shrub Maytansine. See also: Maytansine (note moved to).
Maytansinoid DM4 is a potent cytotoxic payload used in ADCs. Its CAS number is 796073-69-3. It is a derivative of maytansine. It is a key component of several ADCs in clinical development for the treatment of cancer. It is not an approved drug on its own. |
| Molecular Formula |
C38H54N3O10SCL
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|---|---|
| Molecular Weight |
780.371
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| Exact Mass |
779.322
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| Elemental Analysis |
C, 58.49; H, 6.98; Cl, 4.54; N, 5.38; O, 20.50; S, 4.11
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| CAS # |
796073-69-3
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| Related CAS # |
DM4-d6
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| PubChem CID |
11686439
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| Appearance |
White to light yellow solid powder
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| Density |
1.29±0.1 g/cm3
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| Boiling Point |
943.2±65.0 °C
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| Melting Point |
185-187 °C (decomp)
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| LogP |
5.396
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
53
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| Complexity |
1430
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| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@]12[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCC(S)(C)C)CC(=O)N(C)C3C(=C(C=C(C=3)CC(C)=CC=C[C@@H](OC)[C@@]3(NC(O[C@@H](C3)[C@@H](C)[C@@H]1O2)=O)O)OC)Cl |c:32,34,&1:1,2,6,35,38,42,44,46|
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| InChi Key |
JFCFGYGEYRIEBE-YVLHJLIDSA-N
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| InChi Code |
InChI=1S/C38H54ClN3O10S/c1-21-12-11-13-28(49-10)38(47)20-27(50-35(46)40-38)22(2)33-37(6,52-33)29(51-34(45)23(3)41(7)30(43)14-15-36(4,5)53)19-31(44)42(8)25-17-24(16-21)18-26(48-9)32(25)39/h11-13,17-18,22-23,27-29,33,47,53H,14-16,19-20H2,1-10H3,(H,40,46)/b13-11+,21-12+/t22-,23+,27+,28-,29+,33+,37+,38+/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-(4-mercapto-4-methylpentanoyl)-N-methyl-L-alaninate
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| Synonyms |
Maytansinoid DM4; DM4, Ravtansine, Soravtansine
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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 (~128.14 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.20 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: 2.5 mg/mL (3.20 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 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: ≥ 2.5 mg/mL (3.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+ 40% PEG300+ 5% Tween-80+ 45% saline: ≥ 2.5 mg/mL (3.20 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2814 mL | 6.4072 mL | 12.8144 mL | |
| 5 mM | 0.2563 mL | 1.2814 mL | 2.5629 mL | |
| 10 mM | 0.1281 mL | 0.6407 mL | 1.2814 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03552471 | Active, not recruiting | Other: Laboratory Biomarker Analysis Biological: Mirvetuximab Soravtansine |
BRCA1 Gene Mutation BRCA2 Gene Mutation Folate Receptor Alpha Positive |
Ohio State University Comprehensive Cancer Center | July 12, 2018 | Phase 1 |
| NCT03126630 | Active, not recruiting | Biological: Anetumab Ravtansine Other: Laboratory Biomarker Analysis |
Pleural Malignant Mesothelioma | National Cancer Institute (NCI) | October 4, 2018 | Phase 1 Phase 2 |
| NCT03045393 | Withdrawn | Drug: Mirvetuximab Soravtansine | Breast Cancer Triple Negative | Duke University | April 17, 2017 | Phase 1 |
| NCT03106077 | Completed | Biological: Mirvetuximab Soravtansine |
M.D. Anderson Cancer Center | Duke University | June 5, 2017 | Phase 2 |
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