| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| 25mg | |||
| Other Sizes |
| Targets |
Maytansinoids
SPDB-DM4 targets microtubules through the DM4 payload, which is a maytansine derivative that inhibits tubulin polymerization and disrupts microtubule dynamics. DM4 is a potent anti-tubulin agent that prevents cancer cell division by blocking mitosis. In ADC applications, the conjugate targets cancer cells via antibody-mediated recognition of tumor-associated antigens. The SPDB linker enables intracellular payload release. |
|---|---|
| ln Vitro |
SPDB-DM4 exhibits potent in vitro anti-tumor activity through the action of the DM4 payload. DM4 is a potent microtubule inhibitor that prevents cancer cell division. The conjugate demonstrates effective cell killing when incorporated into ADC constructs with appropriate targeting antibodies. The SPDB linker enables efficient intracellular release of the payload following antibody-mediated internalization.
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| ln Vivo |
In vivo, SPDB-DM4 demonstrates potent anti-tumor activity when used in ADC formats. The conjugate is designed for stability in circulation while enabling targeted payload delivery to tumors. The SPDB linker provides appropriate stability and release characteristics for effective in vivo performance. The DM4 payload exerts its cytotoxic effects through tubulin inhibition following intracellular release.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for SPDB-DM4 typically involve assessing the linker-payload conjugate's stability and cleavage characteristics. The SPDB linker is a cleavable disulfide-based linker that undergoes intracellular reduction to release the DM4 payload. Release kinetics are evaluated by incubating the conjugate with reducing agents such as DTT or glutathione, followed by HPLC or LC-MS analysis to quantify DM4 release. Tubulin binding assays confirm retained activity of the DM4 payload.
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| Cell Assay |
In vitro cellular assays for SPDB-DM4 ADC conjugates involve treating antigen-positive and antigen-negative cell lines with varying concentrations (typically 0.001-100 nM range) for 72-120 hours. Cell viability is assessed using standard assays such as MTT, CellTiter-Glo, or colony formation assays. Internalization studies using fluorescently labeled constructs confirm antibody-mediated uptake. IC50 values are determined from dose-response curves. Appropriate controls include naked antibody and free DM4 payload.
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| Animal Protocol |
In vivo animal studies for SPDB-DM4 ADC conjugates typically employ xenograft mouse models bearing human tumor cell lines. Tumor-bearing mice are administered the ADC via intravenous injection at various dose levels (typically 1-30 mg/kg) on schedules such as single dose or repeat dosing. Tumor growth inhibition is monitored over 2-4 weeks. Endpoints include tumor volume measurements, body weight monitoring, and survival analysis. Pharmacodynamic biomarkers may be assessed in tumor tissue.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SPDB-DM4 conjugates follow typical ADC PK profiles. Following intravenous administration, the conjugate shows biphasic elimination with stability in circulation. The SPDB linker provides controlled release characteristics through disulfide reduction. PK parameters including clearance, volume of distribution, and half-life are determined via ELISA for total antibody and conjugated antibody, and LC-MS/MS for free DM4 payload. Stability in plasma is assessed.
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| Toxicity/Toxicokinetics |
Toxicological data for SPDB-DM4 is characteristic of maytansine-based ADC linker-payload constructs. DM4 is a potent cytotoxic agent, and appropriate safety precautions should be observed during handling including PPE and work in a fume hood. The SPDB linker is designed for targeted delivery to minimize systemic toxicity. Comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
SPDB-DM4 (CAS# 1626359-62-3) is a research-grade drug-linker conjugate for ADC development. It is not approved for clinical use. The SPDB linker is a cleavable disulfide-based linker system used in ADC research. DM4 is a maytansine derivative that is a potent microtubule inhibitor. This conjugate enables research into maytansine-based ADC therapeutics. The compound is typically stored at -20degC. It is for research use only and not for therapeutic applications.
|
| Molecular Formula |
H5MBPS
|
|---|---|
| Molecular Weight |
78.8895
|
| Exact Mass |
994.347
|
| CAS # |
1626359-62-3
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| PubChem CID |
162393097
|
| Appearance |
White to light yellow solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
16
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
67
|
| Complexity |
1910
|
| Defined Atom Stereocenter Count |
7
|
| SMILES |
C[C@]1([C@H](CC(N(C(C=C2C=C3OC)=C3Cl)C)=O)OC([C@H](C)N(C)C(CCC(C)(C)SSCCCC(ON(C4=O)C(CC4)=O)=O)=O)=O)[C@H]([C@@H]([C@](OC5=O)([H])C[C@]([C@](/C=C/C=C(C)/C2)([H])OC)(N5)O)C)O1
|
| InChi Key |
LAVNQRWLLQGEIB-UHAQQUCISA-N
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| InChi Code |
InChI=1S/C46H63ClN4O14S2/c1-26-13-11-14-33(61-10)46(59)25-32(62-43(58)48-46)27(2)41-45(6,64-41)34(24-38(55)50(8)30-22-29(21-26)23-31(60-9)40(30)47)63-42(57)28(3)49(7)35(52)18-19-44(4,5)67-66-20-12-15-39(56)65-51-36(53)16-17-37(51)54/h11,13-14,22-23,27-28,32-34,41,59H,12,15-21,24-25H2,1-10H3,(H,48,58)/t27-,28+,32+,33-,34?,41+,45+,46+/m1/s1
|
| Chemical Name |
(2,5-dioxopyrrolidin-1-yl) 4-[[5-[[(2S)-1-[[(1S,2R,3S,5S,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]oxy]-1-oxopropan-2-yl]-methylamino]-2-methyl-5-oxopentan-2-yl]disulfanyl]butanoate
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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 : ≥ 300 mg/mL (~301.33 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.51 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 (2.51 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 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 (2.51 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 (2.51 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 12.6759 mL | 63.3794 mL | 126.7588 mL | |
| 5 mM | 2.5352 mL | 12.6759 mL | 25.3518 mL | |
| 10 mM | 1.2676 mL | 6.3379 mL | 12.6759 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 |
| NCT03106077 | Completed | Biological: Mirvetuximab Soravtansine |
Anatomic Stage II Breast Cancer AJCC v8 | M.D. Anderson Cancer Center | June 5, 2017 | Phase 2 |
| NCT03552471 | Active, not recruiting | Other: Laboratory Biomarker Analysis Biological: Mirvetuximab Soravtansine |
BRCA1 Gene Mutation | Ohio State University Comprehensive Cancer Center | July 12, 2018 | Phase 1 |
| NCT02996825 | Active, not recruiting | Drug: Gemcitabine Drug: Gemcitabine Hydrochloride |
Recurrent Breast Carcinoma | City of Hope Medical Center | March 22, 2017 | Phase 1 |
| NCT00674947 | Completed | Drug: BIIB015 | Solid Tumors | Biogen | June 2008 | Phase 1 |
| NCT05703555 | Not yet recruiting | ravtansine | Metastatic Lung Cancer | Erasmus Medical Center | February 2023 | Phase 2 |
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