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| Targets |
The target of sulfo-SPDB-DM4 is 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. In ADC applications, the conjugate targets tumor cells via antibody-mediated recognition. The sulfo-SPDB linker enables intracellular payload release with enhanced solubility.
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| ln Vitro |
DM4, a structural homologue of maytansinoid, is a novel and powerful thiol-containing maytansinoid alkaloid. DM4 is a cytotoxic maytansinoid medication. It is used to connect maytansinoid alkaloids to antibodies via disulfide bonds. Maytansinoid alkaloids reduce tubulin polymerization and microtubule assembly while increasing microtubule instability, effectively suppressing microtubule dynamics, resulting in mitotic block and consequent apoptosis [1].
Sulfo-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 sulfonated SPDB linker improves solubility and stability compared to the non-sulfonated version. The conjugate demonstrates effective cell killing in ADC formats. Purity is typically >99%. |
| ln Vivo |
In vivo, sulfo-SPDB-DM4 demonstrates potent anti-tumor activity when used in ADC formats. The sulfonated linker enhances solubility and stability in circulation. The conjugate is designed for efficient delivery of the payload to tumor cells while minimizing systemic toxicity. The DM4 payload exerts its cytotoxic effects through tubulin inhibition following intracellular release. The sulfo-SPDB-DM4 system is studied for its potential to selectively target and kill tumor cells while minimizing off-target effects.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for sulfo-SPDB-DM4 typically involve assessing the linker-payload conjugate's stability and cleavage characteristics. The sulfo-SPDB linker is a cleavable disulfide-based linker with enhanced solubility due to the sulfonate group. Release kinetics are evaluated by incubating the conjugate with reducing agents 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 sulfo-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. The sulfonated linker's enhanced solubility may improve assay performance. Internalization studies confirm antibody-mediated uptake. IC50 values are determined from dose-response curves.
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| Animal Protocol |
In vivo animal studies for sulfo-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. The sulfonated linker's improved solubility may enhance PK properties. Endpoints include tumor volume, body weight, and survival.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of sulfo-SPDB-DM4 conjugates follow typical ADC PK profiles with enhanced solubility from the sulfonate group. Following intravenous administration, the conjugate shows biphasic elimination with stability in circulation. The sulfo-SPDB linker provides controlled release characteristics through disulfide reduction. PK parameters are determined via ELISA and LC-MS/MS. The sulfonated modification may improve aqueous solubility and reduce aggregation.
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| Toxicity/Toxicokinetics |
Toxicological data for sulfo-SPDB-DM4 is characteristic of maytansine-based ADC linker-payload constructs. DM4 is a potent cytotoxic agent, and appropriate safety precautions should be observed. The sulfo-SPDB linker is designed to minimize systemic toxicity through targeted delivery. Standard safety precautions including PPE and fume hood use should be followed. Comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
sulfo-SPDB-DM4 (CAS# 1626359-59-8) is a research-grade drug-linker conjugate for ADC development. It is not approved for clinical use. The sulfo-SPDB linker is a cleavable disulfide-based linker with enhanced solubility due to sulfonation. DM4 is a maytansine derivative and potent microtubule inhibitor. This conjugate is studied for its potential to selectively target and kill tumor cells while minimizing off-target effects. The compound is for research use only.
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| Molecular Formula |
C46H63CLN4O17S3
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|---|---|
| Molecular Weight |
1075.6570
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| Exact Mass |
1074.303
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| CAS # |
1626359-59-8
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| PubChem CID |
146048619
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| Appearance |
White to yellow solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
71
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| Complexity |
2180
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| Defined Atom Stereocenter Count |
8
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| SMILES |
ClC1C(=C([H])C2C([H])([H])C(C([H])([H])[H])=C([H])C([H])=C([H])C([H])(C3(C([H])([H])C([H])(C([H])(C([H])([H])[H])C4([H])C(C([H])([H])[H])(C([H])(C([H])([H])C(N(C([H])([H])[H])C=1C=2[H])=O)OC(C([H])(C([H])([H])[H])N(C(C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])SSC([H])([H])C([H])([H])C([H])(C(=O)ON1C(C([H])([H])C([H])([H])C1=O)=O)S(=O)(=O)O[H])=O)C([H])([H])[H])=O)O4)OC(N3[H])=O)O[H])OC([H])([H])[H])OC([H])([H])[H]
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| InChi Key |
ACJLJPQSHWOFQD-KRXLDPNFSA-N
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| InChi Code |
InChI=1S/C46H63ClN4O17S3/c1-25-12-11-13-33(64-10)46(59)24-31(65-43(58)48-46)26(2)40-45(6,67-40)34(23-38(55)50(8)29-21-28(20-25)22-30(63-9)39(29)47)66-41(56)27(3)49(7)35(52)16-18-44(4,5)70-69-19-17-32(71(60,61)62)42(57)68-51-36(53)14-15-37(51)54/h11-13,21-22,26-27,31-34,40,59H,14-20,23-24H2,1-10H3,(H,48,58)(H,60,61,62)/b13-11-,25-12-/t26-,27+,31+,32?,33-,34+,40+,45+,46+/m1/s1
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| Chemical Name |
4-[[5-[[(2S)-1-[[(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]oxy]-1-oxopropan-2-yl]-methylamino]-2-methyl-5-oxopentan-2-yl]disulfanyl]-1-(2,5-dioxopyrrolidin-1-yl)oxy-1-oxobutane-2-sulfonic acid
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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 : ~50 mg/mL (~46.48 mM)
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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 | 0.9297 mL | 4.6483 mL | 9.2966 mL | |
| 5 mM | 0.1859 mL | 0.9297 mL | 1.8593 mL | |
| 10 mM | 0.0930 mL | 0.4648 mL | 0.9297 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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