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| 5mg |
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| Targets |
This compound is a linker, not a drug, and its "target" is a specific thiol group on a cysteine residue of an antibody for initial conjugation. Its cleavable nature allows it to be degraded (likely by cathepsins in the lysosome) to release the attached cytotoxic payload after ADC internalization.
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| ln Vitro |
This molecule is not a drug; its activity is chemical. It is designed to be stable in circulation (in the blood) but undergo selective cleavage once the ADC is internalized into the target cancer cell and trafficked to the lysosome. The hydrophilic nature (PEG and bis(deoxyglucitol)) helps to maintain the overall solubility of the ADC and prevent aggregation.
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| ln Vivo |
Specific in vivo activity data for this linker alone is not provided. The in vivo efficacy is achieved when it is part of a fully assembled ADC. The linker ensures that the toxic payload is delivered specifically to the tumor, improving the therapeutic window by minimizing systemic toxicity. Studies would measure the anti-tumor activity of the complete ADC in xenograft models.
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| Enzyme Assay |
A non-cellular assay to validate the linker is a conjugation efficiency study. Purified antibody (e.g., trastuzumab) is first partially reduced to generate free thiols. Mal-EGGGG-PEG8-amide-bis(deoxyglucitol) is then added at a defined molar ratio. The reaction mixture is analyzed by Hydrophobic Interaction Chromatography (HIC) or Liquid Chromatography-Mass Spectrometry (LC-MS) to determine the drug-to-antibody ratio (DAR), which is the average number of linker-payload molecules attached per antibody.
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| Cell Assay |
The linker itself is not used in a cell viability assay. Its utility is assessed after it is conjugated to a cytotoxic payload (e.g., a tubulin inhibitor like MMAE) to form a complete ADC. The in vitro potency of this ADC is then tested on target-positive cancer cells (e.g., HER2-positive SK-BR-3 cells) and target-negative cells. Cells are incubated with serial dilutions of the ADC for 72-96 hours. Cell viability is then measured using a standard assay like CellTiter-Glo. A high DAR and a wide differential in IC₅0 between the two cell lines indicate a high-quality linker.
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| Animal Protocol |
In vivo studies are performed on the complete ADC, not the linker alone. A typical protocol involves using a mouse xenograft model with a human tumor cell line. Once tumors reach a certain size (e.g., 150 mm3), the ADC is administered intravenously, often at multiple dose levels. Tumor volume is measured with calipers twice a week, and the primary endpoint is often tumor growth inhibition (TGI) or tumor regression. Body weight is monitored as a measure of systemic toxicity.
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| ADME/Pharmacokinetics |
The properties of the linker directly affect the PK of the ADC. The hydrophilic PEG8 and bis(deoxyglucitol) groups are designed to reduce the ADC's clearance rate and improve its exposure, leading to a longer serum half-life compared to more hydrophobic linkers. The stability of the linker in plasma prevents premature release of the payload.
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| Toxicity/Toxicokinetics |
No toxicity information for the linker alone is provided. The toxicity of the final ADC is largely driven by the cytotoxic payload. A well-designed ADC with a stable cleavable linker will have a significantly higher maximum tolerated dose (MTD) than the payload alone because the payload is only released at the tumor site. The primary toxicity is often manageable and target-mediated.
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| Additional Infomation |
This is a next-generation ADC linker. It is "cleavable" (likely an enzyme-cleavable dipeptide or tetrapeptide linker) and designed to release its payload specifically inside cancer cells. The use of multiple sugar (bis-deoxyglucitol) and PEG groups is an advanced strategy to increase hydrophilicity and prevent drug aggregation, a common challenge in ADC development. This compound is a research tool.
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| Molecular Formula |
C55H94N10O31
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|---|---|
| Molecular Weight |
1391.38327741623
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| Exact Mass |
1390.608
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| CAS # |
2360920-01-8
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| PubChem CID |
168510638
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| Appearance |
White to off-white solid powder
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| LogP |
-13.8
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| Hydrogen Bond Donor Count |
20
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| Hydrogen Bond Acceptor Count |
31
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| Rotatable Bond Count |
59
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| Heavy Atom Count |
96
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| Complexity |
2370
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| Defined Atom Stereocenter Count |
10
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| SMILES |
O[C@@H]([C@@H]([C@@H](CO)O)O)[C@H](CNC([C@H](CCC(NC[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O)=O)NC(CCOCCOCCOCCOCCOCCOCCOCCOCCNC(CNC(CNC(CNC(CNC([C@H](CCC(=O)O)NC(CN1C(C=CC1=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)O
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| InChi Key |
VSCPNQGDWPYXJQ-QPEMRJNGSA-N
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| InChi Code |
InChI=1S/C55H94N10O31/c66-32-38(70)52(85)50(83)36(68)25-57-40(72)3-1-34(54(87)61-26-37(69)51(84)53(86)39(71)33-67)63-41(73)7-9-89-11-13-91-15-17-93-19-21-95-23-24-96-22-20-94-18-16-92-14-12-90-10-8-56-42(74)27-58-43(75)28-59-44(76)29-60-45(77)30-62-55(88)35(2-6-49(81)82)64-46(78)31-65-47(79)4-5-48(65)80/h4-5,34-39,50-53,66-71,83-86H,1-3,6-33H2,(H,56,74)(H,57,72)(H,58,75)(H,59,76)(H,60,77)(H,61,87)(H,62,88)(H,63,73)(H,64,78)(H,81,82)/t34-,35-,36-,37-,38+,39+,50+,51+,52+,53+/m0/s1
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| Chemical Name |
(4S)-5-[[2-[[2-[[2-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[3-[[(2S)-1,5-dioxo-1,5-bis[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentan-2-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-4-[[2-(2,5-dioxopyrrol-1-yl)acetyl]amino]-5-oxopentanoic 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) |
H2O : 100 mg/mL (71.87 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 | 0.7187 mL | 3.5936 mL | 7.1871 mL | |
| 5 mM | 0.1437 mL | 0.7187 mL | 1.4374 mL | |
| 10 mM | 0.0719 mL | 0.3594 mL | 0.7187 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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