| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Mc-VC-PAB-SN38 consists of a cleavable ADC linker (Mc-VC-PAB) and the DNA topoisomerase I inhibitor SN38. SN38 targets DNA topoisomerase I, an enzyme that relieves torsional stress during DNA replication and transcription. By inhibiting topoisomerase I, SN38 induces DNA damage and apoptosis in cancer cells. The Mc-VC-PAB linker is cleaved by cathepsin B, a lysosomal enzyme that is overexpressed in many tumors, allowing for selective release of SN38 at the target site. The compound has a molecular formula of C51H58N8O13 and a molecular weight of 991.05 g/mol.
|
|---|---|
| ln Vitro |
ADC is made up of an antibody and an ADC linker that connects the ADC cytotoxin [1].
In vitro, Mc-VC-PAB-SN38 is used as a drug-linker conjugate for the synthesis of ADCs. The maleimide group (Mc) reacts with sulfhydryl groups on antibodies to form stable thioether bonds. The valine-citrulline (VC) dipeptide is specifically cleaved by cathepsin B, which is overexpressed in lysosomes of tumor cells. Upon cleavage, the PAB spacer undergoes spontaneous elimination, releasing SN38. The released SN38 inhibits DNA topoisomerase I, leading to DNA damage and apoptosis. ADCs are comprised of an antibody to which is attached an ADC cytotoxin through an ADC linker. |
| ln Vivo |
No detailed in vivo activity data for Mc-VC-PAB-SN38 has been published in the available literature. The compound is a research tool used primarily for the synthesis of ADCs. Its in vivo activity would depend on the specific antibody to which it is conjugated. The cleavable nature of the linker allows for the release of SN38 at the target site. Mc-VC-PAB-SN38-based ADCs have been evaluated in preclinical and clinical studies for various cancers.
|
| Enzyme Assay |
The conjugation of Mc-VC-PAB-SN38 to antibodies can be assessed using various analytical techniques. In a typical conjugation reaction, the antibody is first reduced to generate free sulfhydryl groups. Mc-VC-PAB-SN38 is then added to the reduced antibody at a defined molar ratio. The reaction is incubated at room temperature. The degree of conjugation is assessed by MALDI-TOF mass spectrometry, hydrophobic interaction chromatography (HIC), or SDS-PAGE. The purity of the conjugate is assessed by size exclusion chromatography (SEC).
|
| Cell Assay |
The cellular activity of Mc-VC-PAB-SN38 conjugates is assessed in cell-based assays. The ADC is added to target cells expressing the appropriate antigen. Cell viability is measured using MTT or CellTiter-Glo assays. The specificity of the conjugate for target cells is assessed by comparing activity against antigen-positive and antigen-negative cell lines. The mechanism of cell killing is confirmed by assessing DNA damage and apoptosis.
|
| Animal Protocol |
Mc-VC-PAB-SN38 conjugates have been evaluated in animal models using the specific ADC to which they are conjugated. Typical studies involve xenograft models in immunodeficient mice. The ADC is administered at various doses and schedules. Tumor volumes are measured twice weekly. Pharmacokinetic and toxicokinetic parameters are assessed.
|
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data for Mc-VC-PAB-SN38 has been published in the available literature. The compound has a molecular weight of 991.05 g/mol and a molecular formula of C51H58N8O13. The compound has a purity of >98%. The pharmacokinetic properties of Mc-VC-PAB-SN38 conjugates would depend on the specific antibody. Further studies would be needed to characterize the pharmacokinetic properties of Mc-VC-PAB-SN38 and its conjugates.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data for Mc-VC-PAB-SN38 has been published in the available literature. As a research compound used in ADC synthesis, Mc-VC-PAB-SN38 is not intended for direct therapeutic use. The toxicity of Mc-VC-PAB-SN38 conjugates would depend on the specific antibody and the released SN38. SN38 is a potent topoisomerase I inhibitor with known toxicities including myelosuppression and gastrointestinal effects.
|
| References | |
| Additional Infomation |
Mc-VC-PAB-SN38 (CAS#: 1801838-28-7) is a drug-linker conjugate consisting of the cleavable Mc-VC-PAB linker and the DNA topoisomerase I inhibitor SN38. The compound is used in the synthesis of antibody-drug conjugates (ADCs) for targeted cancer therapy. The Mc-VC-PAB linker is cleaved by cathepsin B in the lysosome, releasing SN38. The compound has a molecular weight of 991.05 g/mol and a molecular formula of C51H58N8O13. It has a purity of >98%. Mc-VC-PAB-SN38 is a valuable tool for the development of targeted cancer therapies.
|
| Molecular Formula |
C51H58N8O13
|
|---|---|
| Molecular Weight |
991.05203294754
|
| Exact Mass |
990.412
|
| CAS # |
1801838-28-7
|
| PubChem CID |
146160908
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
23
|
| Heavy Atom Count |
72
|
| Complexity |
2190
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
O1C([C@](CC)(C2C=C3C4C(=C(CC)C5C=C(C=CC=5N=4)O)CN3C(C=2C1)=O)OC(=O)OCC1C=CC(=CC=1)NC([C@H](CCCNC(N)=O)NC([C@H](C(C)C)NC(CCCCCN1C(C=CC1=O)=O)=O)=O)=O)=O
|
| InChi Key |
CNDJKXYZKSJFNL-XLPKKHSNSA-N
|
| InChi Code |
InChI=1S/C51H58N8O13/c1-5-32-33-23-31(60)17-18-37(33)55-44-34(32)25-59-39(44)24-36-35(47(59)66)27-70-48(67)51(36,6-2)72-50(69)71-26-29-13-15-30(16-14-29)54-45(64)38(11-10-21-53-49(52)68)56-46(65)43(28(3)4)57-40(61)12-8-7-9-22-58-41(62)19-20-42(58)63/h13-20,23-24,28,38,43,60H,5-12,21-22,25-27H2,1-4H3,(H,54,64)(H,56,65)(H,57,61)(H3,52,53,68)/t38-,43-,51-/m0/s1
|
| Chemical Name |
[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl [(19S)-10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl] carbonate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 28.57 mg/mL (28.83 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.86 mg/mL (2.89 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 28.6 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0090 mL | 5.0452 mL | 10.0903 mL | |
| 5 mM | 0.2018 mL | 1.0090 mL | 2.0181 mL | |
| 10 mM | 0.1009 mL | 0.5045 mL | 1.0090 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
