| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The target of MC-VC-PABC-DNA31 is RNA polymerase, which is inhibited by the DNA31 payload. RNA polymerase is a critical enzyme for transcription, and its inhibition leads to disruption of RNA synthesis and ultimately cell death. In the context of ADC applications, the conjugate targets cancer cells via antibody-mediated recognition of tumor-associated antigens. The MC-VC-PABC linker enables selective intracellular payload release.
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|---|---|
| ln Vitro |
MC-VC-PABC-DNA31 exhibits potent antitumor activity in vitro through the action of the DNA31 RNA polymerase inhibitor payload. The conjugate demonstrates effective cell killing when incorporated into ADC constructs. The MC-VC-PABC linker allows efficient intracellular release following antibody-mediated internalization and lysosomal processing. The compound shows stability and efficacy in various in vitro assays.
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| ln Vivo |
In vivo, MC-VC-PABC-DNA31 demonstrates potent antitumor activity when used in ADC formats. The conjugate is designed to be stable in systemic circulation while enabling targeted payload delivery to tumors. The MC-VC-PABC linker provides appropriate stability and release kinetics for effective in vivo performance. The DNA31 payload exerts its cytotoxic effects through RNA polymerase inhibition following intracellular release.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for MC-VC-PABC-DNA31 typically involve assessing the linker-payload conjugate's stability and cleavage characteristics. Cathepsin B-mediated release assays are performed by incubating the conjugate with recombinant cathepsin B at pH 5.5, followed by HPLC or LC-MS analysis to quantify DNA31 release kinetics. RNA polymerase inhibition assays may be performed to confirm retained activity of the payload. Plasma stability studies evaluate conjugate integrity.
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| Cell Assay |
In vitro cellular assays for MC-VC-PABC-DNA31 involve testing the conjugate in ADC formats using antigen-positive and antigen-negative cell lines. Cells are treated with varying concentrations (typically 0.001-100 nM range) for 72-120 hours, and cell viability is assessed using MTT, CellTiter-Glo, or similar assays. Internalization studies using labeled constructs confirm antibody-mediated uptake. IC50 values are determined through dose-response curve fitting with appropriate controls.
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| Animal Protocol |
In vivo animal studies for MC-VC-PABC-DNA31 ADC conjugates typically employ xenograft mouse models bearing human tumor cell lines. Tumor-bearing mice are administered the ADC via intravenous injection at doses typically ranging from 1-30 mg/kg on schedules such as single dose or repeat dosing. Tumor growth inhibition is monitored over 2-4 weeks with endpoints including tumor volume measurements, body weight, and survival analysis. Pharmacodynamic biomarkers may be assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MC-VC-PABC-DNA31 conjugates follow typical ADC PK profiles. Following intravenous administration, the conjugate exhibits biphasic elimination with stability in circulation appropriate for antibody-based therapeutics. The MC-VC-PABC linker provides controlled release characteristics. PK parameters including clearance, volume of distribution, and half-life are determined via ELISA and LC-MS/MS methods. Total antibody, conjugate, and free payload concentrations are measured.
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| Toxicity/Toxicokinetics |
Toxicological data for MC-VC-PABC-DNA31 is characteristic of ADC linker-payload constructs. As a research chemical, standard safety precautions should be followed including appropriate PPE and fume hood use. Comprehensive toxicology studies would be required for clinical development. The DNA31 payload is a potent RNA polymerase inhibitor, and handling should follow appropriate safety guidelines for cytotoxic compounds.
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| References | |
| Additional Infomation |
MC-VC-PABC-DNA31 (CAS# 1639352-03-6) is a research-grade drug-linker conjugate for ADC development. It is not approved for clinical use. The compound features the MC-VC-PABC linker, a well-characterized cleavable linker system. DNA31 represents a novel payload class targeting RNA polymerase. This conjugate enables research into RNA polymerase inhibition as a therapeutic strategy for cancer. The compound is typically stored at -20degC under desiccated conditions.
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| Exact Mass |
1496.675
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|---|---|
| CAS # |
1639352-03-6
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| PubChem CID |
136941939
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| Appearance |
Light blue to blue solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
11
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| Hydrogen Bond Acceptor Count |
23
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
108
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| Complexity |
3970
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| Defined Atom Stereocenter Count |
11
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| SMILES |
C[C@H]1/C=C/C=C(\C(=O)NC2=C3C(=C4C(=C(C(=C5C4=C([C@](O5)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)O)C)O)C2=O)N=C6C(=CC(=CC6=O)N7CCC(CC7)NC(=O)OCC8=CC=C(C=C8)NC(=O)[C@H](CCCNC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN9C(=O)C=CC9=O)O3)/C
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| InChi Key |
MJUSLPQDGZEJSC-UFQKGPKISA-N
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| InChi Code |
InChI=1S/C77H96N10O21/c1-38(2)60(83-54(90)20-13-12-14-31-87-55(91)25-26-56(87)92)74(100)82-50(19-16-30-79-75(78)101)73(99)80-47-23-21-46(22-24-47)37-104-76(102)81-48-27-32-86(33-28-48)49-35-51(89)61-53(36-49)107-70-62(84-61)57-58-66(95)44(8)69-59(57)71(97)77(10,108-69)105-34-29-52(103-11)41(5)68(106-45(9)88)43(7)65(94)42(6)64(93)39(3)17-15-18-40(4)72(98)85-63(70)67(58)96/h15,17-18,21-26,29,34-36,38-39,41-43,48,50,52,60,64-65,68,93-95,97H,12-14,16,19-20,27-28,30-33,37H2,1-11H3,(H,80,99)(H,81,102)(H,82,100)(H,83,90)(H,85,98)(H3,78,79,101)/b17-15+,34-29+,40-18-/t39-,41+,42+,43+,50-,52-,60-,64-,65+,68+,77-/m0/s1
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| Chemical Name |
[(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-30-[4-[[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methoxycarbonylamino]piperidin-1-yl]-2,6,15,17-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-23,32,37-trioxo-8,27,38-trioxa-24,34-diazahexacyclo[23.11.1.14,7.05,36.026,35.028,33]octatriaconta-1,3,5,9,19,21,25,28,30,33,35-undecaen-13-yl] acetate
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~33.39 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 3 mg/mL (2.00 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 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: ≥ 3 mg/mL (2.00 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 30.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
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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