| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Cleavable Linker
No direct pharmacological target; serves as a drug-linker conjugate for ADCs and targeted protein degradation. The endo-BCN group reacts with azide-tagged antibodies via strain-promoted alkyne-azide cycloaddition (SPAAC) click chemistry. The Val-Cit-PAB linker is cleavable by cathepsin B in lysosomes. |
|---|---|
| ln Vitro |
An ADC linker attaches the ADC cytotoxin to an antibody, which makes up ADC [1].
As an ADC linker-drug conjugate, endo-BCN-PEG4-Val-Cit-PAB-MMAE itself is the payload portion of an ADC. When conjugated to a tumor-targeting antibody, the ADC binds to cancer cell surface antigens, undergoes receptor-mediated endocytosis, and enters lysosomes where cathepsin B cleaves the Val-Cit-PAB linker, releasing free MMAE which inhibits tubulin polymerization (IC50 ~ 1-5 nM for tubulin polymerization, induces G2/M arrest and apoptosis). |
| ln Vivo |
In vivo, MMAE-based ADCs generally exhibit potent anti-tumor activity in xenograft models. Tumor-targeting antibodies conjugated via the endo-BCN-PEG4-Val-Cit-PAB-MMAE construct typically produce dose-dependent tumor regression in murine xenografts at 1-10 mg/kg, administered IV once weekly for 2-3 cycles. The cleavable linker ensures intracellular drug release and bystander killing effects on neighboring antigen-negative tumor cells.
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| Enzyme Assay |
Not applicable as the compound does not directly bind to a soluble enzyme/receptor; instead, it relies on ADC conjugation. However, cathepsin B-mediated linker cleavage can be studied by incubating the linker-drug conjugate with recombinant human cathepsin B (50 nM, pH 5.5, 37degC, 2 h), then analyzing released MMAE by LC-MS/MS.
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| Cell Assay |
(1) Plate antigen-positive cancer cells in 96-well plates overnight. (2) Treat with MMAE alone (0.01-100 nM, 72 h) or with the fully conjugated ADC. (3) Add CellTiter-Glo reagent (incubate 10 min) and measure luminescence for viability. (4) Alternatively, for apoptosis: stain with Annexin V-FITC/PI after 48 h treatment, analyze by flow cytometry for G2/M arrest. (5) For tubulin polymerization: use the Tubulin Polymerization Assay Kit (fluorescence-based).
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| Animal Protocol |
(1) Use 6-8 week old female BALB/c nude mice bearing tumor xenografts (200-300 mm3). (2) Administer ADC or vehicle control via tail vein IV injection (1-10 mg/kg, q7d × 2-3 cycles). (3) Formulation: for ADC conjugates, use PBS; for the linker-drug itself, dissolve in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. (4) Monitor tumor volume and body weight twice weekly. (5) Collect plasma for PK analysis and tumors for IHC (cleaved caspase-3, Ki-67) and TUNEL assays.
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| ADME/Pharmacokinetics |
As a highly hydrophobic ADC payload, MMAE requires conjugation to antibodies for in vivo use. Unconjugated linker-drug has rapid clearance (t1/2 ~ 0.5-2 h) and poor PK. When conjugated to antibody, the ADC exhibits long circulation half-life (t1/2 ~ 2-7 days, species-dependent), low Cmax (due to slow release), and minimal non-specific accumulation. The PEG4 spacer improves water solubility of the conjugate.
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| Toxicity/Toxicokinetics |
Off-target toxicity: Free MMAE from premature linker cleavage (IC50 ~ 1-5 nM on dividing cells) causes neutropenia, peripheral neuropathy (due to tubulin inhibition in neurons), and thrombocytopenia in vivo. For ADC conjugates, MTD is typically 5-15 mg/kg in mice (IV, q7d × 3). Histopathology: observe bone marrow hypocellularity, gastrointestinal epithelial apoptosis, and peripheral nerve degeneration.
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| References | |
| Additional Infomation |
endo-BCN-PEG4-Val-Cit-PAB-MMAE is both an ADC linker-drug conjugate and a click chemistry reagent. The endo-BCN group enables strain-promoted alkyne-azide cycloaddition (SPAAC) with azide-tagged antibodies without copper catalysts, making it suitable for in vivo conjugation applications. The Val-Cit-PAB linker is specifically cleaved by cathepsin B, an enzyme overexpressed in many cancer types, ensuring tumor-selective MMAE release. This compound is used in the synthesis of site-specific ADCs and has been studied in various cancer models, but it is not FDA-approved. It is strictly for research use only.
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| Molecular Formula |
C80H127N11O19
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|---|---|
| Molecular Weight |
1546.92670273781
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| Exact Mass |
1545.93
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| CAS # |
2762519-08-2
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| PubChem CID |
139593571
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| Appearance |
White to off-white solid powder
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| LogP |
6.1
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
51
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| Heavy Atom Count |
110
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| Complexity |
2900
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| Defined Atom Stereocenter Count |
11
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| SMILES |
CC[C@H](C)[C@@H](C(CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)OCC3=CC=C(C=C3)NC(=O)[C@H](CCCNC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)CCOCCOCCOCCOCCNC(=O)OCC4C5C4CCC#CCC5
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| InChi Key |
SQKNRIOHJGDSGO-ZTFVZQKWSA-N
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| InChi Code |
InChI=1S/C80H127N11O19/c1-15-53(8)70(64(103-13)47-66(93)91-38-24-30-63(91)72(104-14)54(9)73(95)84-55(10)71(94)57-25-19-18-20-26-57)89(11)77(99)68(51(4)5)88-76(98)69(52(6)7)90(12)80(102)110-48-56-31-33-58(34-32-56)85-74(96)62(29-23-36-82-78(81)100)86-75(97)67(50(2)3)87-65(92)35-39-105-41-43-107-45-46-108-44-42-106-40-37-83-79(101)109-49-61-59-27-21-16-17-22-28-60(59)61/h18-20,25-26,31-34,50-55,59-64,67-72,94H,15,21-24,27-30,35-49H2,1-14H3,(H,83,101)(H,84,95)(H,85,96)(H,86,97)(H,87,92)(H,88,98)(H3,81,82,100)/t53-,54+,55+,59?,60?,61?,62-,63-,64?,67-,68-,69-,70-,71+,72+/m0/s1
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| Chemical Name |
[4-[[(2S)-2-[[(2S)-2-[3-[2-[2-[2-[2-(9-bicyclo[6.1.0]non-4-ynylmethoxycarbonylamino)ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate
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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). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 :~200 mg/mL (~129.29 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (3.23 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 50.0 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: 5 mg/mL (3.23 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: 5 mg/mL (3.23 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6464 mL | 3.2322 mL | 6.4644 mL | |
| 5 mM | 0.1293 mL | 0.6464 mL | 1.2929 mL | |
| 10 mM | 0.0646 mL | 0.3232 mL | 0.6464 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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