| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
The primary molecular target is the microtubule protein tubulin. The MMAE payload is a potent inhibitor of tubulin polymerization. Upon internalization of the ADC into target cells (e.g., cancer cells) and subsequent lysosomal degradation, the Val-Cit linker is cleaved by cathepsin B. This triggers the PAB spacer to release the active MMAE, which then binds to tubulin, disrupting the microtubule network and leading to cell cycle arrest in the G2/M phase, followed by apoptosis.
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| ln Vitro |
As a linker-payload construct, its activity is measured through the efficacy of the ADC produced. The released MMAE is highly potent, with IC₅0 values in the low nanomolar to picomolar range against various cancer cell lines. The Val-Cit-PAB linker is stable in systemic circulation but is efficiently cleaved by lysosomal proteases (specifically cathepsin B) inside target cells, ensuring that the cytotoxic payload is only released intracellularly, minimizing systemic toxicity.
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| ln Vivo |
No direct in vivo activity data is available for the unconjugated linker. The therapeutic activity is derived from the ADC constructed using this molecule. In animal models (xenografts), ADCs constructed with cleavable linkers like Val-Cit-PAB and MMAE payloads generally demonstrate significant antitumor efficacy at well-tolerated doses, often inducing complete tumor regression. The ADC specifically delivers MMAE to antigen-expressing tumor cells, leading to tumor growth inhibition and improved survival.
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| Enzyme Assay |
A non-cell-based assay verifies the linker‘s stability. The linker is incubated in human plasma at 37degC for 24-72 hours. Samples are analyzed by LC-MS/MS to detect the presence of the intact linker and any released MMAE. The Val-Cit-PAB linker should show minimal cleavage (<5%) in plasma, confirming its stability. Separately, a cathepsin B cleavage assay is performed by incubating the linker with the purified enzyme in an acetate buffer (pH 5.5). Cleavage is quantified by LC-MS/MS to measure the release of MMAE.
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| Cell Assay |
The conjugated activity is tested using a cell viability assay. Target antigen-positive and antigen-negative cells are seeded in 96-well plates. The ADC constructed using DBCO-(PEG2-VC-PAB-MMAE)2 is added at serial dilutions and incubated for 72-96 hours. Cell viability is assessed using CellTiter-Glo (ATP quantification) or MTT assay. The DC₅0 (antibody concentration required to kill 50% of cells) is calculated. Antigen-negative cells should show no cytotoxicity, demonstrating target specificity.
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| Animal Protocol |
In vivo protocols involve constructing a specific ADC. For efficacy studies, mice bearing xenograft tumors (size ~150 mm3) are randomized into treatment groups (n=5-10). The ADC is administered intravenously (e.g., 1, 3, 10 mg/kg) once weekly for three weeks. Tumor volumes are measured bi-weekly with calipers. At the endpoint, tumors and major organs are harvested for histology and TUNEL staining to evaluate apoptosis and off-target toxicity.
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| ADME/Pharmacokinetics |
PK properties are determined for the ADC. The linker‘s unique function is to remain stable in the bloodstream (t1/2 of conjugate may be ~5-7 days) but release MMAE efficiently in the tumor. For the ADC conjugate, the clearance is typically biphasic. The peak concentration (Cmax) and area under the curve (AUC) for the intact ADC are dose-dependent. The linker itself is metabolized by proteases, and the released MMAE is primarily metabolized by CYP3A4 in the liver. As a research chemical, the linker's molecular weight is 2835.50 g/mol and it is soluble in DMSO (100 mg/mL).
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| Toxicity/Toxicokinetics |
The toxicity data for this compound is derived from the MMAE payload, which causes systemic toxicity if released prematurely. In animal models, the main dose-limiting toxicities of MMAE-based ADCs are neutropenia, peripheral neuropathy, and gastrointestinal effects. However, the Val-Cit-PAB linker is designed to be stable in circulation (half-life ~2 days in plasma), which significantly reduces these off-target effects. Acute toxicity studies of the linker-payload itself are not standard, as it is not administered unconjugated in vivo.
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| References | |
| Additional Infomation |
DBCO-(PEG2-VC-PAB-MMAE)2 is a sophisticated third-generation linker-payload platform. It is not a drug itself but a critical component for ADC development. It utilizes copper-free click chemistry (SPAAC) for efficient conjugation. The “2” in the name indicates a dual-payload design (dimer). It is currently used in preclinical research and development to produce novel ADCs for cancer therapy. No ADC containing this specific linker has yet received full FDA or EMA approval for clinical use, as it represents an advanced modular platform for next-generation drug conjugation.
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| Molecular Formula |
C149H224N22O32
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|---|---|
| Molecular Weight |
2835.50
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| Exact Mass |
2834.661
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| CAS # |
2259318-55-1
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| PubChem CID |
145712369
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| Appearance |
White to light yellow solid powder
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| LogP |
10.3
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| Hydrogen Bond Donor Count |
16
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| Hydrogen Bond Acceptor Count |
32
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| Rotatable Bond Count |
87
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| Heavy Atom Count |
203
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| Complexity |
5790
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| Defined Atom Stereocenter Count |
24
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| SMILES |
C(N1CC2=CC=CC=C2C#CC2=CC=CC=C12)(=O)CCC(=O)N(CCOCCOCCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=O)N)C(=O)NC1C=CC(COC(=O)N(C)[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@]([H])([C@@H](C)CC)[C@H](OC)CC(N2CCC[C@@]2([H])[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@H](C2C=CC=CC=2)O)=O)=CC=1)CCOCCOCCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=O)N)C(=O)NC1C=CC(COC(=O)N(C)[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@]([H])([C@@H](C)CC)[C@H](OC)CC(N2CCC[C@@]2([H])[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@H](C2C=CC=CC=2)O)=O)=CC=1
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| InChi Key |
VVUBUMFIIJDYES-VRRJACBRSA-N
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| InChi Code |
InChI=1S/C149H224N22O32/c1-29-96(15)130(116(194-25)85-122(176)169-73-43-55-114(169)134(196-27)98(17)136(180)154-100(19)132(178)106-47-33-31-34-48-106)164(21)144(188)126(92(7)8)162-142(186)128(94(11)12)166(23)148(192)202-88-102-57-63-109(64-58-102)156-138(182)111(52-41-71-152-146(150)190)158-140(184)124(90(3)4)160-118(172)69-77-198-81-83-200-79-75-168(120(174)67-68-121(175)171-87-108-51-38-37-45-104(108)61-62-105-46-39-40-54-113(105)171)76-80-201-84-82-199-78-70-119(173)161-125(91(5)6)141(185)159-112(53-42-72-153-147(151)191)139(183)157-110-65-59-103(60-66-110)89-203-149(193)167(24)129(95(13)14)143(187)163-127(93(9)10)145(189)165(22)131(97(16)30-2)117(195-26)86-123(177)170-74-44-56-115(170)135(197-28)99(18)137(181)155-101(20)133(179)107-49-35-32-36-50-107/h31-40,45-51,54,57-60,63-66,90-101,111-112,114-117,124-135,178-179H,29-30,41-44,52-53,55-56,67-89H2,1-28H3,(H,154,180)(H,155,181)(H,156,182)(H,157,183)(H,158,184)(H,159,185)(H,160,172)(H,161,173)(H,162,186)(H,163,187)(H3,150,152,190)(H3,151,153,191)/t96-,97-,98+,99+,100+,101+,111-,112-,114-,115-,116+,117+,124-,125-,126-,127-,128-,129-,130-,131-,132+,133+,134+,135+/m0/s1
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| Chemical Name |
[4-[[(2S)-2-[[(2S)-2-[3-[2-[2-[[4-(2-azatricyclo[10.4.0.04,9]hexadeca-1(16),4,6,8,12,14-hexaen-10-yn-2-yl)-4-oxobutanoyl]-[2-[2-[3-[[(2S)-1-[[(2S)-5-(carbamoylamino)-1-[4-[[[(2S)-1-[[(2S)-1-[[(3R,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]-methylcarbamoyl]oxymethyl]anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropoxy]ethoxy]ethyl]amino]ethoxy]ethoxy]propanoylamino]-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,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: 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 : ~50 mg/mL (~17.63 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 | 0.3527 mL | 1.7634 mL | 3.5267 mL | |
| 5 mM | 0.0705 mL | 0.3527 mL | 0.7053 mL | |
| 10 mM | 0.0353 mL | 0.1763 mL | 0.3527 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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