| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 500mg | |||
| Other Sizes |
| Targets |
Protease Cleavable Linker Cleavable Linker
Mal‑PEG2‑Val‑Cit‑PABA‑PNP has no direct biological target. As an ADC linker, it serves to connect an antibody (via maleimide‑thiol conjugation) and a cytotoxic payload (via PNP carbonate ester). After ADC internalization into target cancer cells, the Val‑Cit peptide sequence is recognized and cleaved by lysosomal cathepsin B, followed by self‑elimination of the PABA spacer to release the active payload. |
|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA‑PNP is a synthetic building block with no direct biological activity. Its function is evaluated as part of a complete ADC in cell‑based assays. Cell viability assays with antigen‑positive cancer cells incubated with ADCs incorporating this linker demonstrate target‑dependent killing, providing indirect evidence of linker functionality. |
| ln Vivo |
A standalone “in vivo activity” for Mal‑PEG2‑Val‑Cit‑PABA‑PNP is not applicable. ADCs constructed with this linker are evaluated in mouse xenograft tumor models, where they show tumor‑specific efficacy (tumor regression) with reduced systemic toxicity compared to non‑cleavable linker ADCs. However, the linker itself is not administered in vivo.
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| Enzyme Assay |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA‑PNP is not used in enzyme/receptor binding assays. However, the Val‑Cit dipeptide sequence can be incorporated into a fluorogenic substrate (e.g., with aminobenzoyl (Abz) and 2,4‑dinitrophenyl (Dnp) groups) to demonstrate cleavage by purified cathepsin B in test tubes, but this is not a standard protocol for this specific linker.
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| Cell Assay |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA‑PNP is not tested directly on cells. Complete ADCs synthesized with this linker are evaluated for target‑dependent cytotoxicity. Antigen‑positive cells are treated with the ADC (0.0001-100 nM) for 72-96 h, and cell viability is measured by CellTiter‑Glo. Cathepsin B dependence is verified by co‑incubation with the cathepsin B inhibitor CA‑074, which should block ADC activity if cleavage is required.
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| Animal Protocol |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA‑PNP alone is not evaluated in animals. ADCs employing this linker are typically administered intravenously (1-10 mg/kg, once weekly for 2-4 weeks) to mice bearing subcutaneous tumor xenografts. Endpoints include tumor volume inhibition, body weight (safety), and determination of released payload in plasma and tumors by LC‑MS/MS to confirm linker cleavage.
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| ADME/Pharmacokinetics |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA‑PNP is a chemical linker not intended for standalone administration. Pharmacokinetic properties (e.g., clearance, half‑life) are determined for the complete ADC. For ADCs, the linker's stability in circulation is critical; Mal‑PEG2‑Val‑Cit‑PABA‑PNP‑based ADCs are designed to be stable in plasma (t½ >7 days) and cleaved efficiently in lysosomes.
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| Toxicity/Toxicokinetics |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA‑PNP is not a drug substance and is not tested in standalone toxicology studies. Toxicity is evaluated for the final ADC. ADCs with Val‑Cit‑PABA cleavable linkers may exhibit off‑target toxicity due to premature payload release in non‑target tissues, but this linker is designed to minimize such effects.
|
| References |
[1]. Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017 May;16(5):315-337.
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| Additional Infomation |
See other relationships...
Mal‑PEG2‑Val‑Cit‑PABA‑PNP is a research‑grade chemical reagent, not a therapeutic agent. It is widely used in ADC research for preclinical development of targeted cancer therapies. The compound has not been approved for human use and is not a clinical trial drug. Its value lies in enabling site‑specific conjugation and controlled intracellular payload release in next‑generation ADCs. |
| Molecular Formula |
C34H41N7O13
|
|---|---|
| Exact Mass |
755.276
|
| CAS # |
1345681-52-8
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| PubChem CID |
142597864
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.6
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
22
|
| Heavy Atom Count |
54
|
| Complexity |
1340
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC(C)[C@@H](C(=O)N[C@@H](CCCNC(=O)N)C(=O)NC1=CC=C(C=C1)COC(=O)OC2=CC=C(C=C2)[N+](=O)[O-])NC(=O)OCCOCCN3C(=O)C=CC3=O
|
| InChi Key |
VZRMIJHOKYFMIG-WNJJXGMVSA-N
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| InChi Code |
InChI=1S/C34H41N7O13/c1-21(2)29(39-33(47)52-19-18-51-17-16-40-27(42)13-14-28(40)43)31(45)38-26(4-3-15-36-32(35)46)30(44)37-23-7-5-22(6-8-23)20-53-34(48)54-25-11-9-24(10-12-25)41(49)50/h5-14,21,26,29H,3-4,15-20H2,1-2H3,(H,37,44)(H,38,45)(H,39,47)(H3,35,36,46)/t26-,29-/m0/s1
|
| Chemical Name |
[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethoxycarbonylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate
|
| 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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
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