| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Protease Cleavable Linker Cleavable Linker
Mal‑PEG2‑Val‑Cit‑PABA has no biological target of its own. It serves as a structural linker in ADCs, enabling stable antibody‑payload conjugation and controlled intracellular release of the cytotoxin. The maleimide group reacts with thiols on antibodies, while the Val‑Cit peptide is specifically cleaved by cathepsin B inside lysosomes after ADC internalization into target cells. |
|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA is a synthetic building block for ADC construction and has no direct biological activity. Its utility is indirectly assessed through the in vitro potency of the resulting complete ADC. ADCs incorporating this linker typically exhibit potent and selective killing of antigen‑positive cancer cells while sparing antigen‑negative cells. |
| ln Vivo |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA is not administered in vivo as a standalone compound. ADCs constructed with this linker are evaluated in mouse xenograft tumor models to demonstrate target‑specific efficacy. These ADCs typically show significant tumor growth inhibition (TGI ≥80%) with a favorable safety profile (minimal body weight loss).
|
| Enzyme Assay |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA is not used in direct enzyme/receptor binding assays. However, to confirm that the Val‑Cit sequence is cleavable, a model peptide containing this sequence and a fluorophore can be synthesized; upon incubation with purified cathepsin B (10-100 nM), fluorescence increases due to cleavage, but this is not a standard protocol for the linker itself.
|
| Cell Assay |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA is not tested directly on cells. The functional assay involves treating antigen‑positive cancer cells (e.g., HER2‑positive SK‑BR‑3 cells) with the complete ADC (0.0001-100 nM) for 72-96 h. Cell viability is measured by CellTiter‑Glo. Co‑incubation with cathepsin B inhibitors (e.g., CA‑074) should block ADC activity, confirming that Val‑Cit cleavage is required for efficacy.
|
| Animal Protocol |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA alone is not evaluated in animals. An ADC incorporating this linker is typically administered intravenously at 1-10 mg/kg once weekly for 2-4 weeks in mouse xenograft models. Tumor volume is measured twice weekly. After the final dose, plasma and tumor tissues are analyzed by LC‑MS/MS to quantify released payload, providing evidence of linker cleavage in vivo.
|
| ADME/Pharmacokinetics |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA is a chemical linker not intended for standalone administration. For ADCs built with this linker, the linker contributes to favorable pharmacokinetics, including low plasma clearance, extended ADC half‑life (several days), and minimal release of free payload into circulation, thereby maintaining a high therapeutic index.
|
| Toxicity/Toxicokinetics |
Not applicable; Mal‑PEG2‑Val‑Cit‑PABA is not a drug substance and is not tested in standalone toxicology studies. For ADCs incorporating this linker, toxicity is evaluated and may include payload‑related off‑target effects (e.g., neutropenia, hepatotoxicity). The Val‑Cit‑PABA cleavable linker is generally associated with a wider therapeutic window compared to non‑cleavable linkers.
|
| References |
[1]. Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315-337.
|
| Additional Infomation |
Mal‑PEG2‑Val‑Cit‑PABA is a research‑grade chemical reagent widely used in ADC development. It is not a therapeutic agent and has not been approved for human use. The compound is particularly valuable for designing ADCs that require controlled intracellular payload release, as the Val‑Cit dipeptide is efficiently cleaved by cathepsin B in lysosomes, while remaining stable in circulation. No clinical trials are registered for this specific linker.
|
| Molecular Formula |
C27H38N6O9
|
|---|---|
| Exact Mass |
590.27
|
| CAS # |
1662687-83-3
|
| PubChem CID |
156306412
|
| Appearance |
White to off-white solid powder
|
| LogP |
-0.7
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
42
|
| Complexity |
963
|
| 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)CO)NC(=O)OCCOCCN2C(=O)C=CC2=O
|
| InChi Key |
HTNGHIKQRXTBSP-REWPJTCUSA-N
|
| InChi Code |
InChI=1S/C27H38N6O9/c1-17(2)23(32-27(40)42-15-14-41-13-12-33-21(35)9-10-22(33)36)25(38)31-20(4-3-11-29-26(28)39)24(37)30-19-7-5-18(16-34)6-8-19/h5-10,17,20,23,34H,3-4,11-16H2,1-2H3,(H,30,37)(H,31,38)(H,32,40)(H3,28,29,39)/t20-,23-/m0/s1
|
| Chemical Name |
2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethyl N-[(2S)-1-[[(2S)-5-(carbamoylamino)-1-[4-(hydroxymethyl)anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
|
| 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 |
| 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
|
|---|---|
| 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
