Fmoc-Val-Cit-PAB-PNP

Name: Fmoc-Val-Cit-PAB-PNP
Brand: MedChemExpress
SKU: HY-41189
Rating: 4.5 (1 reviews)

Cat. No.: HY-41189 Purity: 98.99%: Data Sheet
SDS

COA
Handling Instructions
FAQs
Technical Support

Fmoc-Val-Cit-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-Val-Cit-PAB-PNP has superior plasma stability comparable to that of non-cleavable linkers.

For research use only. We do not sell to patients.

Fmoc-Val-Cit-PAB-PNP Chemical Structure

CAS No. : 863971-53-3

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Customer Review

Based on 1 publication(s) in Google Scholar

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Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

Protease Cleavable Linker

Cleavable Linker

In Vitro

Fmoc-Val-Cit-PAB-PNP contains peptide sequence degradable by a lysosome enzyme^[1].
Cathepsin B in the lysosome cleaves the peptide bond between Cit-PAB of dipeptide linkers containing Valine (Val)-citrulline (Cit) and p-aminobenzylalcohol (PAB). When PAB and a drug are binded covalently with carbamate bonds, the drug can be released by hydrolysis after cleavage of the peptide bond between Cit-PAB. Antibody-drug conjugates (ADCs) has been developed using this mechanism^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Fmoc-Val-Cit-PAB-PNP linker stabilization in the mouse is an essential prerequisite for designing successful efficacy and safety studies in rodents during preclinical stages of ADC programs^[3].
Conjugation site plays an important role in determining VC-PABC linker stability in mouse plasma, and that the stability of the linker positively correlates with ADC cytotoxic potency both in vitro and in vivo^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

766.80

Formula

C₄₀H₄₂N₆O₁₀

CAS No.

863971-53-3

Appearance

Solid

Color

White to yellow

Sequence Shortening

Fmoc-V-Cit-PAB-PNP

SMILES

CC(C)[C@@H](C(N[C@@H](CCCNC(N)=O)C(NC1=CC=C(COC(OC2=CC=C([N+]([O-])=O)C=C2)=O)C=C1)=O)=O)NC(OCC3C4=C(C5=C3C=CC=C5)C=CC=C4)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility

In Vitro:

DMSO : ≥ 40 mg/mL (52.16 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.3041 mL	6.5206 mL	13.0412 mL
5 mM	0.2608 mL	1.3041 mL	2.6082 mL
10 mM	0.1304 mL	0.6521 mL	1.3041 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 5.25 mg/mL (6.85 mM); Clear solution

This protocol yields a clear solution of ≥ 5.25 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (52.5 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.99%

Select Batch:

Data Sheet (278 KB) SDS (393 KB)

COA (255 KB) HNMR (144 KB) LCMS (106 KB)

Handling Instructions (2659 KB)

References

[1]. Dubowchik GM, et al. Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: model studies of enzymatic drug release and antigen-specific in vitro anticancer activity. Bioconjug Chem. 2002 Jul-Aug;13(4):855-69. [Content Brief]

[2]. Yoneda Y, et al. A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy. Bioorg Med Chem Lett. 2008 Mar 1;18(5):1632-6. [Content Brief]

[3]. Dorywalska M, et al. Effect of attachment site on stability of cleavable antibody drug conjugates. Bioconjug Chem. 2015 Apr 15;26(4):650-9. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.3041 mL	6.5206 mL	13.0412 mL	32.6030 mL
	5 mM	0.2608 mL	1.3041 mL	2.6082 mL	6.5206 mL
	10 mM	0.1304 mL	0.6521 mL	1.3041 mL	3.2603 mL
	15 mM	0.0869 mL	0.4347 mL	0.8694 mL	2.1735 mL
	20 mM	0.0652 mL	0.3260 mL	0.6521 mL	1.6302 mL
	25 mM	0.0522 mL	0.2608 mL	0.5216 mL	1.3041 mL
	30 mM	0.0435 mL	0.2174 mL	0.4347 mL	1.0868 mL
	40 mM	0.0326 mL	0.1630 mL	0.3260 mL	0.8151 mL
	50 mM	0.0261 mL	0.1304 mL	0.2608 mL	0.6521 mL