Linker Information

General Information of This Linker
Linker ID
LIN00048
Linker Name
Ahx-Val
Linker Type
Enzyme-sensitive linkers
Structure
Formula
C8H16N2O2
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 172.228
Lipid-water partition coefficient (xlogp) 0.529
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 2
Rotatable Bond Count (rotbonds) 4
Canonical smiles
CC(C)CNC(=O)NC(C)C=O
InChI
InChI=1S/C8H16N2O2/c1-6(2)4-9-8(12)10-7(3)5-11/h5-7H,4H2,1-3H3,(H2,9,10,12)/t7-/m1/s1
InChIKey
FUXAVZHTOUQWKK-SSDOTTSWSA-N
Each Peptide-drug Conjugate Related to This Linker
Full Information of The Activity Data of The PDC(s) Related to This Linker
T7-SN-38 [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Glioblastoma
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
70.07nM
Administration Time 72 h
Evaluation Method XTT assay
MOA of PDC
In the present work, the cytotoxic drug SN-38 is coupled to the tumor-targeting T7 peptide via a cathepsin B cleavable VA peptide linker. This ensures that the drug remains covalently bound until it reaches the intended site of action, where Cat B is overexpressed to release the drug. Within this framework, our research pursuits entail the synthesis and characterization of a T7-SN-38-targeted drug conjugate using strain-promoted azide-alkyne cycloaddition (SPAAC). Our investigation extended to evaluating the cellular uptake and assessing the cytotoxicity of the drug conjugate in U87MG glioblastoma cells.

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Description
Further, IC50values of SN-38 and T7-SN-38 on U87MG cells at 72 h were determined. An estimated IC50value of 26.41nM was obtained for SN-38, which was considerably lower than an IC50value of 70.07nM obtained for the T7-SN-38 conjugate. These IC50data confirm the greater cytotoxicity of the pure drug compared to the conjugate at 72 h (p< 0.05).
In Vitro Model Glioblastoma U-87MG cell CVCL_0022
References
Ref 1 Development of a Targeted SN-38-Conjugate for the Treatment of Glioblastoma. ACS Omega. 2024 Jan 4;9(2):2615-2628. doi: 10.1021/acsomega.3c07486. eCollection 2024 Jan 16.