General Information of This Linker
Linker ID
LIN00062
Linker Name
4-(2-(glycylglycyl)hydrazineylidene)pentanoic acid
Linker Type
Enzyme-sensitive linkers
Structure
Formula
C9H16N4O4
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 244.251
Lipid-water partition coefficient (xlogp) -1.5818
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 5
Rotatable Bond Count (rotbonds) 7
Canonical smiles
CC(CCC(=O)O)=NNC(=O)CNC(=O)CN
InChI
InChI=1S/C9H16N4O4/c1-6(2-3-9(16)17)12-13-8(15)5-11-7(14)4-10/h2-5,10H2,1H3,(H,11,14)(H,13,15)(H,16,17)
InChIKey
NMCVDYCDYFFPHB-UHFFFAOYSA-N
Each Peptide-drug Conjugate Related to This Linker
Full Information of The Activity Data of The PDC(s) Related to This Linker
P-(A5G27scrm)-PTX [Investigative]
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Metastatic Tumor
Efficacy Data Median overall survival (mOS)
40.5 days
Administration Dosage 15 mg/kg PTX equivalent dose
Description
The median survival of mice in the P-(A5G27)-PTX treatment group was longer than in P-(A5G27scrm)-PTX, P-(A5G27), and free PTX-treated groups (48.50 vs 40.5, 43, and 45.5, respectively); however, differences were nonsignificant (Figure 6B).
In Vivo Model 4T1 tumor-bearing mice.
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 Metastatic Tumor
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.221 ± 0.055 µM
Administration Time 72 h
Description
P-(A5G27)-PTX was ˜4-fold more toxic than the nontargeted P-(A5G27scrm)-PTX copolymer, suggesting a faster (receptor-mediated) internalization (Figure 4).
In Vitro Model Mammary carcinoma 4T1 cell CVCL_0125
P-(A5G27)-PTX [Investigative]
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Metastatic Tumor
Efficacy Data Median overall survival (mOS)
48.50 days
Administration Dosage 15 mg/kg PTX equivalent dose
Description
The median survival of mice in the P-(A5G27)-PTX treatment group was longer than in P-(A5G27scrm)-PTX, P-(A5G27), and free PTX-treated groups (48.50 vs 40.5, 43, and 45.5, respectively); however, differences were nonsignificant (Figure 6B).
In Vivo Model 4T1 tumor-bearing mice.
Obtained from the Model Organism Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Metastatic Tumor
Efficacy Data Survival rate
40%
Administration Time 7 days
Administration Dosage 15 mg/kg PTX equivalent dose
Description
P-(A5G27)-PTX prolonged mice survival in 7 and 20% relative to the survival rates of free PTX and nontreated mice, respectively (Figure 5).
In Vivo Model B16-F10 melanoma tumor-bearing mice model.
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 Metastatic Tumor
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.058 ± 0.015 µM
Administration Time 72 h
Description
P-(A5G27)-PTX was ˜4-fold more toxic than the nontargeted P-(A5G27scrm)-PTX copolymer, suggesting a faster (receptor-mediated) internalization (Figure 4).
In Vitro Model Mammary carcinoma 4T1 cell CVCL_0125
References
Ref 1 CD44-Targeted Polymer-Paclitaxel Conjugates to Control the Spread and Growth of Metastatic Tumors. Mol Pharm. 2018 Sep 4;15(9):3690-3699. doi: 10.1021/acs.molpharmaceut.8b00269. Epub 2018 Jun 29.