General Information of This Peptide-drug Conjugate (PDC)
PDC ID
PDC_00132
PDC Name
Doce-βA-thioether-CGFLG-C6-[KTVRTSADE]
PDC Status
Investigative
Indication
In total 1 Indication(s)
Prostate cancer
Structure
Peptide Name
KTVRTSADE
 Peptide Info 
Receptor Name
Fibronectin (FN1)
 Receptor Info 
Drug Name
Docetaxel
 Drug Info 
Therapeutic Target
Microtubule (MT)
 Target Info 
Linker Name
A-thioether-CGFLG-C6
 Linker Info 
Peptide Modified Type
Cyclization modification
Modified Segment
Head-to-tail cyclization
Formula
C126H183N23O39S
#Ro5 Violations (Lipinski): 5 Molecular Weight 2676.039
Lipid-water partition coefficient (xlogp) -4.6345
Hydrogen Bond Donor Count (hbonddonor) 28
Hydrogen Bond Acceptor Count (hbondacc) 41
Rotatable Bond Count (rotbonds) 52
Full List of Activity Data of This Peptide-drug Conjugate
Revealed Based on the Cell Line Data
Click To Hide/Show 10 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
45%
Administration Time 72 h
In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
55%
Administration Time 72 h
Evaluation Method MTS assay
Description
An increase in the cytotoxicity of Dox and Dox/peptide 9 physical mixture as compared to the conjugate 13 over an incubation period of 24 h to 72 h. Conjugates 13 and 14 were found to be less cytotoxic as compared to drug alone in 24-72 h. These cells were not treated with TGF-, so very minimal or no overexpression of EDB-FN. Figure 10b showed the effect of overexpression of EDB-FN in the cell viability. There was no observed effect of TGF- treatment for the cytotoxicity of Dox and physical mixture of Dox/peptide 9 on the cell viability as compared to the TGF- untreated cell lines. However, conjugate 13 showed a decrease in cell viability by 17% after 72 h as compared to untreated cell lines. Similarly, Doce and Doce conjugate 14 showed decrease in cell viability by 16 and 10%, respectively, after 72 h. The physical mixtures of Doce/peptide 9 showed a decrease in cell viability by 16% as compared to untreated cells.

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In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
78%
Administration Time 48 h
Evaluation Method MTS assay
Description
An increase in the cytotoxicity of Dox and Dox/peptide 9 physical mixture as compared to the conjugate 13 over an incubation period of 24 h to 72 h. Conjugates 13 and 14 were found to be less cytotoxic as compared to drug alone in 24-72 h. These cells were not treated with TGF-, so very minimal or no overexpression of EDB-FN. Figure 10b showed the effect of overexpression of EDB-FN in the cell viability. There was no observed effect of TGF- treatment for the cytotoxicity of Dox and physical mixture of Dox/peptide 9 on the cell viability as compared to the TGF- untreated cell lines. However, conjugate 13 showed a decrease in cell viability by 17% after 72 h as compared to untreated cell lines. Similarly, Doce and Doce conjugate 14 showed decrease in cell viability by 16 and 10%, respectively, after 72 h. The physical mixtures of Doce/peptide 9 showed a decrease in cell viability by 16% as compared to untreated cells.

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In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
80%
Administration Time 48 h
Evaluation Method MTS assay
Description
An increase in the cytotoxicity of Dox and Dox/peptide 9 physical mixture as compared to the conjugate 13 over an incubation period of 24 h to 72 h. Conjugates 13 and 14 were found to be less cytotoxic as compared to drug alone in 24-72 h. These cells were not treated with TGF-, so very minimal or no overexpression of EDB-FN. Figure 10b showed the effect of overexpression of EDB-FN in the cell viability. There was no observed effect of TGF- treatment for the cytotoxicity of Dox and physical mixture of Dox/peptide 9 on the cell viability as compared to the TGF- untreated cell lines. However, conjugate 13 showed a decrease in cell viability by 17% after 72 h as compared to untreated cell lines. Similarly, Doce and Doce conjugate 14 showed decrease in cell viability by 16 and 10%, respectively, after 72 h. The physical mixtures of Doce/peptide 9 showed a decrease in cell viability by 16% as compared to untreated cells.

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In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
95%
Administration Time 72 h
Administration Dosage 5 µM
Evaluation Method MTS assay
Description
Dox conjugate 13 was moderately toxic with a reduced cell proliferation to a range of 25-35% as compared to Dox which reduced cell proliferation in the range of 20-34% for all selected four cell lines. However, it was interesting to observe that Doce conjugate 14 was almost nontoxic (cell proliferation within the range of 89-96%) in all the cell lines as compared to Doce alone which reduced the cell proliferation in the range of 54-61% (Figure 9).

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In Vitro Model Normal RWPE-1 cell CVCL_3791
Experiment 6 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
95%
Administration Time 24 h
Evaluation Method MTS assay
Description
An increase in the cytotoxicity of Dox and Dox/peptide 9 physical mixture as compared to the conjugate 13 over an incubation period of 24 h to 72 h. Conjugates 13 and 14 were found to be less cytotoxic as compared to drug alone in 24-72 h. These cells were not treated with TGF-, so very minimal or no overexpression of EDB-FN. Figure 10b showed the effect of overexpression of EDB-FN in the cell viability. There was no observed effect of TGF- treatment for the cytotoxicity of Dox and physical mixture of Dox/peptide 9 on the cell viability as compared to the TGF- untreated cell lines. However, conjugate 13 showed a decrease in cell viability by 17% after 72 h as compared to untreated cell lines. Similarly, Doce and Doce conjugate 14 showed decrease in cell viability by 16 and 10%, respectively, after 72 h. The physical mixtures of Doce/peptide 9 showed a decrease in cell viability by 16% as compared to untreated cells.

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In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 7 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
96%
Administration Time 72 h
Administration Dosage 5 µM
Evaluation Method MTS assay
Description
Dox conjugate 13 was moderately toxic with a reduced cell proliferation to a range of 25-35% as compared to Dox which reduced cell proliferation in the range of 20-34% for all selected four cell lines. However, it was interesting to observe that Doce conjugate 14 was almost nontoxic (cell proliferation within the range of 89-96%) in all the cell lines as compared to Doce alone which reduced the cell proliferation in the range of 54-61% (Figure 9).

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In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 8 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
98%
Administration Time 72 h
Administration Dosage 5 µM
Evaluation Method MTS assay
Description
Dox conjugate 13 was moderately toxic with a reduced cell proliferation to a range of 25-35% as compared to Dox which reduced cell proliferation in the range of 20-34% for all selected four cell lines. However, it was interesting to observe that Doce conjugate 14 was almost nontoxic (cell proliferation within the range of 89-96%) in all the cell lines as compared to Doce alone which reduced the cell proliferation in the range of 54-61% (Figure 9).

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In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 9 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
99%
Administration Time 72 h
Administration Dosage 5 µM
Evaluation Method MTS assay
Description
Dox conjugate 13 was moderately toxic with a reduced cell proliferation to a range of 25-35% as compared to Dox which reduced cell proliferation in the range of 20-34% for all selected four cell lines. However, it was interesting to observe that Doce conjugate 14 was almost nontoxic (cell proliferation within the range of 89-96%) in all the cell lines as compared to Doce alone which reduced the cell proliferation in the range of 54-61% (Figure 9).

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In Vitro Model Prostate carcinoma DU145 cell CVCL_0105
Experiment 10 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
100%
Administration Time 24 h
Evaluation Method MTS assay
Description
An increase in the cytotoxicity of Dox and Dox/peptide 9 physical mixture as compared to the conjugate 13 over an incubation period of 24 h to 72 h. Conjugates 13 and 14 were found to be less cytotoxic as compared to drug alone in 24-72 h. These cells were not treated with TGF-, so very minimal or no overexpression of EDB-FN. Figure 10b showed the effect of overexpression of EDB-FN in the cell viability. There was no observed effect of TGF- treatment for the cytotoxicity of Dox and physical mixture of Dox/peptide 9 on the cell viability as compared to the TGF- untreated cell lines. However, conjugate 13 showed a decrease in cell viability by 17% after 72 h as compared to untreated cell lines. Similarly, Doce and Doce conjugate 14 showed decrease in cell viability by 16 and 10%, respectively, after 72 h. The physical mixtures of Doce/peptide 9 showed a decrease in cell viability by 16% as compared to untreated cells.

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In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
References
Ref 1 EDB-FN Targeted Peptide-Drug Conjugates for Use against Prostate Cancer. Int J Mol Sci. 2019 Jul 4;20(13):3291. doi: 10.3390/ijms20133291.