General Information of This Peptide-drug Conjugate (PDC)
PDC ID
PDC_00142
PDC Name
Dox-S-S-GFLG-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
Doxorubicin
 Drug Info 
Therapeutic Target
DNA topoisomerase 2-alpha (TOP2A)
 Target Info 
Linker Name
S-S-GFLG-C6
 Linker Info 
Peptide Modified Type
Cyclization modification
Modified Segment
Head-to-tail cyclization
Formula
C99H146N22O32S2
#Ro5 Violations (Lipinski): 5 Molecular Weight 2220.513
Lipid-water partition coefficient (xlogp) -6.84733
Hydrogen Bond Donor Count (hbonddonor) 30
Hydrogen Bond Acceptor Count (hbondacc) 36
Rotatable Bond Count (rotbonds) 47
Full List of Activity Data of This Peptide-drug Conjugate
Revealed Based on the Cell Line Data
Click To Hide/Show 15 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
22%
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).

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP cell CVCL_0395
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
25%
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).

   Click to Show/Hide
In Vitro Model Normal RWPE-1 cell CVCL_3791
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
28%
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).

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cell CVCL_0105
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
38%
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).

   Click to Show/Hide
In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
48%
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.

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 6 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
70%
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.

   Click to Show/Hide
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
74%
Administration Time 2 h
Administration Dosage 100 nM
Description
The conjugate 13, peptide 9, and Dox showed no significant toxicity at or below 10 μM, possibly due to the shorter incubation time of 2 h.
In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 8 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
75%
Administration Time 2 h
Administration Dosage 1 µM
Description
The conjugate 13, peptide 9, and Dox showed no significant toxicity at or below 10 μM, possibly due to the shorter incubation time of 2 h.
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
77%
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.

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 10 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.

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 11 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
98%
Administration Time 2 h
Administration Dosage 100 µM
Description
The conjugate 13, peptide 9, and Dox showed no significant toxicity at or below 10 μM, possibly due to the shorter incubation time of 2 h.
In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 12 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
102%
Administration Time 2 h
Administration Dosage 10 nM
Description
The conjugate 13, peptide 9, and Dox showed no significant toxicity at or below 10 μM, possibly due to the shorter incubation time of 2 h.
In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 13 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
105%
Administration Time 2 h
Administration Dosage 10 µM
Description
The conjugate 13, peptide 9, and Dox showed no significant toxicity at or below 10 μM, possibly due to the shorter incubation time of 2 h.
In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 14 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
108%
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.

   Click to Show/Hide
In Vitro Model Prostate carcinoma LNCaP C4-2 cell CVCL_4782
Experiment 15 Reporting the Activity Data of This PDC [1]
Indication Prostate cancer
Efficacy Data Cell viability
110%
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.

   Click to Show/Hide
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.