Linker Information
General Information of This Linker
| Linker ID |
LIN00076
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| Linker Name |
S-S-GFLG-C6
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| Linker Type |
GSH concentration-sensitive linkers
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| Structure |
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| Formula |
C32H51N7O7S2
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| #Ro5 Violations (Lipinski): 3 | Molecular Weight (mw) | 709.936 | ||||
| Lipid-water partition coefficient (xlogp) | 1.37687 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 8 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 10 | |||||
| Rotatable Bond Count (rotbonds) | 26 | |||||
| Canonical smiles |
CC(C)CC(NC(=O)C(Cc1ccccc1)NC(=O)CNC(=O)C(N)CSSCCCC=N)C(=O)NCC(=O)NCCCCCC(=O)O
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| InChI |
InChI=1S/C32H51N7O7S2/c1-22(2)17-25(31(45)37-19-27(40)35-15-9-4-7-13-29(42)43)39-32(46)26(18-23-11-5-3-6-12-23)38-28(41)20-36-30(44)24(34)21-48-47-16-10-8-14-33/h3,5-6,11-12,14,22,24-26,33H,4,7-10,13,15-21,34H2,1-2H3,(H,35,40)(H,36,44)(H,37,45)(H,38,41)(H,39,46)(H,42,43)/t24-,25-,26-/m0/s1
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| InChIKey |
JSABIZNKUVHFHU-GSDHBNRESA-N
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Each Peptide-drug Conjugate Related to This Linker
Full Information of The Activity Data of The PDC(s) Related to This Linker
Dox-S-S-GFLG-C6-[KTVRTSADE] [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
22%
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| 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 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
25%
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| 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 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
28%
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| 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 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
38%
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| 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 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
48%
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| 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 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
70%
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| 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 7 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
74%
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| 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.
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| 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%
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| 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.
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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 |
77%
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| 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 10 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
78%
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| 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 11 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
98%
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| 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.
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| 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%
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| 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.
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| 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%
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| 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.
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| 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%
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| 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 15 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
110%
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| 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