Linker Information
General Information of This Linker
| Linker ID |
LIN00082
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| Linker Name |
A-thioether-CGFLG-C6
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| Linker Type |
Enzyme-sensitive linkers
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| Structure |
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| Formula |
C43H64N8O12S
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| #Ro5 Violations (Lipinski): 4 | Molecular Weight (mw) | 917.096 | ||||
| Lipid-water partition coefficient (xlogp) | -0.1763 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 9 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 12 | |||||
| Rotatable Bond Count (rotbonds) | 28 | |||||
| Canonical smiles |
CC(C)CC(NC(=O)C(Cc1ccccc1)NC(=O)CNC(=O)C(N)CSC1CC(=O)N(CC2CCC(C(=O)NCCC(=O)O)CC2)C1=O)C(=O)NCC(=O)NCCCCCC(=O)O
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| InChI |
InChI=1S/C43H64N8O12S/c1-26(2)19-31(41(61)48-22-34(52)45-17-8-4-7-11-37(55)56)50-42(62)32(20-27-9-5-3-6-10-27)49-35(53)23-47-40(60)30(44)25-64-33-21-36(54)51(43(33)63)24-28-12-14-29(15-13-28)39(59)46-18-16-38(57)58/h3,5-6,9-10,26,28-33H,4,7-8,11-25,44H2,1-2H3,(H,45,52)(H,46,59)(H,47,60)(H,48,61)(H,49,53)(H,50,62)(H,55,56)(H,57,58)/t28?,29?,30-,31-,32-,33?/m0/s1
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| InChIKey |
AWKMDRJXVQXNOE-SPHWINDJSA-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
Doce-βA-thioether-CGFLG-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 |
45%
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| 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%
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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 3 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 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
80%
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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 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
95%
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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 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
95%
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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 7 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
96%
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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 8 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
98%
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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 9 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
99%
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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 10 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Cell viability |
100%
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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