Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00071
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| PDC Name |
c[DKP-RGD]-PEG4-sC18(dau=Aoa-GFLG-Lys8)
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| PDC Status |
Investigative
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| Indication |
In total 1 Indication(s)
Tumor
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| Structure |
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| Peptide Name |
c[DKP-RGD]-PEG4-sC18
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Peptide Info | ||||
| Drug Name |
Daunorubicin
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Drug Info | ||||
| Therapeutic Target |
DNA topoisomerase 2-alpha (TOP2A)
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Target Info | ||||
| Linker Name |
GFLG
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Linker Info | ||||
| Peptide Modified Type |
The modification of binding with chemical macromolecules
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| Modified Segment |
c[DKP-RGD]
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| Ternimal Modification |
N-terminal modification
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| Formula |
C181H284N54O47
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| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 3968.594 | ||||
| Lipid-water partition coefficient (xlogp) | -13.30773 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 51 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 60 | |||||
| Rotatable Bond Count (rotbonds) | 131 | |||||
Full List of Activity Data of This Peptide-drug Conjugate
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
2.7 μM
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| Administration Time | 72 h | ||||
| Description |
All dau-loaded conjugates showed high toxicity in all cell lines tested with EC50 values in the lower micromolar range.
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| In Vitro Model | Invasive breast carcinoma | MCF-7 cell | CVCL_0031 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
3.9 μM
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| Administration Time | 72 h | ||||
| Description |
All dau-loaded conjugates showed high toxicity in all cell lines tested with EC50 values in the lower micromolar range.
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| In Vitro Model | Glioblastoma | U87 cell | CVCL_3429 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
7.8 μM
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| Administration Time | 15 min | ||||
| Description |
More specifically, compounds1band3bdemonstrated significantly higher activity against U87 cells compared to MCF-7 and HT-29 cells (Figure6). Importantly,1bwas more active than3bdemonstrating that the attached CPP is indeed necessary to increase the overall cellular uptake and thus cytotoxic activity of the conjugates. Of note is also that2bwas less efficient than1bbut marginally more active than3b, although with no selectivity. For the two conjugates bearing the GFLG motif, it was seen that3cis still significantly more active in U87 cells expressing integrin receptors. By contrast,1ckept its selectivity against HT-29 cells, but was pronouncedly more active in MCF-7 cells compared to1b.
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| In Vitro Model | Invasive breast carcinoma | MCF-7 cell | CVCL_0031 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
11 μM
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| Administration Time | 72 h | ||||
| Description |
All dau-loaded conjugates showed high toxicity in all cell lines tested with EC50 values in the lower micromolar range.
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| In Vitro Model | Colon cancer | HT29 cell | CVCL_A8EZ | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
23.8 μM
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| Administration Time | 15 min | ||||
| Description |
More specifically, compounds1band3bdemonstrated significantly higher activity against U87 cells compared to MCF-7 and HT-29 cells (Figure6). Importantly,1bwas more active than3bdemonstrating that the attached CPP is indeed necessary to increase the overall cellular uptake and thus cytotoxic activity of the conjugates. Of note is also that2bwas less efficient than1bbut marginally more active than3b, although with no selectivity. For the two conjugates bearing the GFLG motif, it was seen that3cis still significantly more active in U87 cells expressing integrin receptors. By contrast,1ckept its selectivity against HT-29 cells, but was pronouncedly more active in MCF-7 cells compared to1b.
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| In Vitro Model | Glioblastoma | U87 cell | CVCL_3429 | ||
| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
89.1 μM
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| Administration Time | 15 min | ||||
| Description |
More specifically, compounds1band3bdemonstrated significantly higher activity against U87 cells compared to MCF-7 and HT-29 cells (Figure6). Importantly,1bwas more active than3bdemonstrating that the attached CPP is indeed necessary to increase the overall cellular uptake and thus cytotoxic activity of the conjugates. Of note is also that2bwas less efficient than1bbut marginally more active than3b, although with no selectivity. For the two conjugates bearing the GFLG motif, it was seen that3cis still significantly more active in U87 cells expressing integrin receptors. By contrast,1ckept its selectivity against HT-29 cells, but was pronouncedly more active in MCF-7 cells compared to1b.
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| In Vitro Model | Colon cancer | HT29 cell | CVCL_A8EZ | ||
References