Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00072
|
|||||
|---|---|---|---|---|---|---|
| PDC Name |
c[DKP-RGD]-PEG4-sC18(dau=Aoa-Lys8)
|
|||||
| PDC Status |
Investigative
|
|||||
| Indication |
In total 1 Indication(s)
Tumor
|
|||||
| Structure |
|
|||||
| Peptide Name |
c[DKP-RGD]-PEG4-sC18
|
Peptide Info | ||||
| Drug Name |
Daunorubicin
|
Drug Info | ||||
| Therapeutic Target |
DNA topoisomerase 2-alpha (TOP2A)
|
Target Info | ||||
| Linker Name |
Aminooxyacetic acid
|
Linker Info | ||||
| Peptide Modified Type |
The modification of binding with chemical macromolecules
|
|||||
| Modified Segment |
c[DKP-RGD]
|
|||||
| Ternimal Modification |
N-terminal modification
|
|||||
| Formula |
C162H258N50O43
|
|||||
| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 3594.153 | ||||
| Lipid-water partition coefficient (xlogp) | -12.79853 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 47 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 56 | |||||
| Rotatable Bond Count (rotbonds) | 119 | |||||
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) |
3 μM
|
|||
| 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.
|
||||
| In Vitro Model | Colon cancer | HT29 cell | CVCL_A8EZ | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
5.6 μM
|
|||
| 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.
|
||||
| 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) |
9.1 μM
|
|||
| 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.
|
||||
| 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) |
12.5 μM
|
|||
| Administration Time | 15 min | ||||
| Description |
More specifically, compounds 1b and 3b demonstrated significantly higher activity against U87 cells compared to MCF-7 and HT-29 cells (Figure 6). Importantly, 1b was more active than 3b demonstrating that the attached CPP is indeed necessary to increase the overall cellular uptake and thus cytotoxic activity of the conjugates. Of note is also that 2b was less efficient than 1b but marginally more active than 3b, although with no selectivity. For the two conjugates bearing the GFLG motif, it was seen that 3c is still significantly more active in U87 cells expressing integrin receptors. By contrast, 1c kept its selectivity against HT-29 cells, but was pronouncedly more active in MCF-7 cells compared to 1b.
Click to Show/Hide
|
||||
| In Vitro Model | Glioblastoma | U87 cell | CVCL_3429 | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
50.5 μM
|
|||
| Administration Time | 15 min | ||||
| Description |
More specifically, compounds 1b and 3b demonstrated significantly higher activity against U87 cells compared to MCF-7 and HT-29 cells (Figure 6). Importantly, 1b was more active than 3b demonstrating that the attached CPP is indeed necessary to increase the overall cellular uptake and thus cytotoxic activity of the conjugates. Of note is also that 2b was less efficient than 1b but marginally more active than 3b, although with no selectivity. For the two conjugates bearing the GFLG motif, it was seen that 3c is still significantly more active in U87 cells expressing integrin receptors. By contrast, 1c kept its selectivity against HT-29 cells, but was pronouncedly more active in MCF-7 cells compared to 1b.
Click to Show/Hide
|
||||
| In Vitro Model | Colon cancer | HT29 cell | CVCL_A8EZ | ||
| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
53.4 μM
|
|||
| Administration Time | 15 min | ||||
| Description |
More specifically, compounds 1b and 3b demonstrated significantly higher activity against U87 cells compared to MCF-7 and HT-29 cells (Figure 6). Importantly, 1b was more active than 3b demonstrating that the attached CPP is indeed necessary to increase the overall cellular uptake and thus cytotoxic activity of the conjugates. Of note is also that 2b was less efficient than 1b but marginally more active than 3b, although with no selectivity. For the two conjugates bearing the GFLG motif, it was seen that 3c is still significantly more active in U87 cells expressing integrin receptors. By contrast, 1c kept its selectivity against HT-29 cells, but was pronouncedly more active in MCF-7 cells compared to 1b.
Click to Show/Hide
|
||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cell | CVCL_0031 | ||
References