Peptide Information
General Information of This Peptide
| Peptide ID |
PEP00167
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| Peptide Name |
DT7
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| Structure |
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| Sequence |
HAIYPRH
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| Peptide Type |
Linear
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| Receptor Name |
Transferrin receptor protein 1 (TFRC)
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Receptor Info | ||||
| PDC Transmembrane Types | Cell targeting peptides (CTPs) | |||||
| Formula |
C41H60N14O9
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| Isosmiles |
[H]N/C(N)=N/CCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O[H])cc1)NC(=O)[C@@]([H])(NC(=O)[C@H](C)NC(=O)[C@H](Cc1cn([H])cn1)N[H])[C@@H](C)CC)C(=O)N[C@@H](Cc1cn([H])cn1)C(=O)O
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| InChI |
InChI=1S/C41H60N14O9/c1-4-22(2)33(54-34(57)23(3)50-35(58)28(42)16-25-18-45-20-48-25)38(61)52-30(15-24-9-11-27(56)12-10-24)39(62)55-14-6-8-32(55)37(60)51-29(7-5-13-47-41(43)44)36(59)53-31(40(63)64)17-26-19-46-21-49-26/h9-12,18-23,28-33,56H,4-8,13-17,42H2,1-3H3,(H,45,48)(H,46,49)(H,50,58)(H,51,60)(H,52,61)(H,53,59)(H,54,57)(H,63,64)(H4,43,44,47)/t22-,23-,28-,29-,30-,31-,32-,33-/m0/s1
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| InChIKey |
XAEMVBIKWOMFAH-JIQJDAEYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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893.02
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Polar area
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371.12
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Complexity
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892.4667695
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xlogp Value
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-2.1872
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Heavy Count
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64
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Rot Bonds
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26
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Hbond acc
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12
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Hbond Donor
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12
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The Activity Data of This Peptide
| Peptide Activity Information 1 | [1] | |||||
| KD | 22±1 nM | |||||
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| Binding Affinity Assay |
Recombinant anti-transferrin receptor antibody was captured by the Protein A sensor chip at the concentration of 15 μg/mL with a level of &tide;6000 response units (RU) [28]. Then, the DT7 peptide was dissolved in HBS-EP buffer at a series of defined concentrations (78, 156, 313, and 1250 nM) and injected for recording resonance changes to assess the binding affinity.
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| Experimental Condition | Protein A sensor chip in the vitro | |||||
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
LT7-SS-DOX [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Glioblastoma | ||||
| Efficacy Data | Proliferation inhibitory activity |
41.00%
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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| Description |
Even at an equal DOX concentration of 40 μM, the cell viability of the three types of tumor cells after exposure to this conjugate for 48 h were 41.0%, 61.5%, and 67.2%, respectively.
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| In Vitro Model | Glioblastoma | U87 cell | CVCL_3429 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Hepatoblastoma | ||||
| Efficacy Data | Proliferation inhibitory activity |
61.50%
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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| Description |
Even at an equal DOX concentration of 40 μM, the cell viability of the three types of tumor cells after exposure to this conjugate for 48 h were 41.0%, 61.5%, and 67.2%, respectively.
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| In Vitro Model | Hepatoblastoma | Hep-G2 cell | CVCL_0027 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Lung adenocarcinoma | ||||
| Efficacy Data | Proliferation inhibitory activity |
67.20%
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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| Description |
Even at an equal DOX concentration of 40 μM, the cell viability of the three types of tumor cells after exposure to this conjugate for 48 h were 41.0%, 61.5%, and 67.2%, respectively.
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| In Vitro Model | Lung adenocarcinoma | A-549 cell | CVCL_0023 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Hepatoblastoma | ||||
| Efficacy Data | Proliferation inhibitory activity |
73.10%
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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| Description |
The proliferation inhibitory activity of LT7-SS-DOX was the weakest among the three drugs because the cell viabilities of U87, HepG2, and A549 cells after incubation with LT7-SS-DOX (equal DOX concentration of 20 μM) for 48 h were 95.1%, 73.1%, and 83.2%, respectively.
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| In Vitro Model | Hepatoblastoma | Hep-G2 cell | CVCL_0027 | ||
| Experiment 5 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Lung adenocarcinoma | ||||
| Efficacy Data | Proliferation inhibitory activity |
83.20%
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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| Description |
The proliferation inhibitory activity of LT7-SS-DOX was the weakest among the three drugs because the cell viabilities of U87, HepG2, and A549 cells after incubation with LT7-SS-DOX (equal DOX concentration of 20 μM) for 48 h were 95.1%, 73.1%, and 83.2%, respectively.
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| In Vitro Model | Lung adenocarcinoma | A-549 cell | CVCL_0023 | ||
DT7-SS-DOX [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Glioblastoma | ||||
| Efficacy Data | Proliferation inhibitory activity |
95.10%
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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|
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| Description |
The proliferation inhibitory activity of LT7-SS-DOX was the weakest among the three drugs because the cell viabilities of U87, HepG2, and A549 cells after incubation with LT7-SS-DOX (equal DOX concentration of 20 μM) for 48 h were 95.1%, 73.1%, and 83.2%, respectively.
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| In Vitro Model | Glioblastoma | U87 cell | CVCL_3429 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Glioblastoma | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
5.70 ± 0.22 µM
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
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| Description |
DT7-SS-DOX exhibited good in vitro antiproliferative activity against the three tumor cell lines, with IC50 values of 5.70 ± 0.22 μM (U87), 7.01 ± 1.64 μM (HepG2), and 20.61 ± 4.81 μM (A549), respectively.
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| In Vitro Model | Glioblastoma | U87 cell | CVCL_3429 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Hepatoblastoma | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
7.01 ± 1.64 µM
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
Click to Show/Hide
|
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| Description |
DT7-SS-DOX exhibited good in vitro antiproliferative activity against the three tumor cell lines, with IC50 values of 5.70 ± 0.22 μM (U87), 7.01 ± 1.64 μM (HepG2), and 20.61 ± 4.81 μM (A549), respectively.
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| In Vitro Model | Hepatoblastoma | Hep-G2 cell | CVCL_0027 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Lung adenocarcinoma | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
20.61 ± 4.81 µM
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| Administration Time | 48 h | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX.
Click to Show/Hide
|
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| Description |
DT7-SS-DOX exhibited good in vitro antiproliferative activity against the three tumor cell lines, with IC50 values of 5.70 ± 0.22 μM (U87), 7.01 ± 1.64 μM (HepG2), and 20.61 ± 4.81 μM (A549), respectively.
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| In Vitro Model | Lung adenocarcinoma | A-549 cell | CVCL_0023 | ||
T7-SN-38 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [3] | ||||
| Indication | Glioblastoma | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
70.07nM
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| Administration Time | 72 h | ||||
| Evaluation Method | XTT assay | ||||
| MOA of PDC |
In the present work, the cytotoxic drug SN-38 is coupled to the tumor-targeting T7 peptide via a cathepsin B cleavable VA peptide linker. This ensures that the drug remains covalently bound until it reaches the intended site of action, where Cat B is overexpressed to release the drug. Within this framework, our research pursuits entail the synthesis and characterization of a T7-SN-38-targeted drug conjugate using strain-promoted azide-alkyne cycloaddition (SPAAC). Our investigation extended to evaluating the cellular uptake and assessing the cytotoxicity of the drug conjugate in U87MG glioblastoma cells.
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| Description |
Further, IC50values of SN-38 and T7-SN-38 on U87MG cells at 72 h were determined. An estimated IC50value of 26.41nM was obtained for SN-38, which was considerably lower than an IC50value of 70.07nM obtained for the T7-SN-38 conjugate. These IC50data confirm the greater cytotoxicity of the pure drug compared to the conjugate at 72 h (p< 0.05).
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| In Vitro Model | Glioblastoma | U-87MG cell | CVCL_0022 | ||
References