Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00083
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| PDC Name |
CPT-AAM-2
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| PDC Status |
Investigative
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| Indication |
In total 1 Indication(s)
Melanoma
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| Structure |
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| Peptide Name |
AAM-2
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Peptide Info | ||||
| Receptor Name |
Cell membrane
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| Drug Name |
Camptothecin
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Drug Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
2-(Disulfanyl)ethyl hydrogen carbonate
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Linker Info | ||||
| Formula |
C155H224N42O37S2
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| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 3331.888 | ||||
| Lipid-water partition coefficient (xlogp) | -4.1641 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 37 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 47 | |||||
| Rotatable Bond Count (rotbonds) | 99 | |||||
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 | Melanoma | ||||
| Efficacy Data | Cell survival rate |
55%
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| Administration Time | 72 h | ||||
| Administration Dosage | 10 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
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| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
57%
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| Administration Time | 72 h | ||||
| Administration Dosage | 5 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
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| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
74%
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| Administration Time | 72 h | ||||
| Administration Dosage | 2.5 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
||||
| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
86%
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| Administration Time | 72 h | ||||
| Administration Dosage | 1.25 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
||||
| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
94%
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| Administration Time | 72 h | ||||
| Administration Dosage | 0.625 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
||||
| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
References