Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_02027
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| PDC Name |
CPT-Cyclo-GCGPep Conjugate 3
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| PDC Status |
Investigative
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| Indication |
In total 2 Indication(s)
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| Structure |
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| Peptide Name |
Cyclo-GCGPep1
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Peptide Info | ||||
| Drug Name |
Camptothecin
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Drug Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
4-yl 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoate
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Linker Info | ||||
| Peptide Modified Type |
Cyclization modification
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| Modified Segment |
Head-to-tail cyclization
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| Formula |
C93H135N27O22S
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| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 2015.337 | ||||
| Lipid-water partition coefficient (xlogp) | -5.438 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 22 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 30 | |||||
| Rotatable Bond Count (rotbonds) | 40 | |||||
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 | Breast cancer | ||||
| Efficacy Data | Cell viability |
70.00%
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| Administration Time | 48 h | ||||
| Administration Dosage | 10 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
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| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cell | CVCL_0033 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Cell viability |
90.00%
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| Administration Time | 48 h | ||||
| Administration Dosage | 2.5 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
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| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cell | CVCL_0033 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
90.00%
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| Administration Time | 48 h | ||||
| Administration Dosage | 10 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
||||
| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
|
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cell | CVCL_1603 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Cell viability |
98.00%
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| Administration Time | 48 h | ||||
| Administration Dosage | 0.156 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
||||
| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
|
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cell | CVCL_0033 | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Cell viability |
99.00%
|
|||
| Administration Time | 48 h | ||||
| Administration Dosage | 0.625 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
||||
| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
|
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cell | CVCL_0033 | ||
| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
100.00%
|
|||
| Administration Time | 48 h | ||||
| Administration Dosage | 0.156 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
||||
| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
|
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cell | CVCL_1603 | ||
| Experiment 7 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
100.00%
|
|||
| Administration Time | 48 h | ||||
| Administration Dosage | 0.625 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
||||
| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
|
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cell | CVCL_1603 | ||
| Experiment 8 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
100.00%
|
|||
| Administration Time | 48 h | ||||
| Administration Dosage | 2.5 μM | ||||
| Evaluation Method | CCK-8 assay | ||||
| MOA of PDC |
In this research, based on the binding mode between Trastuzumab and HER2 protein, we first discovered a peptide sequence Leadpep that plays a vital role when antibody binds with HER2 protein. In silico mutations were conducted on Leadpep to screen out HER2-targeted peptides. The binding affinity of Cyclo-GCGPep1 increased when cyclized (Kd = 2.555 10-6M). It was used for constructing PDCs with the cytotoxin Camptothecin. Among them, Conjugate 1 showed best antiproliferative activities. Further research demonstrated that Conjugate 1 has a similar mechanism to Camptothecin. It is worth noting that Conjugate 1 showed a good specific delivery capacity and better penetration than Camptothecin. It could be a new therapeutic tool for HER2-positive cancer.
Click to Show/Hide
|
||||
| Description |
Antiproliferative activity of conjugates were evaluated using HER2-positive SK-BR-3 and NCI-N87 cells. As shown in Fig. 5A, Conjugate 1 reduced the cell viability by 23, 38, 47 and 66% at 0.156, 0.625, 2.5 and 10 μM. Its cytotoxicity is significantly more than Conjugate 2 at 0.625 μM and 10 μM. It showed comparable cytotoxicity with CPT at 10 μM. And Conjugate 3 showed little cytotoxicity at any concentrations other than 10 μM, which may be related to the structure of Conjugate 3 where CPT is conjugated on the peptide by non-breakable bond preventing CPT from acting as an anticancer agent. Cyclo-GCGPep1 exhibited no significant cytotoxicity at any concentrations indicating that peptide part of PDCs is inactive for inducing cancer cell death. Similar results can be seen on NCI-N87 cells. Conjugate 1 reduced significantly more cell viability than Conjugate 2 at 0.156 μM and 2.5 μM. And Conjugate 1 exhibited comparable antiproliferation activity as CPT at 2.5 μM and 10 μM. The cytotoxicity of Conjugate 3 is still weak at any concentrations. Cyclo-GCGPep1 is non-toxic to NCI-N87 cells as well. These results told us antiproliferative activity of conjugates is closely related to the ways drugs are conjugated. The cleavable disulfide bonds in Conjugate 1 and 2 could be broken and then Camptothecin derivatives can be released in cells, which is much related to anti-proliferative activity. In general, Conjugate 1 showed best antiproliferative activity and it was selected for further research.
Click to Show/Hide
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cell | CVCL_1603 | ||
References
