General Information of This Peptide-drug Conjugate (PDC)
PDC ID
PDC_02027
PDC Name
CPT-Cyclo-GCGPep Conjugate 3
PDC Status
Investigative
Indication
In total 2 Indication(s)
Gastric tubular adenocarcinoma
Breast cancer
Structure
Peptide Name
Cyclo-GCGPep1
 Peptide Info 
Drug Name
Camptothecin
 Drug Info 
Therapeutic Target
DNA topoisomerase 1 (TOP1)
 Target Info 
Linker Name
4-yl 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoate
 Linker Info 
Peptide Modified Type
Cyclization modification
Modified Segment
Head-to-tail cyclization
Formula
C93H135N27O22S
#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
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Cell viability
70.00%
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.

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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
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%
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
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%
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
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%
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
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
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
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
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
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cell CVCL_1603
References
Ref 1 A designed cyclic peptide based on Trastuzumab used to construct peptide-drug conjugates for its HER2-targeting ability. Bioorg Chem. 2021 Dec;117:105453. doi: 10.1016/j.bioorg.2021.105453. Epub 2021 Oct 26.