Linker Information
General Information of This Linker
| Linker ID |
LIN00148
|
|||||
|---|---|---|---|---|---|---|
| Linker Name |
2-Disulfaneylethyl hydrogen carbonate
|
|||||
| Linker Type |
GSH concentration-sensitive linkers
|
|||||
| Structure |
|
|||||
| Formula |
C3H6O3S2
|
|||||
| #Ro5 Violations (Lipinski): 0 | Molecular Weight (mw) | 154.212 | ||||
| Lipid-water partition coefficient (xlogp) | 1.259 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 2 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 4 | |||||
| Rotatable Bond Count (rotbonds) | 3 | |||||
| Canonical smiles |
O=C(O)OCCSS
|
|||||
| InChI |
InChI=1S/C3H6O3S2/c4-3(5)6-1-2-8-7/h7H,1-2H2,(H,4,5)
|
|||||
| InChIKey |
GIRKPUUKWCSTPG-UHFFFAOYSA-N
|
|||||
Each Peptide-drug Conjugate Related to This Linker
Full Information of The Activity Data of The PDC(s) Related to This Linker
CPT-Cyclo-GCGPep Conjugate 1 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Cell viability |
33.00%
|
|||
| 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 | Breast adenocarcinoma | SK-BR-3 cell | CVCL_0033 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
44.00%
|
|||
| 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 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Cell viability |
53.00%
|
|||
| 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 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
53.00%
|
|||
| 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 | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Cell viability |
61.00%
|
|||
| 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 | Breast cancer | ||||
| Efficacy Data | Cell viability |
76.00%
|
|||
| 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 7 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric tubular adenocarcinoma | ||||
| Efficacy Data | Cell viability |
82.00%
|
|||
| 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 |
85.00%
|
|||
| 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 | ||
References