Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00404
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| PDC Name |
Lytic peptides 6 - Paclitaxel conjugate
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| PDC Status |
Investigative
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| Indication |
In total 5 Indication(s)
Chronic myeloid leukemia
Invasive breast carcinoma
Invasive ductal carcinoma
Ovarian endometrioid adenocarcinoma
Ovarian serous cystadenocarcinoma
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| Structure |
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| Peptide Name |
Lytic peptides 6
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Peptide Info | ||||
| Drug Name |
Paclitaxel
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Drug Info | ||||
| Therapeutic Target |
Microtubule (MT)
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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 | ||||
| Formula |
C169H255N45O35S
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| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 3509.246 | ||||
| Lipid-water partition coefficient (xlogp) | -3.16546 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 40 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 45 | |||||
| Rotatable Bond Count (rotbonds) | 103 | |||||
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 | Invasive breast carcinoma | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
1.98 ± 0.14 μM
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| Administration Time | 48 h | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.
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| Description |
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.
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| In Vitro Model | Invasive breast carcinoma | MCF-7 cell | CVCL_0031 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Ovarian endometrioid adenocarcinoma | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
2.79 ± 0.17 μM
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| Administration Time | 48 h | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.
Click to Show/Hide
|
||||
| Description |
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.
Click to Show/Hide
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| In Vitro Model | Ovarian endometrioid adenocarcinoma | A2780 cell | CVCL_0134 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Chronic myeloid leukemia | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
3.82 ± 0.29 μM
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| Administration Time | 48 h | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.
Click to Show/Hide
|
||||
| Description |
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.
Click to Show/Hide
|
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| In Vitro Model | Chronic myeloid leukemia | K562 cell | CVCL_0004 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Invasive ductal carcinoma | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
5.53 ± 0.76 μM
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| Administration Time | 48 h | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.
Click to Show/Hide
|
||||
| Description |
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.
Click to Show/Hide
|
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| In Vitro Model | Invasive ductal carcinoma | MCF7/PTX cell | CVCL_C5RS | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Ovarian serous cystadenocarcinoma | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
6.61 ± 0.94 μM
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| Administration Time | 48 h | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.
Click to Show/Hide
|
||||
| Description |
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.
Click to Show/Hide
|
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| In Vitro Model | Ovarian serous cystadenocarcinoma | SK-OV-3 cell | CVCL_0532 | ||
| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
37.22 ± 2.36 μM
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| Administration Time | 48 h | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.
Click to Show/Hide
|
||||
| Description |
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.
Click to Show/Hide
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| In Vitro Model | Normal | Human umbilical vein endothelial cells | Homo sapiens | ||
References