Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00051
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| PDC Name |
1131-MMAE
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| PDC Status |
Investigative
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| Indication |
In total 1 Indication(s)
Gastric cancer
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| Structure |
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| Peptide Name |
Peptide 1131
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Peptide Info | ||||
| Receptor Name |
Kita-kyushu lung cancer antigen 1 (CT83)
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Receptor Info | ||||
| Drug Name |
Monomethyl auristatin E
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Drug Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Vc-PABC
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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 |
C108H175N23O30S3
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| #Ro5 Violations (Lipinski): 4 | Molecular Weight | 2371.92 | ||||
| Lipid-water partition coefficient (xlogp) | -1.6044 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 24 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 34 | |||||
| Rotatable Bond Count (rotbonds) | 56 | |||||
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 | Gastric cancer | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3.87 nM
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| Administration Time | 72 h | ||||
| Description |
We next evaluated the in vitro cytotoxicity of 1131-MMAE. NUGC-4, MKN45 and HGC27 cells were drug-treated for 72 h and their viability was assessed. 1131-MMAE killed KK-LC-1 positive gastric cancer cells with high potency. The IC50 values of 1131-MMAE were 3.87 nM for NUGC-4 cells and 5.26 nM for MKN45 cells. However, although a very high concentration was used, 1131-MMAE could only moderately inhibit the viability of KK-LC-1 negative HGC27 cells. The IC50 value of 1131-MMAE for HGC27 cells was 100-200 times higher than that in NUGC-4 and MNK45 cells. Free MMAE exerted cytotoxicity irrespective of the KK-LC-1 expression status. The IC50 values of free MMAE were 10.97 nM for NUGC-4 cells, 10.70 nM for MKN45 cells and 7.18 nM for HGC27 cells. Naked 1131 peptide showed no cytotoxicity to all three cell lines. These results were consistent with the KK-LC-1-dependent endocytosis and confirmed the target-selective killing of 1131-MMAE.
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| In Vitro Model | Gastric signet ring cell adenocarcinoma | NUGC-4 cell | CVCL_3082 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric cancer | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
5.26 nM
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| Administration Time | 72 h | ||||
| Description |
We next evaluated the in vitro cytotoxicity of 1131-MMAE. NUGC-4, MKN45 and HGC27 cells were drug-treated for 72 h and their viability was assessed. 1131-MMAE killed KK-LC-1 positive gastric cancer cells with high potency. The IC50 values of 1131-MMAE were 3.87 nM for NUGC-4 cells and 5.26 nM for MKN45 cells. However, although a very high concentration was used, 1131-MMAE could only moderately inhibit the viability of KK-LC-1 negative HGC27 cells. The IC50 value of 1131-MMAE for HGC27 cells was 100-200 times higher than that in NUGC-4 and MNK45 cells. Free MMAE exerted cytotoxicity irrespective of the KK-LC-1 expression status. The IC50 values of free MMAE were 10.97 nM for NUGC-4 cells, 10.70 nM for MKN45 cells and 7.18 nM for HGC27 cells. Naked 1131 peptide showed no cytotoxicity to all three cell lines. These results were consistent with the KK-LC-1-dependent endocytosis and confirmed the target-selective killing of 1131-MMAE.
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| In Vitro Model | Gastric adenocarcinoma | MKN45 cell | CVCL_0434 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Gastric cancer | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
786 nM
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| Administration Time | 72 h | ||||
| Description |
We next evaluated the in vitro cytotoxicity of 1131-MMAE. NUGC-4, MKN45 and HGC27 cells were drug-treated for 72 h and their viability was assessed. 1131-MMAE killed KK-LC-1 positive gastric cancer cells with high potency. The IC50 values of 1131-MMAE were 3.87 nM for NUGC-4 cells and 5.26 nM for MKN45 cells. However, although a very high concentration was used, 1131-MMAE could only moderately inhibit the viability of KK-LC-1 negative HGC27 cells. The IC50 value of 1131-MMAE for HGC27 cells was 100-200 times higher than that in NUGC-4 and MNK45 cells. Free MMAE exerted cytotoxicity irrespective of the KK-LC-1 expression status. The IC50 values of free MMAE were 10.97 nM for NUGC-4 cells, 10.70 nM for MKN45 cells and 7.18 nM for HGC27 cells. Naked 1131 peptide showed no cytotoxicity to all three cell lines. These results were consistent with the KK-LC-1-dependent endocytosis and confirmed the target-selective killing of 1131-MMAE.
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| In Vitro Model | Gastric carcinoma | HGC-27 cell | CVCL_1279 | ||
References