Linker Information
General Information of This Linker
| Linker ID |
LIN00008
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| Linker Name |
Mc-Vc-PABC
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| Linker Type |
Enzyme-sensitive linkers
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| Structure |
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| Formula |
C29H42N6O9S
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| #Ro5 Violations (Lipinski): 3 | Molecular Weight (mw) | 650.7 | ||||
| Lipid-water partition coefficient (xlogp) | 0.8 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 7 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 10 | |||||
| Rotatable Bond Count (rotbonds) | 19 | |||||
| PubChem CID | ||||||
| Canonical smiles |
CC(C)C(C(=O)NC(CCCNC(=O)N)C(=O)NC1=CC=C(C=C1)COC(=O)O)NC(=O)CCCCCN2C(=O)CC(C2=O)S
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| InChI |
InChI=1S/C29H42N6O9S/c1-17(2)24(34-22(36)8-4-3-5-14-35-23(37)15-21(45)27(35)40)26(39)33-20(7-6-13-31-28(30)41)25(38)32-19-11-9-18(10-12-19)16-44-29(42)43/h9-12,17,20-21,24,45H,3-8,13-16H2,1-2H3,(H,32,38)(H,33,39)(H,34,36)(H,42,43)(H3,30,31,41)/t20-,21?,24?/m0/s1
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| InChIKey |
LEBKZSAGLVOOHK-MFMCRYCZSA-N
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| IUPAC Name |
[4-[[(2S)-5-(carbamoylamino)-2-[[2-[6-(2,5-dioxo-3-sulfanylpyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl hydrogen carbonate
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Each Peptide-drug Conjugate Related to This Linker
Full Information of The Activity Data of The PDC(s) Related to This Linker
1131-MMAE [Investigative]
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