General Information of This Linker
Linker ID
LIN0VYOTL
Linker Name
TE-VC-PAB
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C23H35N5O6S
Isosmiles
CC([C@H](NC(CCCC(S)=O)=O)C(N[C@@H](CCCNC(N)=O)C(NC1=CC=C(CO)C=C1)=O)=O)C
InChI
InChI=1S/C23H35N5O6S/c1-14(2)20(28-18(30)6-3-7-19(31)35)22(33)27-17(5-4-12-25-23(24)34)21(32)26-16-10-8-15(13-29)9-11-16/h8-11,14,17,20,29H,3-7,12-13H2,1-2H3,(H,26,32)(H,27,33)(H,28,30)(H,31,35)(H3,24,25,34)/t17-,20-/m0/s1
InChIKey
LMEVHJSRYWJFPR-PXNSSMCTSA-N
Pharmaceutical Properties
Molecule Weight
509.629
Polar area
179.72
Complexity
829.2942158
xlogp Value
0.8182
Heavy Count
35
Rot Bonds
15
Hbond acc
6
Hbond Donor
7
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
40151029 ADC 2 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.085 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

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In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.182 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Lung papillary adenocarcinoma NCI-H441 cells CVCL_1561
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.265 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Pancreatic ductal adenocarcinoma BxPC-3 cells CVCL_0186
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.418 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Hypopharyngeal squamous cell carcinoma FaDu cells CVCL_1218
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1.945 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Breast acantholytic squamous cell carcinoma HCC-1806 cells CVCL_1258
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) > 100 nM Negative TROP2 expression (TROP2-)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
40151029 ADC 1 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.144 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.224 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Lung papillary adenocarcinoma NCI-H441 cells CVCL_1561
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.338 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Pancreatic ductal adenocarcinoma BxPC-3 cells CVCL_0186
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.683 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Hypopharyngeal squamous cell carcinoma FaDu cells CVCL_1218
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1.027 nM
Positive TROP2 expression (TROP2+++/++)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Breast acantholytic squamous cell carcinoma HCC-1806 cells CVCL_1258
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) > 100 nM Negative TROP2 expression (TROP2-)
Method Description
Trop2 positive tumor cells FaDu, NCI-N87, BxPC-3, NCI-H441, HCC-1806, and Trop2 negative cell Calu-6 were inoculated into 96-well plates at a quantity of 5000 cells/well in 90 uL of media and incubated overnight at 37 °C in a 5% CO2 cell incubator. Each sample was diluted fivefold with PBS from an initial concentration of 1 mM, total of 9 concentration gradients were tested. 10 uL of each concentration was added into 3 repeat wells, and the 96-well plates were cultured in a cell incubator with 5% CO2 at 37 °C for 144 h. Original culture medium was discarded, 100 uL of CCK-8 solution was added and incubated at 37 °C for 2-4 h, and measured optical density (OD) values at 450 nm. The IC50 values and the cell viability curve were calculated by GraphPad Prism software.

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In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
References
Ref 1 Direct Preparation of Site-Specific Antibody-Drug Conjugates with Unpurified Antibodies in Culture Medium