Linker Information
General Information of This Linker
| Linker ID |
LIN0ZTLFZ
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| Linker Name |
aHer2- (AL4c-LP13C)<sub>7.07</sub> Linker
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| Linker Type |
Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C100H153N19O31
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| Isosmiles |
CC1=NN=C(C2=CC=C(CC(NC(COCCC(NCCOCCOCCC(N[C@@H](CCC(O)=O)C(N[C@H](C(N[C@@H](CCCNC(N)=O)C(NC(C=C3)=CC=C3CO)=O)=O)C(C)C)=O)=O)=O)COCCC(NCCOCCOCCC(N[C@@H](CCC(O)=O)C(N[C@H](C(N[C@@H](CCCNC(N)=O)C(NC4=CC=C(C=C4)CO)=O)=O)C(C)C)=O)=O)=O)=O)C=C2)C5=C1C(OCC(NCCOCCOCCOCCNC(C)=O)=O)CCCCC5
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| InChI |
InChI=1S/C100H153N19O31/c1-64(2)90(97(137)114-76(13-10-36-107-99(101)139)93(133)110-72-24-18-69(59-120)19-25-72)116-95(135)78(28-30-87(129)130)112-83(125)34-42-141-50-52-144-47-39-104-81(123)32-44-148-61-74(109-85(127)58-68-16-22-71(23-17-68)92-75-12-8-7-9-15-80(89(75)66(5)118-119-92)150-63-86(128)106-41-49-146-55-57-147-56-54-143-46-38-103-67(6)122)62-149-45-33-82(124)105-40-48-145-53-51-142-43-35-84(126)113-79(29-31-88(131)132)96(136)117-91(65(3)4)98(138)115-77(14-11-37-108-100(102)140)94(134)111-73-26-20-70(60-121)21-27-73/h16-27,64-65,74,76-80,90-91,120-121H,7-15,28-63H2,1-6H3,(H,103,122)(H,104,123)(H,105,124)(H,106,128)(H,109,127)(H,110,133)(H,111,134)(H,112,125)(H,113,126)(H,114,137)(H,115,138)(H,116,135)(H,117,136)(H,129,130)(H,131,132)(H3,101,107,139)(H3,102,108,140)/t76-,77-,78-,79-,80?,90-,91-/m0/s1
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| InChIKey |
HARCVHWBQFOAGZ-LTFNDSBSSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2117.426
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Polar area
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721.68
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Complexity
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.
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xlogp Value
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-0.04258
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Heavy Count
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150
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Rot Bonds
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79
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Hbond acc
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31
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Hbond Donor
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21
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
aHer2- (AL4c-LP13C)7.07 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.106 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 1000/well SK-BR-3 cells in 80 uL media (target positive cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.241 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 1000/well Calu-3 in 80 uL media (target positive cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
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| In Vitro Model | Lung adenocarcinoma | Calu-3 cells | CVCL_0609 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.638 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 1000/well NCI-N87 cells in 80 uL media (target positive cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 400 nM | Negative HER2 expression (HER2-) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 800/well NCI-H1975 cells in 80ul media (target negative cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
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| In Vitro Model | Lung adenocarcinoma | NCI-H1975 cells | CVCL_1511 | ||
aHer2- (AL4c-LP13C)7.11 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
13.3 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 1000/well SK-BR-3 cells in 80 uL media (target positive cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
Click to Show/Hide
|
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
24.6 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 1000/well Calu-3 in 80 uL media (target positive cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
Click to Show/Hide
|
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| In Vitro Model | Lung adenocarcinoma | Calu-3 cells | CVCL_0609 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
49.3 nM
|
Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 1000/well NCI-N87 cells in 80 uL media (target positive cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
Click to Show/Hide
|
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 400 nM | Negative HER2 expression (HER2-) | ||
| Method Description |
Cells were seeded in their growth media into 96 well plates (Thermo #136101) one day prior to adding ADCs: 800/well NCI-H1975 cells in 80ul media (target negative cells). 20ul assay media diluted ADC/ isotype conjugates (1:4 10 pts starting from 100uM) as well as free drug were transferred to above cells. The plates were incubated at 37°C, 5% CO2 for 6 days.
Click to Show/Hide
|
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| In Vitro Model | Lung adenocarcinoma | NCI-H1975 cells | CVCL_1511 | ||
References