Linker Information
General Information of This Linker
| Linker ID |
LIN0IMHUQ
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|---|---|---|---|---|---|---|
| Linker Name |
aHer2- (AL7-LP13)<sub>7.3</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 |
C98H149N19O30
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| Isosmiles |
CC1=NN=C(C2=C1C(OCC(NCCOCCOCCC(NC(COCCC(NCCOCCOCCC(N[C@@H](CCC(O)=O)C(N[C@H](C(N[C@@H](CCCNC(N)=O)C(NC3=CC=C(C=C3)CO)=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)=O)CCCCC2)C5=CC=C(C=C5)CNC(C)=O
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| InChI |
InChI=1S/C98H149N19O30/c1-62(2)88(95(135)112-74(13-10-37-104-97(99)137)91(131)108-70-24-18-67(57-118)19-25-70)114-93(133)76(28-30-85(127)128)110-82(124)35-43-140-51-53-142-47-39-101-79(121)32-45-145-59-72(107-81(123)34-42-139-50-55-144-49-41-103-84(126)61-147-78-15-9-7-8-12-73-87(78)64(5)116-117-90(73)69-22-16-66(17-23-69)56-106-65(6)120)60-146-46-33-80(122)102-40-48-143-54-52-141-44-36-83(125)111-77(29-31-86(129)130)94(134)115-89(63(3)4)96(136)113-75(14-11-38-105-98(100)138)92(132)109-71-26-20-68(58-119)21-27-71/h16-27,62-63,72,74-78,88-89,118-119H,7-15,28-61H2,1-6H3,(H,101,121)(H,102,122)(H,103,126)(H,106,120)(H,107,123)(H,108,131)(H,109,132)(H,110,124)(H,111,125)(H,112,135)(H,113,136)(H,114,133)(H,115,134)(H,127,128)(H,129,130)(H3,99,104,137)(H3,100,105,138)/t74-,75-,76-,77-,78?,88-,89-/m0/s1
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| InChIKey |
IFLQJUBZKZMGHC-TWTMFIABSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2073.373
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Polar area
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712.45
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Complexity
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.
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xlogp Value
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0.28842
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Heavy Count
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147
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Rot Bonds
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76
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Hbond acc
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30
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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- (AL7-LP13)7.3 [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) |
0.123 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) |
0.216 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) |
0.648 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 | ||
FelD1- (AL7-LP13)7.3 [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) | > 400 nM | Positive HER2expression (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) | > 400 nM | Positive HER2expression (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 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 400 nM | Positive HER2expression (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 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