Linker Information
General Information of This Linker
| Linker ID |
LIN0PJPWF
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|---|---|---|---|---|---|---|
| Linker Name |
aHer2- (BL1-LP1)<sub>7.7</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 |
C112H168N20O28
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| Isosmiles |
CC([C@H](NC(CCOCCOCCOCCOCCNC(COC1CCCCCC2=C1C(C)=NN=C2C3=CC=C(C=C3)CNC(CN(CC(NCC4=CC=C(C5=NN=C(C)C6=C5CCCCCC6OCC(NCCOCCOCCOCCOCCC(N[C@@H](C(C)C)C(N[C@@H](CCCNC(N)=O)C(NC7=CC=C(C=C7)CO)=O)=O)=O)=O)C=C4)=O)CCOCCOCCOCCNC(C)=O)=O)=O)=O)C(N[C@@H](CCCNC(N)=O)C(NC8=CC=C(C=C8)CO)=O)=O)C
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| InChI |
InChI=1S/C112H168N20O28/c1-76(2)103(109(144)124-91(18-14-40-118-111(113)146)107(142)122-87-34-26-83(72-133)27-35-87)126-95(136)38-46-148-52-58-154-64-66-157-61-55-151-49-43-116-99(140)74-159-93-20-12-8-10-16-89-101(93)78(5)128-130-105(89)85-30-22-81(23-31-85)68-120-97(138)70-132(45-51-153-57-63-156-60-54-150-48-42-115-80(7)135)71-98(139)121-69-82-24-32-86(33-25-82)106-90-17-11-9-13-21-94(102(90)79(6)129-131-106)160-75-100(141)117-44-50-152-56-62-158-67-65-155-59-53-149-47-39-96(137)127-104(77(3)4)110(145)125-92(19-15-41-119-112(114)147)108(143)123-88-36-28-84(73-134)29-37-88/h22-37,76-77,91-94,103-104,133-134H,8-21,38-75H2,1-7H3,(H,115,135)(H,116,140)(H,117,141)(H,120,138)(H,121,139)(H,122,142)(H,123,143)(H,124,144)(H,125,145)(H,126,136)(H,127,137)(H3,113,118,146)(H3,114,119,147)/t91-,92-,93?,94?,103-,104-/m0/s1
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| InChIKey |
KJBUUQGCIUTNDE-MRZJIELMSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2242.688
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Polar area
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645.59
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Complexity
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.
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xlogp Value
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4.54194
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Heavy Count
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160
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Rot Bonds
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80
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Hbond acc
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33
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Hbond Donor
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17
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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- (BL1-LP1)7.7 [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) |
0.16 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) |
0.282 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) |
0.682 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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|
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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) |
366 nM
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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- (BL1-LP1)7.6 [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) |
89.1 nM
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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) |
142 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 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
210 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 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
331 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