Linker Information
General Information of This Linker
| Linker ID |
LIN0UZNKK
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| Linker Name |
WO2023232144A1, ADC-1, linker
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| Linker Type |
Beta-glucuronide based linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C38H57N9O17
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| Isosmiles |
CC([C@H](NC(CNC(CNC(CNC([C@@H]1[C@@H](O)C(O)[C@H](O)[C@H](O[C@@H]([C@H](O)[C@@H](N=C2C)[C@@H](O2)O3)[C@H]3CO)O1)=O)=O)=O)=O)C(N[C@@H](CCCN([H])C(N)=O)C(NC4=CC=C(C=C4)CO)=O)=O)C
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| InChI |
InChI=1S/C38H57N9O17/c1-16(2)25(34(58)46-20(5-4-10-40-38(39)60)33(57)45-19-8-6-18(14-48)7-9-19)47-24(52)13-42-22(50)11-41-23(51)12-43-35(59)32-29(55)28(54)30(56)37(64-32)63-31-21(15-49)62-36-26(27(31)53)44-17(3)61-36/h6-9,16,20-21,25-32,36-37,48-49,53-56H,4-5,10-15H2,1-3H3,(H,41,51)(H,42,50)(H,43,59)(H,45,57)(H,46,58)(H,47,52)(H3,39,40,60)/t20-,21+,25-,26+,27+,28?,29-,30-,31+,32-,36-,37+/m0/s1
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| InChIKey |
MVOWKUAXCVXPOL-APRRQQRWSA-N
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| Pharmaceutical Properties |
Molecule Weight
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911.92
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Polar area
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400.38
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Complexity
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1752.213866
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xlogp Value
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-6.3718
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Heavy Count
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64
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Rot Bonds
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21
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Hbond acc
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18
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Hbond Donor
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14
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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
wO2023232144A1ADC-1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) |
115.07%
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Positive ErbB2/HER2 expression (ErbB2/HER2+++/++) | ||
| Method Description |
In the ErbB2/HER2 high expression NCI-N87 CDX xenograft model, ADC-1 was administered at a dose of 3 mg/kg for five consecutive weeks. Compared with the control group, ADC-1 treatment group displayed significant suppression of tumour growth with an TGI of 115.07 % and T/C of 6.57%.
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| In Vivo Model | High ErbB2/HER2 expression NCI-N87 CDX xenograft model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.04636 nM
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Positive ErbB2/HER2 expression (ErbB2/HER2+++/++) | ||
| Method Description |
The ErbB2/HER2 positive cells were cultured overnight with ADC-1 or antibody mAb-1 at different concentrations (10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015, 0.00051nM) Or different concentrations of MMAE (monomethyloratin E) (30, 10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015nM); The ErbB2/HER2 negative cells cultured overnight were added with ADC-1 or antibody mAb-1 at different concentrations (100, 10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015nM) Or different concentrations of MMAE (30, 10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015nM); Puromycin with a final concentration of 5uM was added to the control group. Continue warming at 37°C for 72~120h. 3) Remove the cell plates from the 37°C cell incubator and balance for about 30 minutes to room temperature. Each well is supplemented with 100uLCellTiter Glo reagent, the oscillator oscillates for 2min and then stands at room temperature for 10min away from light. The luminescence value (RLU) is measured.
Click to Show/Hide
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| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.08706 nM
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Positive ErbB2/HER2 expression (ErbB2/HER2+++/++) | ||
| Method Description |
The ErbB2/HER2 positive cells were cultured overnight with ADC-1 or antibody mAb-1 at different concentrations (10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015, 0.00051nM) Or different concentrations of MMAE (monomethyloratin E) (30, 10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015nM); The ErbB2/HER2 negative cells cultured overnight were added with ADC-1 or antibody mAb-1 at different concentrations (100, 10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015nM) Or different concentrations of MMAE (30, 10, 3.3, 1.1, 0.37, 0.12, 0.041, 0.014, 0.0046, 0.0015nM); Puromycin with a final concentration of 5uM was added to the control group. Continue warming at 37°C for 72~120h. 3) Remove the cell plates from the 37°C cell incubator and balance for about 30 minutes to room temperature. Each well is supplemented with 100uLCellTiter Glo reagent, the oscillator oscillates for 2min and then stands at room temperature for 10min away from light. The luminescence value (RLU) is measured.
Click to Show/Hide
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wO2023232144A1ADC-4 [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) |
0.09995 nM
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High TROP2 expression (TROP2 +++) | ||
| Method Description |
Cytotoxicity of ADC-2 to BxPC-3 cells
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| In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 cells | CVCL_0186 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.1297 nM
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High TROP2 expression (TROP2 +++) | ||
| Method Description |
Cytotoxicity of ADC to FaDu cells
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| In Vitro Model | Hypopharyngeal squamous cell carcinoma | FaDu cells | CVCL_1218 | ||
References