Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0WQFPM
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| ADC Name |
wO2024222841A1 ADC38
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| Synonyms |
ADC38
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| Organization |
CSPC MEGALITH BIOPHARMACEUTICAL CO.,LTD.
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
7.6
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| Structure |
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| Antibody Name |
Trastuzumab
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Antibody Info | ||||
| Antigen Name |
Receptor tyrosine-protein kinase erbB-2 (ERBB2)
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Antigen Info | ||||
| Payload Name |
(S)B19
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Payload Info | ||||
| Therapeutic Target |
Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1)
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Target Info | ||||
| Linker Name |
OXDc-VA-PAB (PEG)
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
LD38
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ADC-specific functional property(2027 Update)
Payload Release Efficiency
| Incubation Time | 7days | Release | 0.007% | Reference |
[1]
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| Description |
The pharmacokinetic behaviors of the investigational compounds ADC38-4, ADC38, T-ADC-2, and Enhertu were studied in rats after a single intravenous injection of 6 mg/kg. The ADC compounds were administered via tail vein injection at a dose of 6 mg/kg. Blood samples were collected from the retro-orbital sinus before dosing and at 0.5 h, 18 h, 24 h, 48 h, 96 h, and 168 h post-dose. The blood was drawn into citrate tubes and processed to plasma. The content of the antibody-drug conjugates (ADC) in the blood samples was determined by enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated using a non-compartmental model. The content of free small molecules in the blood samples was determined using LC-MS/MS, and pharmacokinetic parameters were also calculated.
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 55.21 | h*nmol/mL |
The pharmacokinetic behaviors of the investigational compounds ADC38-4, ADC38, T-ADC-2, and Enhertu were studied in rats after a single intravenous injection of 6 mg/kg. The ADC compounds were administered via tail vein injection at a dose of 6 mg/kg. Blood samples were collected from the retro-orbital sinus before dosing and at 0.5 h, 18 h, 24 h, 48 h, 96 h, and 168 h post-dose. The blood was drawn into citrate tubes and processed to plasma. The content of the antibody-drug conjugates (ADC) in the blood samples was determined by enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated using a non-compartmental model. The content of free small molecules in the blood samples was determined using LC-MS/MS, and pharmacokinetic parameters were also calculated.
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 55.21 | h*nmol/mL |
The pharmacokinetic behaviors of the investigational compounds ADC38-4, ADC38, T-ADC-2, and Enhertu were studied in rats after a single intravenous injection of 6 mg/kg. The ADC compounds were administered via tail vein injection at a dose of 6 mg/kg. Blood samples were collected from the retro-orbital sinus before dosing and at 0.5 h, 18 h, 24 h, 48 h, 96 h, and 168 h post-dose. The blood was drawn into citrate tubes and processed to plasma. The content of the antibody-drug conjugates (ADC) in the blood samples was determined by enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated using a non-compartmental model. The content of free small molecules in the blood samples was determined using LC-MS/MS, and pharmacokinetic parameters were also calculated.
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 55.21 | h*nmol/mL |
The pharmacokinetic behaviors of the investigational compounds ADC38-4, ADC38, T-ADC-2, and Enhertu were studied in rats after a single intravenous injection of 6 mg/kg. The ADC compounds were administered via tail vein injection at a dose of 6 mg/kg. Blood samples were collected from the retro-orbital sinus before dosing and at 0.5 h, 18 h, 24 h, 48 h, 96 h, and 168 h post-dose. The blood was drawn into citrate tubes and processed to plasma. The content of the antibody-drug conjugates (ADC) in the blood samples was determined by enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated using a non-compartmental model. The content of free small molecules in the blood samples was determined using LC-MS/MS, and pharmacokinetic parameters were also calculated.
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 55.21 | h*nmol/mL |
The pharmacokinetic behaviors of the investigational compounds ADC38-4, ADC38, T-ADC-2, and Enhertu were studied in rats after a single intravenous injection of 6 mg/kg. The ADC compounds were administered via tail vein injection at a dose of 6 mg/kg. Blood samples were collected from the retro-orbital sinus before dosing and at 0.5 h, 18 h, 24 h, 48 h, 96 h, and 168 h post-dose. The blood was drawn into citrate tubes and processed to plasma. The content of the antibody-drug conjugates (ADC) in the blood samples was determined by enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated using a non-compartmental model. The content of free small molecules in the blood samples was determined using LC-MS/MS, and pharmacokinetic parameters were also calculated.
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[1] |
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
| Standard Type | Value | Units | Cell Line | Disease Model |
|---|---|---|---|---|
| Tumor Growth lnhibition value (TGl) |
88
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%
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Undisclosed | Undisclosed |
| Tumor Growth lnhibition value (TGl) |
95
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%
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Undisclosed | Undisclosed |
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 88% | High HER2 expression (HER2+++) | ||
| Method Description |
Investigated the antitumour effect of 3mg/kg ADC in a HER2high HCC-1954 xenograft NUNU mice tumour model, D21.
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| In Vivo Model | HER2-high HCC-1954 xenograft NUNU mice tumour model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 95% | Low HER2 expression (HER2+) | ||
| Method Description |
Investigated the antitumour effect of 5mg/kg ADC in a HER2low JIMT-1 xenograft NUNU mice tumour model, D13.
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| In Vivo Model | HER2-low JIMT-1 xenograft NUNU mice tumour 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) | 0.8 pM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of ADC to BT-474 cells
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| In Vitro Model | Invasive breast carcinoma | BT-474 cells | CVCL_0179 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 25 pM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of ADC to SK-BR-3 cells
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.01676 nM | Low HER2 expression (HER2+) | ||
| Method Description |
Cytotoxicity of ADC to T-47D cells
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| In Vitro Model | Invasive breast carcinoma of no special type | T-47D cells | CVCL_0553 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.4645 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of ADC to NCI-N87 cells
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||