Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0OHEEX
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| ADC Name |
aZO-ADC-2
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| Synonyms |
AZO-ADC-2
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| Organization |
Beijing Institute of Pharmacology and Toxicology.;Chinese Academy of Medical Sciences & Peking Union Medical College.
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
3.6-4.1
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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 |
Monomethyl auristatin E
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Solubilizing group-PEG2-Hypoxia sensitive linker-Azobenzene
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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ADC-specific functional property(2027 Update)
Bystander Killing Effect
| Bystander Killing Effect | Description | Reference |
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| yes |
To evaluate the bystander effect of AZO-ADC-2, a HER2 + and HER2- cell (SKOV3 and MCF-7) co-culture model was conducted to examine the oxygen controllable bystander effect of AZO-ADC-2.Under hypoxia, AZO-ADC-2 maintained high activity inthe coculture model (EC50 = 0.053 nM).
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[1]
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Payload Release Efficiency
| Incubation Time | 24h | Release | 74.3% | Reference |
[1]
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| Description |
Under Hypoxia + 0.1 mg/mL azoreductase
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| Incubation Time | 24h | Release | 27.49% | Reference |
[1]
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| Description |
Under Hypoxia + 0.05 mg/mL azoreductase
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| Incubation Time | 24h | Release | 14.99% | Reference |
[1]
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| Description |
Under Hypoxia + 0.1 mg/mL azoreductase
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Binding Affinity
| Dissocation Constant (Kd) | Binding Target | Description | Reference |
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| 0.14 ug/mL |
HER2
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The binding affinities ofAZO-ADC-2 and Herceptin for HER2 antigen were comparable, with EC50 values of 0.14 ug/mL and 0.042 ug/mL, respectively (Figure 4h).
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[1]
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Circulating Stability
| Incubation Time | 7days | Release | <1% | Reference |
[1]
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| Incubation Medium | human plasma | ||||
| Description |
AZO-ADC-2 showed a < 1% release ofthe total MMAE payload over 7 days in human plasma.
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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 |
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| Tumor Growth lnhibition value (TGl) |
62.36
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%
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Undisclosed | Undisclosed |
| Tumor Growth lnhibition value (TGl) |
90.97
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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) | 62.36% | Low HER2 expression (HER2+) | ||
| Method Description |
Investigated the antitumour effect of 12 MG/KG AZO-ADC-2 in a Herceptin-resistant, HER2low JIMT-1 xenograft tumour model.
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| In Vivo Model | Herceptin-resistant, HER2-low JIMT-1 xenograft tumour model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 90.97% | High HER2 expression (HER2+++) | ||
| Method Description |
In the HER2high NCI-N87 xenograft model, Herceptin, AZO-ADC-2 and VC-ADC were administered once a week at a dose of 5 or 10 mg/kg for four consecutive weeks. Compared with the control group, AZO-ADC-2 (5 mg/kg) treatment group displayed significant and sustained suppression of tumour growth with an inhibition rate of 90.97 %
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| In Vivo Model | HER2high NCI-N87 xenograft model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.016 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to HER2+ SK-BR-3 cells
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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 Effective Concentration (EC50) | 0.027 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to HER2+ BK474 cells
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| In Vitro Model | Invasive breast carcinoma | BT-474 cells | CVCL_0179 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.053 nM
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| Method Description |
Cytotoxicity of AZO-ADC-2 to SKOV3/MCF-7 co-culture under 0.1% O2
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| In Vitro Model | Ovarian serous cystadenocarcinoma; Invasive breast carcinoma of no special type | SKOV3/MCF-7 co-culture cells | CVCL_0532; CVCL_0031 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.063 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to SKOV-3 cells under 0.1 % O2
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| In Vitro Model | Ovarian serous adenocarcinoma | SKOV-3 cells | CVCL_0532 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.069 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to HER2+ NCI-N87 cells
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.079 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to SKOV-3 cells under 1 % O2
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| In Vitro Model | Ovarian serous adenocarcinoma | SKOV-3 cells | CVCL_0532 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.088 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-0/4/6/8 to SKOV-3 cells under 0.1 % O2
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| In Vitro Model | Ovarian serous adenocarcinoma | SKOV-3 cells | CVCL_0532 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.19 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to BT474-HDR cells under 0.1% O2
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| In Vitro Model | Invasive breast carcinoma of no special type | BT474-HDR cells | CVCL_0179 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.28 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-0/4/6/8 to BT474-HDR cells under 0.1 % O2
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| In Vitro Model | Invasive breast carcinoma of no special type | BT474-HDR cells | CVCL_0179 | ||
| Experiment 10 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 0.57 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to BT474-HDR cells under 1 % O2
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| In Vitro Model | Invasive breast carcinoma of no special type | BT474-HDR cells | CVCL_0179 | ||
| Experiment 11 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 3.74 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to SKOV-3 cells under 5 % O2
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| In Vitro Model | Ovarian serous adenocarcinoma | SKOV-3 cells | CVCL_0532 | ||
| Experiment 12 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 9.12 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to BT474-HDR cells under 5 % O2
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| In Vitro Model | Invasive breast carcinoma of no special type | BT474-HDR cells | CVCL_0179 | ||
| Experiment 13 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 11.05 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-0/4/6/8 toBT474-HDR cells under 20 % O2
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| In Vitro Model | Invasive breast carcinoma of no special type | BT474-HDR cells | CVCL_0179 | ||
| Experiment 14 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 27.67 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-0/4/6/8 to SKOV-3 cells under 20 % O2
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| In Vitro Model | Ovarian serous adenocarcinoma | SKOV-3 cells | CVCL_0532 | ||
| Experiment 15 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 66.8 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to SKOV-3 cells under 20 % O2
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| In Vitro Model | Ovarian serous adenocarcinoma | SKOV-3 cells | CVCL_0532 | ||
| Experiment 16 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 109.1 nM | High HER2 expression (HER2+++) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to BT474-HDR cells under 20 % O2
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| In Vitro Model | Invasive breast carcinoma of no special type | BT474-HDR cells | CVCL_0179 | ||
| Experiment 17 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 115.4 nM | Low HER2 expression (HER2+) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to HER2- MCF-7 cells
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| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 18 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
134.7 nM
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| Method Description |
Cytotoxicity of AZO-ADC-2 to SKOV3/MCF-7 co-culture under 20% O2
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| In Vitro Model | Ovarian serous cystadenocarcinoma; Invasive breast carcinoma of no special type | SKOV3/MCF-7 co-culture cells | CVCL_0532; CVCL_0031 | ||
| Experiment 19 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
266.93 nM
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| Method Description |
Cytotoxicity of AZO-ADC-2 to normal cells, LO2 cells
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| In Vitro Model | Human papillomavirus-related endocervical adenocarcinoma | LO2 cells | CVCL_6926 | ||
| Experiment 20 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | > 666 nM | Low HER2 expression (HER2+) | ||
| Method Description |
Cytotoxicity of AZO-ADC-2 to HER2- MDA-MB-231 cells
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 21 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | > 666 nM | |||
| Method Description |
Cytotoxicity of AZO-ADC-2 to normal cells, NIH3T3 cells
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| In Vitro Model | Normal | NIH3T3 cells | CVCL_0594 | ||
| Experiment 22 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | > 666 nM | |||
| Method Description |
Cytotoxicity of AZO-ADC-2 to normal cells, 293T cells
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| In Vitro Model | Normal | 293T cells | CVCL_0063 | ||
References