Linker Information
General Information of This Linker
| Linker ID |
LIN0QAKBX
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| Linker Name |
Uncleavable linker
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| Antibody-Linker Relation |
Uncleavable
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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
SHR-A1403 [Phase 1]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03856541 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1, open label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of SHR-a1403 with intravenous infusion in patients with advanced solid tumors.
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Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 95.50% (Day 17) | High MET expression (MET+++) | ||
| Method Description |
HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (1 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
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| In Vivo Model | Hepatic cancer PDX model (PDX: HCC) | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.30% (Day 17) | High MET expression (MET+++) | ||
| Method Description |
HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (3 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
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| In Vivo Model | Hepatic cancer PDX model (PDX: HCC) | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.50% (Day 17) | High MET expression (MET+++) | ||
| Method Description |
HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (10 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
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| In Vivo Model | Hepatic cancer PDX model (PDX: HCC) | ||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 0.00% (Day 16) | Negative MET expression (MET-) | ||
| Method Description |
Effects of SHR-A1403 were further determined in vivo by assessing the growth of HCC827 and HA1 xenograft tumors. Tumor-bearing mice,established by s.c. inoculation of HCC827 and HA1 cells,were randomized into vehicle,AZD9291 (3 mg/kg single dose,i.g.) and SHR-A1403 (10 mg/kg single dose,i.v.) treatment groups when average tumor volumes reached approximately 100-200 mm3.
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| In Vivo Model | Non-small cell lung cancer HCC827 CDX model (CDX: HA1; Afatinib resistant) | ||||
| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Afatinib resistant; HA1) | CVCL_2063 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 34.50% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.
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| In Vivo Model | Hepatic cancer CDX model | ||||
| In Vitro Model | Adult hepatocellular carcinoma | HCCLM3 cells | CVCL_6832 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 41.80% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.
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| In Vivo Model | Lung cancer CDX model | ||||
| In Vitro Model | Lung cancer | Lung cancer cells | Homo sapiens | ||
| Experiment 4 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 42.80% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.
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| In Vivo Model | Gastric cancer CDX model | ||||
| In Vitro Model | Gastric cancer | Gastric cancer cells | Homo sapiens | ||
| Experiment 5 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 59.30% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.
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| In Vivo Model | Lung cancer CDX model | ||||
| In Vitro Model | Lung cancer | Lung cancer cells | Homo sapiens | ||
| Experiment 6 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 83.30% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.
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| In Vivo Model | Hepatic cancer CDX model | ||||
| In Vitro Model | Adult hepatocellular carcinoma | HCCLM3 cells | CVCL_6832 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 84.60% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.
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| In Vivo Model | Gastric cancer CDX model | ||||
| In Vitro Model | Gastric adenocarcinoma | MKN45 cells | CVCL_0434 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 89.90% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.
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| In Vivo Model | Gastric cancer CDX model | ||||
| In Vitro Model | Gastric adenocarcinoma | MKN45 cells | CVCL_0434 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 91.60% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.
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| In Vivo Model | Lung cancer CDX model | ||||
| In Vitro Model | Lung adenocarcinoma | NCI-H1993 cells | CVCL_1512 | ||
| Experiment 10 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 92.80% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
Effects of SHR-A1403 were further determined in vivo by assessing the growth of HCC827 and HA1 xenograft tumors. Tumor-bearing mice,established by s.c. inoculation of HCC827 and HA1 cells,were randomized into vehicle,AZD9291 (3 mg/kg single dose,i.g.) and SHR-A1403 (10 mg/kg single dose,i.v.) treatment groups when average tumor volumes reached approximately 100-200 mm3.
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| In Vivo Model | Non-small cell lung cancer CDX model | ||||
| In Vitro Model | Lung adenocarcinoma | HCC827 cells | CVCL_2063 | ||
| Experiment 11 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.80% (Day 21) | High MET expression (MET+++) | ||
| Method Description |
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.
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| In Vivo Model | Hepatic cancer CDX model | ||||
| In Vitro Model | Adult hepatocellular carcinoma | HCCLM3 cells | CVCL_6832 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3.20 ng/mL
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High MET expression (MET+++; IHC 3+) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Adult hepatocellular carcinoma | HCCLM3 cells | CVCL_6832 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
7.80 ng/mL
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Negative MET expression (MET-) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Gastric adenocarcinoma | MKN45 cells | CVCL_0434 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
11.80 ng/mL
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Moderate MET expression (MET++) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Afatinib resistant; HA1) | CVCL_2063 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
16.30 ng/mL
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High MET expression (MET+++) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Lung adenocarcinoma | NCI-H1993 cells | CVCL_1512 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
17.80 ng/mL
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High MET expression (MET+++) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Gefitinib resistant) | CVCL_2063 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
26.60 ng/mL
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Negative MET expression (MET-) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Gefitinib resistant) | CVCL_2063 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
46.70 ng/mL
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Moderate MET expression (MET++) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Lung papillary adenocarcinoma | NCI-H441 cells | CVCL_1561 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
53.90 ng/mL
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High MET expression (MET+++; IHC 3+) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Invasive breast carcinoma | Hs 578T cells | CVCL_0332 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
78.20 ng/mL
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High MET expression (MET+++) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Prostate carcinoma | PC-3 cells | CVCL_0035 | ||
| Experiment 10 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
99.40 ng/mL
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Moderate MET expression (MET++) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Gefitinib resistant) | CVCL_2063 | ||
| Experiment 11 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
130.80 ng/mL
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High MET expression (MET+++) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Gefitinib resistant) | CVCL_2063 | ||
| Experiment 12 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
214.80 ng/mL
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Moderate MET expression (MET++) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Clear cell renal cell carcinoma | Caki-1 cells | CVCL_0234 | ||
| Experiment 13 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
918.90 ng/mL
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Moderate MET expression (MET++) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells | CVCL_2063 | ||
| Experiment 14 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1987.50 ng/mL
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High MET expression (MET+++; IHC 3+) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Lung adenocarcinoma | A-549 cells | CVCL_0023 | ||
| Experiment 15 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10.00 ug/mL | High MET expression (MET+++) | ||
| Method Description |
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 16 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 30.00 ug/mL | Negative MET expression (MET-) | ||
| Method Description |
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).
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| In Vitro Model | Lung adenocarcinoma | HCC827 cells (Afatinib resistant; HA2) | CVCL_2063 | ||
BAT-8003 [Terminated in phase 1]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03884517 | Clinical Status | Phase 1 | ||
| Clinical Description |
An open, escalating phase 1 clinical trial of BAT8003 (for injection) on the safety, tolerability and pharmacokinetics for patients with advanced epithelial cancer.
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References
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