Linker Information
General Information of This Linker
| Linker ID |
LIN0TMCCF
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| Linker Name |
DBCO-PEG3-Glu-Val-Cit-PABC
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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 |
C54H72N8O13
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| Isosmiles |
CC(C)C(NC(=O)C(CCC(=O)OC(C)(C)C)NC(=O)COCCOCCOCCNC(=O)CCC(=O)N1Cc2ccccc2C#Cc2ccccc21)C(=O)NC(CCCNC(N)=O)C(=O)Nc1ccc(CO)cc1
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| InChI |
InChI=1S/C54H72N8O13/c1-36(2)49(52(70)60-42(14-10-26-57-53(55)71)50(68)58-41-20-16-37(34-63)17-21-41)61-51(69)43(22-25-48(67)75-54(3,4)5)59-46(65)35-74-32-31-73-30-29-72-28-27-56-45(64)23-24-47(66)62-33-40-13-7-6-11-38(40)18-19-39-12-8-9-15-44(39)62/h6-9,11-13,15-17,20-21,36,42-43,49,63H,10,14,22-35H2,1-5H3,(H,56,64)(H,58,68)(H,59,65)(H,60,70)(H,61,69)(H3,55,57,71)
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| InChIKey |
MFLUIFOUUUKGRE-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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1041.213
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Polar area
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295.15
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Complexity
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75
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xlogp Value
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2.691
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Heavy Count
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75
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Rot Bonds
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30
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Hbond acc
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13
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Hbond Donor
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8
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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
ADC MMAE/F 4+2 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 77.50% (Day 24) | Low HER2 expression (HER2+) | ||
| Method Description |
HCC1954-TDR breast tumor model shows very low HER2 expression with intratumor heterogeneity,representing refractory breast tumors. The HCC1954-TDR cell line was established by continuous treatment with T-DM1 for 8 months. Once tumors reached an average volume of 125mm3,mice were administered with a single dose of the MMAE/F 4+2 ADC (1 mg/kg).
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| In Vivo Model | Breast cancer CDX model | ||||
| In Vitro Model | Breast cancer | Breast cancer cells | Homo sapiens | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 94.10% (Day 24) | Positive HER2 expression (HER2+++/++) | ||
| Method Description |
The in vivo validated model was a xenograft model of human breast tumor consisting of HER2-positive JIMT-1 cells and HER2-negative MDA-MB-231 cells (4:1 ratio) transferred into immunodeficient mice. This admixed tumor grew aggressively and reached a palpable size (100-150 mm 3 ) in most mice 7 days after orthotopic transplantation. Tumor-bearing mice were treated with each ADC at 3 mg/kg.
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| In Vivo Model | Breast cancer CDX model | ||||
| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells/MDA-MB-231 cells | CVCL_2077/CVCL_0062 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.02 nM
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Moderate HER2 expression (HER2++) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast inflammatory carcinoma | KPL-4 cells | CVCL_5310 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.02 nM
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Low HER2 expression (HER2+) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.18 nM
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Moderate HER2 expression (HER2++) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
ADC MMAE/F 2+4 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 87.60% (Day 24) | Positive HER2 expression (HER2+++/++) | ||
| Method Description |
The in vivo validated model was a xenograft model of human breast tumor consisting of HER2-positive JIMT-1 cells and HER2-negative MDA-MB-231 cells (4:1 ratio) transferred into immunodeficient mice. This admixed tumor grew aggressively and reached a palpable size (100-150 mm 3 ) in most mice 7 days after orthotopic transplantation. Tumor-bearing mice were treated with each ADC at 3 mg/kg.
Click to Show/Hide
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| In Vivo Model | Breast cancer CDX model | ||||
| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells/MDA-MB-231 cells | CVCL_2077/CVCL_0062 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.02 nM
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Moderate HER2 expression (HER2++) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast inflammatory carcinoma | KPL-4 cells | CVCL_5310 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.03 nM
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Low HER2 expression (HER2+) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.23 nM
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Moderate HER2 expression (HER2++) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
ADC MMAE/F 2+2 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.03 nM
|
Moderate HER2 expression (HER2++) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast inflammatory carcinoma | KPL-4 cells | CVCL_5310 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.05 nM
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Low HER2 expression (HER2+) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.34 nM
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Moderate HER2 expression (HER2++) | ||
| Method Description |
ADCs were evaluated in vitro cytotoxicity in HER2-positive (KPL-4,JIMT-1,and SKBR-3) and -negative (MDA-MB-231) breast cancer cell lines,human embryonic kidney 293 (HEK293) cells,and human hepatocyte carcinoma (HepG2) cells. All cells were cultured at 37°C under 5% CO2 and passaged before becoming fully confluent up to 20 passages.
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
References
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