General Information of This Linker
Linker ID
LIN0ATYUQ
Linker Name
Mal-EBE-Mal
Linker Type
Thiol-sensitive linker
Antibody-Linker Relation
Uncleavable
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Glypican 3 ADC [Phase 1 (Terminated)]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00%
Positive GPC3 expression (GPC3+++/++)
Method Description
Female NOD/SCID mice were inoculated subcutaneously in the right flank with 500,000 Hep3B cells. Three weekly administration of A2-tub at 0.12 mol/kg.
In Vivo Model Hep3B CDX model
In Vitro Model Childhood hepatocellular carcinoma Hep 3B2.1-7 cells CVCL_0326
MUC16-55 ADC [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 50) Positive MUC16 expression (MUC16 +++/++)
Method Description
In vivo efficacy of MUC16 targeting ADCs in the Ovcar3 tumor model. MUC16-55 ADC dosed at 5 mg/kg (in each study with the exact dosing for control) IV in SCID mice.
In Vivo Model OVCR-3 CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.80 nM
Positive MUC16 expression (MUC16 +++/++)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative MUC16 expression (MUC16-)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Normal HEK293 cells CVCL_0045
MUC16-56 ADC [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.83 nM
Positive MUC16 expression (MUC16 +++/++)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative MUC16 expression (MUC16-)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Normal HEK293 cells CVCL_0045
3A5-56 ADC [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.18 nM
Positive MUC16 expression (MUC16 +++/++)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative MUC16 expression (MUC16-)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Normal HEK293 cells CVCL_0045
3A5-55 ADC [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.40 nM
Positive MUC16 expression (MUC16 +++/++)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative MUC16 expression (MUC16-)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Normal HEK293 cells CVCL_0045
References
Ref 1 Adnectin-drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors. Protein Eng Des Sel. 2018 May 1;31(5):159-171. doi: 10.1093/protein/gzy013.
Ref 2 Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids. Bioorg Med Chem. 2020 Dec 1;28(23):115785. doi: 10.1016/j.bmc.2020.115785. Epub 2020 Oct 11.