Linker Information

General Information of This Linker

Linker ID	LIN0GWUBC
Linker Name	Gly5-EDA
Linker Type	Sortase-based site-specific conjugation linker
Antibody-Linker Relation	Uncleavable
Structure
Structure	3D MOL		2D MOL
Formula	C12H23N7O5
Isosmiles	NCCNC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)CN
InChI	InChI=1S/C12H23N7O5/c13-1-2-15-9(21)4-17-11(23)6-19-12(24)7-18-10(22)5-16-8(20)3-14/h1-7,13-14H2,(H,15,21)(H,16,20)(H,17,23)(H,18,22)(H,19,24)
InChIKey	APPZOWUYWPMKOP-UHFFFAOYSA-N
Pharmaceutical Properties	Molecule Weight	345.36	Polar area	197.54
	Complexity	24	xlogp Value	-5.5152
	Heavy Count	24	Rot Bonds	11
	Hbond acc	7	Hbond Donor	7

Each Antibody-drug Conjugate Related to This Linker

Full Information of The Activity Data of The ADC(s) Related to This Linker

Tras-Gly5-EDA-Pnu [Investigative]

ADC Info

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% (Day 26)	High HER2 expression (HER2+++; 170,000 HER2 molecules/cell)
Method Description	JIMT-1 cells were transplanted subcutaneously into CB17.SCID mice and tumors were allowed to grow to a volume of 100-150 mm³. Mice were then treated intravenously 3 times weekly with the 1 mg/kg ADC preparations.
In Vivo Model	Trastuzumab-resistant breast cancer CDX model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.70 ng/mL	High HER2 expression (HER2+++; 694,000 HER2 molecules/cell)
Method Description	Briefly, cells were plated on 96-well plates in 75 uL growth medium and grown at 37°C in a humidified incubator in a 7.5% CO₂ atmosphere. After one day incubation, 25 uL of 3.5-fold serial dilutions of each ADC in growth medium were added, typically resulting in final ADC concentrations from 20 ug/mL to 0.02 ng/mL.
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 Inhibitory Concentration (IC50)	14.70 ng/mL	Moderate HER2 expression (HER2++; 32,000 HER2 molecules/cell)
Method Description	Briefly, cells were plated on 96-well plates in 75 uL growth medium and grown at 37°C in a humidified incubator in a 7.5% CO₂ atmosphere. After one day incubation, 25 uL of 3.5-fold serial dilutions of each ADC in growth medium were added, typically resulting in final ADC concentrations from 20 ug/mL to 0.02 ng/mL.
In Vitro Model	Invasive breast carcinoma	T-47D cells		CVCL_0553

Tras-Gly5-EDA-Nemo [Investigative]

ADC Info

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.80 ng/mL	High HER2 expression (HER2+++; 694,000 HER2 molecules/cell)
Method Description	Briefly, cells were plated on 96-well plates in 75 uL growth medium and grown at 37°C in a humidified incubator in a 7.5% CO₂ atmosphere. After one day incubation, 25 uL of 3.5-fold serial dilutions of each ADC in growth medium were added, typically resulting in final ADC concentrations from 20 ug/mL to 0.02 ng/mL.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Tras-Gly5-EDA-Dox [Investigative]

ADC Info

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.80 ng/mL	High HER2 expression (HER2+++; 694,000 HER2 molecules/cell)
Method Description	Briefly, cells were plated on 96-well plates in 75 uL growth medium and grown at 37°C in a humidified incubator in a 7.5% CO₂ atmosphere. After one day incubation, 25 uL of 3.5-fold serial dilutions of each ADC in growth medium were added, typically resulting in final ADC concentrations from 20 ug/mL to 0.02 ng/mL.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

References

Ref 1	Highly Potent, Anthracycline-based Antibody-Drug Conjugates Generated by Enzymatic, Site-specific Conjugation. Mol Cancer Ther. 2017 May;16(5):879-892.