Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0HLHGE
ADC Name	HER2-acetal-ADC 12
Synonyms	HER2-acetal-ADC-12 Click to Show/Hide
Drug Status	Investigative
Indication	In total 1 Indication(s) Breast cancer [ICD11:2C60-2C65] Investigative
Drug-to-Antibody Ratio	1.3
	3D MOL	2D MOL
Antibody Name	Trastuzumab		Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (ERBB2)		Antigen Info
Payload Name	Monomethyl auristatin F		Payload Info
Therapeutic Target	Microtubule (MT)		Target Info
Linker Name	Clravable-TAMRA-acetal based linker 12		Linker Info
Conjugate Type	Conjugates were generated by copper catalyzed cycloaddition (CuAAC) with non-natural amino acid containing an azide moiety.

General Information of The Activity Data Related to This ADC

Discovered Using Cell Line-derived Xenograft Model

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

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 100	%	SK-BR-3 cells	Breast adenocarcinoma

Revealed Based on the Cell Line Data

Click To Hide/Show 2 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	0.22	nM	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 100	nM	MDA-MB-231 cells	Breast adenocarcinoma

Full List of Activity Data of This Antibody-drug Conjugate

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 30)	Positive HER2 expression (HER2 +++/++)
Method Description	NOD-SCID mice with heterotopic SKBR-3 tumor xenografts were injected intravenously with either ADC 12 (1.12 mg/kg; group A), PBS 1x (vehicle; group B) or Kadcyla (1.12 mg/kg; group C) and tumor volume was measured every 2-3 days for 30 days.
In Vivo Model	SKBR-3 CDX model
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

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)	0.22 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Cells were incubated with increasing concentrations in tested compounds for 96 h and cell viability was determined by MTS assay.
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)	> 100 nM	Negative HER2 expression (HER2-)
Method Description	Cells were incubated with increasing concentrations in tested compounds for 96 h and cell viability was determined by MTS assay.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062

References

Ref 1	A Novel Family of Acid-Cleavable Linker Based on Cyclic Acetal Motifs for the Production of Antibody-Drug Conjugates with High Potency and Selectivity. Bioconjug Chem. 2022 Oct 19;33(10):1860-1866. doi: 10.1021/acs.bioconjchem.2c00314. Epub 2022 Sep 15.