Linker Information

General Information of This Linker

Linker ID	LIN0MVTCK
Linker Name	PEG2-Val-Cit-PABC
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
Structure	3D MOL		2D MOL
Formula	C22H28N4O6
Isosmiles	C[C@@H](C(=O)NC1=CC=C(C=C1)CO)NC(=O)[C@H](C(C)C)NC(=O)CCN2C(=O)C=CC2=O
PubChem CID	153352098
InChI	InChI=1S/C22H28N4O6/c1-13(2)20(25-17(28)10-11-26-18(29)8-9-19(26)30)22(32)23-14(3)21(31)24-16-6-4-15(12-27)5-7-16/h4-9,13-14,20,27H,10-12H2,1-3H3,(H,23,32)(H,24,31)(H,25,28)/t14-,20-/m0/s1
InChIKey	NSHZSEBCOJNZHE-XOBRGWDASA-N
IUPAC Name	(2S)-2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]-N-[(2S)-1-[4-(hydroxymethyl)anilino]-1-oxopropan-2-yl]-3-methylbutanamide
Pharmaceutical Properties	Molecule Weight	444.5	Polar area	145
	Complexity	740	xlogp Value	-0.1
	Heavy Count	32	Rot Bonds	10
	Hbond acc	6	Hbond Donor	4

Each Antibody-drug Conjugate Related to This Linker

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

DP-303c [Phase 3]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 4 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
*Related Clinical Trial*
NCT Number	NCT05334810	Clinical Status	Phase 2
Clinical Description	A multi-center, open-lable, single-arm phase 2 study to evaluate the efficacy and safety of DP303c in patients with HER2-positive unresectable locally advanced, relapsed, or metastatic breast cancer.
Experiment 2 Reporting the Activity Date of This ADC				[2]
*Related Clinical Trial*
NCT Number	NCT04828616	Clinical Status	Phase 2
Clinical Description	An open-label, multicentre, phase 2 study of DP303c injection in patients with HER2-expressing advanced ovarian cancer.
Experiment 3 Reporting the Activity Date of This ADC				[3]
*Related Clinical Trial*
NCT Number	NCT04826107	Clinical Status	Phase 2
Clinical Description	An open-label, multicentre, phase 2 study of DP303c injection in patients with unresectable locally advanced, recurrent or metastatic gastric cancer with HER2 expression.
Experiment 4 Reporting the Activity Date of This ADC				[4]
*Related Clinical Trial*
NCT Number	NCT04146610	Clinical Status	Phase 1
Clinical Description	A phase 1a, multicenter, open and dose-increasing study of DP303c to evaluate the safety , pharmacokinetics, immunogenicity and antitumor activity of subjects with HER2-positive advanced solid tumors.

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 34 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 7.60% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	DP001 (10 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 16.20% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	T-DM1 (10 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 28.47% (Day 18)	High HER2 expression (HER2+++/++)
Method Description	DP001 (10 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 33.60% (Day 25)	High HER2 expression (HER2+++/++)
Method Description	DP001 (10 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 39.00% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	DP303c (0.3 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45.26% (Day 18)	High HER2 expression (HER2+++/++)
Method Description	DP303c (1 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 54.40% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 0.1 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 82.10% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 1 mg/kg. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 9 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83.94% (Day 18)	High HER2 expression (HER2+++/++)
Method Description	DP303c (3 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 10 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.48% (Day 21)	High HER2 expression (HER2+++/++)
Method Description	DP001 (15 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 11 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 91.60% (Day 25)	High HER2 expression (HER2+++/++)
Method Description	T-DM1 (10 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 12 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.00% (Day 25)	High HER2 expression (HER2+++/++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 13 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.00% (Day 25)	High HER2 expression (HER2+++/++)
Method Description	DP303c (2.5 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 14 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.00% (Day 25)	High HER2 expression (HER2+++/++)
Method Description	DP303c (5 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 15 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.10% (Day 18)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 3 mg/kg. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 16 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.16% (Day 18)	High HER2 expression (HER2+++/++)
Method Description	T-DM1 (10 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 17 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.30% (Day 21)	High HER2 expression (HER2+++/++)
Method Description	T-DM1 (15 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 18 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.00% (Day 21)	High HER2 expression (HER2+++/++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 19 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.00% (Day 21)	High HER2 expression (HER2+++/++)
Method Description	DP303c (15 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 20 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.00% (Day 21)	High HER2 expression (HER2+++/++)
Method Description	DP303c (3 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 21 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.10% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 3 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 22 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.50% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 2.5 mg/kg. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 23 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.50% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 24 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.80% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 5 mg/kg. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 25 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.80% (Day 18)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 26 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.80% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 1 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 27 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.50% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 28 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.54% (Day 18)	High HER2 expression (HER2+++/++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 29 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.80% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 3 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 30 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.10% (Day 25)	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 15 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 31 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.90% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 32 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100.00% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	DP303c (1 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 33 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100.00% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 34 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100.00% (Day 32)	Moderate HER2 expression (HER2++)
Method Description	DP303c (3 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Revealed Based on the Cell Line Data

Click To Hide/Show 14 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 nM	Moderate HER2 expression (HER2++; HER2 MFI=157,231)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 nM	High HER2 expression (HER2+++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.08 nM	High HER2 expression (HER2+++; HER2 MFI=987,353)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.08 nM	Negative HER2 expression (HER2-; HER2 MFI=256)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	High HER2 expression (HER2+++)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	High HER2 expression (HER2+++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.22 nM	Negative HER2 expression (HER2-)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.22 nM	High HER2 expression (HER2+++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 9 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.23 nM	High HER2 expression (HER2+++; HER2 MFI=804,573)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 10 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.23 nM	High HER2 expression (HER2+++; HER2 MFI=892,333)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 11 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.39 nM	High HER2 expression (HER2+++)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 12 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.39 nM	Moderate HER2 expression (HER2++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 13 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 50.00 nM	High HER2 expression (HER2+++; HER2 MFI=1,106,494)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419
Experiment 14 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000.00 nM	High HER2 expression (HER2+++; HER2 MFI=765,629)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419

Anti-FucGM1-46 ADC [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

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

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.24%	Positive FucGM1 expression (FucGM1+++/++)
Method Description	Female CB-17 SCID mice were each inoculated in the flank area with the 5 million tumor cells. To examine the efficacy of anti-FucGM1 ADC-45, mice were dosed with a single IP administration of 0.005 mol/kg.
In Vivo Model	H187 CDX model
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.58%	Positive FucGM1 expression (FucGM1+++/++)
Method Description	Female CB-17 SCID mice were each inoculated in the flank area with the 5 million tumor cells. To examine the efficacy of anti-FucGM1 ADC-45, mice were dosed with a single IP administration of 0.02 mol/kg.
In Vivo Model	H187 CDX model
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501

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					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.20 nM	Positive FucGM1 expression (FucGM1+++/++)
Method Description	Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501

Anti-MSLN-46 ADC [Investigative]

ADC Info

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					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.02 nM	Positive MSLN expression (MSLN+++/++)
Method Description	Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative MSLN expression (MSLN-)
Method Description	Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501

References

Ref 1	A Multi-center, Open-lable, Single-arm Phase II Study to Evaluate the Efficacy and Safety of DP303c in Patients With HER2-positive Unresectable Locally Advanced, Relapsed, or Metastatic Breast Cancer, NCT05334810
Ref 2	An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With HER2-expressing Advanced Ovarian Cancer, NCT04828616
Ref 3	An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With Unresectable Locally Advanced, Recurrent or Metastatic Gastric Cancer With HER2 Expression, NCT04826107
Ref 4	A Phase Ia, Multicenter, Open and Dose-increasing Study of DP303c to Evaluate the Safety , Pharmacokinetics, Immunogenicity and Antitumor Activity of Subjects With HER2-Positive Advanced Solid Tumors, NCT04146610
Ref 5	An Innovative Site-Specific Anti-HER2 Antibody-Drug Conjugate with High Homogeneity and Improved Therapeutic Index. Onco Targets Ther. 2022 Apr 8;15:331-343.
Ref 6	Design, Synthesis, and Structure-Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody-Drug Conjugates. J Med Chem. 2020 Nov 25;63(22):13913-13950. doi: 10.1021/acs.jmedchem.0c01385.

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Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)