Linker ID	LIN0OXUQL
Linker Name	Mc-Val-Ala-PABC
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
	3D MOL			2D MOL
Formula	C25H34N4O6
Isosmiles	C[C@@H](C(=O)NC1=CC=C(C=C1)CO)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN2C(=O)C=CC2=O
PubChem CID	100029273
InChI	InChI=1S/C25H34N4O6/c1-16(2)23(28-20(31)7-5-4-6-14-29-21(32)12-13-22(29)33)25(35)26-17(3)24(34)27-19-10-8-18(15-30)9-11-19/h8-13,16-17,23,30H,4-7,14-15H2,1-3H3,(H,26,35)(H,27,34)(H,28,31)/t17-,23-/m0/s1
InChIKey	DAMSURYLURICHN-SBUREZEXSA-N
IUPAC Name	6-(2,5-dioxopyrrol-1-yl)-N-[(2S)-1-[[(2S)-1-[4-(hydroxymethyl)anilino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]hexanamide
Pharmaceutical Properties	Molecule Weight		486.6	Polar area		145
	Complexity		786	xlogp Value		0.9
	Heavy Count		35	Rot Bonds		13
	Hbond acc		6	Hbond Donor		4

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Partial Response (PR)	1.72%
Patients Enrolled	Female patients (age 18 years) with EOC if they had evidence of progressive disease during or within 6 months of receiving a platinum regimen.
Administration Dosage	1 of 6 dose levels (0.025-0.40 mg/kg) every 3 weeks (Q3W), utilizing a standard 3+3 design (dose-limiting toxicity [DLT] period: 21 days).
Related Clinical Trial
NCT Number	NCT02539719	Clinical Status	Phase 1
Clinical Description	A phase 1a/1b dose escalation and expansion study of SC-003 as a single-agent and in combination with ABBV-181 in subjects with platinum-resistant/ refractory ovarian cancer.
Primary Endpoint	The MTD for the Q3W schedule was 0.30 mg/kg and the SC-003 doses selected for the dose-expansion phase of the study were 0.30 mg/kg and 0.20 mg/kg.
Other Endpoint	ORR=5.17% (N=3/58), 3 patients achieved PR. All responses were observed at 0.20-0.30mg/kg. Responses were not durable, with only 1 PR confirmed on the follow-up 16-week scan.

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 42.79%	High EGFR expression (EGFR+++)
Method Description	The inhibitory activity of Cetuximab-(FGX16-11) against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg.
In Vivo Model	Colon cancer CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 63.01%	High EGFR expression (EGFR+++)
Method Description	The inhibitory activity of Cetuximab-(FGX16-11) against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 5 mg/kg.
In Vivo Model	Colon cancer CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724
Experiment 3 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.22%	High EGFR expression (EGFR+++)
Method Description	The inhibitory activity of Cetuximab-(FGX16-11) against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 10 mg/kg.
In Vivo Model	Colon cancer CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724
Experiment 4 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.98%	High EGFR expression (EGFR+++)
Method Description	The inhibitory activity of Cetuximab-(FGX16-11) against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 20 mg/kg.
In Vivo Model	Colon cancer CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724
Experiment 5 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High EGFR expression (EGFR+++)
Method Description	The inhibitory activity of Cetuximab-(FGX16-11) against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 40 mg/kg.
In Vivo Model	Colon cancer CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8 pM	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	10 pM	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	71 pM	Moderate HER2 expression (HER2++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	14 pM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	71 pM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	17 pM	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	18 pM	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.11 nM	Moderate HER2 expression (HER2++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	22 pM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.11 nM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	25 pM	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	54 pM	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.28 nM	Moderate HER2 expression (HER2++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	31 pM	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	32 pM	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.21 nM	Moderate HER2 expression (HER2++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	32 pM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.19 nM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	43 pM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.16 nM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	46 pM	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	59 pM	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.13 nM	Moderate HER2 expression (HER2++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.27 nM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.36 nM	Positive PSMA expression (PSMA +++/++)
Method Description	The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	14.5 nM	High HER2 expression (HER2+++)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Invasive breast carcinoma	BT474 HerDR cells		CVCL_0179
Experiment 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	157.6 nM	High HER2 expression (HER2+++)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000 nM	Negative HER2 expression (HER2-)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000 nM	Negative HER2 expression (HER2-)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	265.3 nM	High PD-L1 expression (PD-L1+++)
Method Description	The in vitro cytotoxicity of ADC 1 and ADC 2 was evaluated in three PD-L1-positive cell lines, i.e., Calu-1, MDA-MB-231, and SK-MES, and one PD-L1-negative cell line, i.e., AsPC-1.
In Vitro Model	Lung squamous cell carcinoma	SK-MES-1 cells		CVCL_0630
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 663.08 nM	Negative PD-L1 expression (PD-L1-)
Method Description	The in vitro cytotoxicity of ADC 1 and ADC 2 was evaluated in three PD-L1-positive cell lines, i.e., Calu-1, MDA-MB-231, and SK-MES, and one PD-L1-negative cell line, i.e., AsPC-1.
In Vitro Model	Pancreatic ductal adenocarcinoma	AsPC-1 cells		CVCL_0152
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 663.08 nM	High PD-L1 expression (PD-L1+++)
Method Description	The in vitro cytotoxicity of ADC 1 and ADC 2 was evaluated in three PD-L1-positive cell lines, i.e., Calu-1, MDA-MB-231, and SK-MES, and one PD-L1-negative cell line, i.e., AsPC-1.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 663.08 nM	High PD-L1 expression (PD-L1+++)
Method Description	The in vitro cytotoxicity of ADC 1 and ADC 2 was evaluated in three PD-L1-positive cell lines, i.e., Calu-1, MDA-MB-231, and SK-MES, and one PD-L1-negative cell line, i.e., AsPC-1.
In Vitro Model	Lung squamous cell carcinoma	Calu-1 cells		CVCL_0608

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	9.75 nM	High PD-L1 expression (PD-L1+++)
Method Description	The in vitro cytotoxicity of ADC 3 was quickly evaluated in three PD-L1-positive cell lines, ie, MDA-MB-231, PC 9, and A431, and one PD-L1-negative cell line, ie, Romas.
In Vitro Model	Lung adenocarcinoma	PC-9 cells		CVCL_B260
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	10.33 nM	High PD-L1 expression (PD-L1+++)
Method Description	The in vitro cytotoxicity of ADC 3 was quickly evaluated in three PD-L1-positive cell lines, ie, MDA-MB-231, PC 9, and A431, and one PD-L1-negative cell line, ie, Romas.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	11.94 nM	High PD-L1 expression (PD-L1+++)
Method Description	The in vitro cytotoxicity of ADC 3 was quickly evaluated in three PD-L1-positive cell lines, ie, MDA-MB-231, PC 9, and A431, and one PD-L1-negative cell line, ie, Romas.
In Vitro Model	Skin squamous cell carcinoma	A431 cells		CVCL_0037

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	6.613 pM	High CD33 expression (CD33+++)
Method Description	Cytotoxicity of ADC to MV4-11 cells
In Vitro Model	Childhood acute monocytic leukemia	MV4-11 cells		CVCL_0064

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	6.699 pM	High CD33 expression (CD33+++)
Method Description	Cytotoxicity of ADC to MV4-11 cells
In Vitro Model	Childhood acute monocytic leukemia	MV4-11 cells		CVCL_0064

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	12.3 pM	High CD33 expression (CD33+++)
Method Description	Cytotoxicity of ADC to MV4-11 cells
In Vitro Model	Childhood acute monocytic leukemia	MV4-11 cells		CVCL_0064

Experiment 1 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.01116 nM	High HER2 expression (HER2+++)
Method Description	Cytotoxicity of ADC to SK-BR-3 cells
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Experiment 1 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.02107 nM	High HER2 expression (HER2+++)
Method Description	Cytotoxicity of ADC to SK-BR-3 cells
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Experiment 1 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.0231 nM	Positive HER2 expression (HER2+++/++)
Method Description	HCC 1954, 1000cell/well was added to the designated 384-well cell culture plate in the appropriate growth media. The ADCs stock solution was diluted in series in a ratio of 1:3 to produce 10 diluted solutions with different concentrations (the compound stock solution was an L-His buffer salt solution with a concentration of about 2 mg/mL, which was diluted with PBS, and the initial maximum concentration at test point was about 500 mg/mL). 4ul of the compound diluted solutions with different concentrations was distributed into a 384-well plate. After 96 hours, the plate was taken from the incubator and equilibrated at room temperature for 10 minutes. 40uL of CellTiter-Glo reagent was added to each well to be tested (the ratio of CellTiter-Glo reagent to medium was 1:1).the plate was then placed at room temperature for 30 minutes, and then reading was carried out on an EnSpire reader for cell counting.    Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 2 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.0563 nM	Positive HER2 expression (HER2+++/++)
Method Description	NCI-N87, 1000cell/well was added to the designated 384-well cell culture plate in the appropriate growth media. The ADCs stock solution was diluted in series in a ratio of 1:3 to produce 10 diluted solutions with different concentrations (the compound stock solution was an L-His buffer salt solution with a concentration of about 2 mg/mL, which was diluted with PBS, and the initial maximum concentration at test point was about 500 mg/mL). 4ul of the compound diluted solutions with different concentrations was distributed into a 384-well plate. After 96 hours, the plate was taken from the incubator and equilibrated at room temperature for 10 minutes. 40uL of CellTiter-Glo reagent was added to each well to be tested (the ratio of CellTiter-Glo reagent to medium was 1:1).the plate was then placed at room temperature for 30 minutes, and then reading was carried out on an EnSpire reader for cell counting.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.0783 nM	Positive HER2 expression (HER2+++/++)
Method Description	BT-474, 1000cell/well was added to the designated 384-well cell culture plate in the appropriate growth media. The ADCs stock solution was diluted in series in a ratio of 1:3 to produce 10 diluted solutions with different concentrations (the compound stock solution was an L-His buffer salt solution with a concentration of about 2 mg/mL, which was diluted with PBS, and the initial maximum concentration at test point was about 500 mg/mL). 4ul of the compound diluted solutions with different concentrations was distributed into a 384-well plate. After 96 hours, the plate was taken from the incubator and equilibrated at room temperature for 10 minutes. 40uL of CellTiter-Glo reagent was added to each well to be tested (the ratio of CellTiter-Glo reagent to medium was 1:1).the plate was then placed at room temperature for 30 minutes, and then reading was carried out on an EnSpire reader for cell counting.    Click to Show/Hide
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 4 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.1518 nM	Positive HER2 expression (HER2+++/++)
Method Description	SK-OV-3, 1000cell/well was added to the designated 384-well cell culture plate in the appropriate growth media. The ADCs stock solution was diluted in series in a ratio of 1:3 to produce 10 diluted solutions with different concentrations (the compound stock solution was an L-His buffer salt solution with a concentration of about 2 mg/mL, which was diluted with PBS, and the initial maximum concentration at test point was about 500 mg/mL). 4ul of the compound diluted solutions with different concentrations was distributed into a 384-well plate. After 96 hours, the plate was taken from the incubator and equilibrated at room temperature for 10 minutes. 40uL of CellTiter-Glo reagent was added to each well to be tested (the ratio of CellTiter-Glo reagent to medium was 1:1).the plate was then placed at room temperature for 30 minutes, and then reading was carried out on an EnSpire reader for cell counting.    Click to Show/Hide
In Vitro Model	Ovarian serous adenocarcinoma	SKOV-3 cells		CVCL_0532
Experiment 5 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	> 1.6495 nM	Negative HER2 expression (HER2-)
Method Description	MCF-7, 1000cell/well was added to the designated 384-well cell culture plate in the appropriate growth media. The ADCs stock solution was diluted in series in a ratio of 1:3 to produce 10 diluted solutions with different concentrations (the compound stock solution was an L-His buffer salt solution with a concentration of about 2 mg/mL, which was diluted with PBS, and the initial maximum concentration at test point was about 500 mg/mL). 4ul of the compound diluted solutions with different concentrations was distributed into a 384-well plate. After 96 hours, the plate was taken from the incubator and equilibrated at room temperature for 10 minutes. 40uL of CellTiter-Glo reagent was added to each well to be tested (the ratio of CellTiter-Glo reagent to medium was 1:1).the plate was then placed at room temperature for 30 minutes, and then reading was carried out on an EnSpire reader for cell counting.    Click to Show/Hide
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 6 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	> 1.6495 nM	Negative HER2 expression (HER2-)
Method Description	MDA-MB-468, 1000cell/well was added to the designated 384-well cell culture plate in the appropriate growth media. The ADCs stock solution was diluted in series in a ratio of 1:3 to produce 10 diluted solutions with different concentrations (the compound stock solution was an L-His buffer salt solution with a concentration of about 2 mg/mL, which was diluted with PBS, and the initial maximum concentration at test point was about 500 mg/mL). 4ul of the compound diluted solutions with different concentrations was distributed into a 384-well plate. After 96 hours, the plate was taken from the incubator and equilibrated at room temperature for 10 minutes. 40uL of CellTiter-Glo reagent was added to each well to be tested (the ratio of CellTiter-Glo reagent to medium was 1:1).the plate was then placed at room temperature for 30 minutes, and then reading was carried out on an EnSpire reader for cell counting.    Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419

Experiment 1 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.04488 nM	High DLL3 expression (DLL3+++)
Method Description	Cytotoxicity of ADC to NCI-H82 cells
In Vitro Model	Lung small cell carcinoma	NCI-H82 cells		CVCL_1591

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	36.5 nM
Method Description	SW620 (ATCC) cells were selected as the cell line for in vitro activity detection experiments. 2000 cells were inoculated into each well of a 96-well cell culture plate and cultured for 20-24 hours. The antibody-drug conjugate prepared according to the method in Example 3 was formulated with L15 cell culture medium containing 10% FBS into 11 concentration gradients of test solution: 1000, 166.7, 55.6, 18.6, 6.17, 2.06, 0.69, 0.23, 0.08, 0.008 and OnM. 100 ul of the diluted test solution per well was added to the culture plate containing the inoculated cells and incubated in a 37°C, 5% CO, incubator for 144 hours. Then, CellTiter-Glo® Luminescent Cell Viability Assay Reagent (50 ul/well) was added, and the mixture was shaken at 500 rpm at room temperature for 10 minutes. The data were read using a SpectraMaxL microplate reader (OD570nm, with 2-second interval readings), and the IC52 results were calculated.    Click to Show/Hide
In Vitro Model	Colon adenocarcinoma	SW620 cells		CVCL_0547
Experiment 2 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	37.5 nM
Method Description	22Rv1 (ATCC) cells were selected as the cell line for in vitro activity detection experiments. 2000 cells were inoculated into each well of a 96-well cell culture plate and cultured for 20-24 hours. The antibody-drug conjugate prepared according to the method in Example 3 was formulated with L15 cell culture medium containing 10% FBS into 11 concentration gradients of test solution: 1000, 166.7, 55.6, 18.6, 6.17, 2.06, 0.69, 0.23, 0.08, 0.008 and OnM. 100 ul of the diluted test solution per well was added to the culture plate containing the inoculated cells and incubated in a 37°C, 5% CO, incubator for 144 hours. Then, CellTiter-Glo® Luminescent Cell Viability Assay Reagent (50 ul/well) was added, and the mixture was shaken at 500 rpm at room temperature for 10 minutes. The data were read using a SpectraMaxL microplate reader (OD570nm, with 2-second interval readings), and the IC50 results were calculated.    Click to Show/Hide
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045
Experiment 3 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	38.4 nM
Method Description	NCI-H820 (ATCC) cells were selected as the cell line for in vitro activity detection experiments. 2000 cells were inoculated into each well of a 96-well cell culture plate and cultured for 20-24 hours. The antibody-drug conjugate prepared according to the method in Example 3 was formulated with L15 cell culture medium containing 10% FBS into 11 concentration gradients of test solution: 1000, 166.7, 55.6, 18.6, 6.17, 2.06, 0.69, 0.23, 0.08, 0.008 and OnM. 100 ul of the diluted test solution per well was added to the culture plate containing the inoculated cells and incubated in a 37°C, 5% CO, incubator for 144 hours. Then, CellTiter-Glo® Luminescent Cell Viability Assay Reagent (50 ul/well) was added, and the mixture was shaken at 500 rpm at room temperature for 10 minutes. The data were read using a SpectraMaxL microplate reader (OD570nm, with 2-second interval readings), and the IC50 results were calculated.    Click to Show/Hide
In Vitro Model	Lung papillary adenocarcinoma	NCI-H820 cells		CVCL_1592
Experiment 4 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	50.23 nM
Method Description	OVCAR-8 (ATCC) cells were selected as the cell line for in vitro activity detection experiments. 2000 cells were inoculated into each well of a 96-well cell culture plate and cultured for 20-24 hours. The antibody-drug conjugate prepared according to the method in Example 3 was formulated with L15 cell culture medium containing 10% FBS into 11 concentration gradients of test solution: 1000, 166.7, 55.6, 18.6, 6.17, 2.06, 0.69, 0.23, 0.08, 0.008 and OnM. 100 ul of the diluted test solution per well was added to the culture plate containing the inoculated cells and incubated in a 37°C, 5% CO, incubator for 144 hours. Then, CellTiter-Glo® Luminescent Cell Viability Assay Reagent (50 ul/well) was added, and the mixture was shaken at 500 rpm at room temperature for 10 minutes. The data were read using a SpectraMaxL microplate reader (OD570nm, with 2-second interval readings), and the IC64 results were calculated.    Click to Show/Hide
In Vitro Model	High grade ovarian serous adenocarcinoma	OVCAR-8 cells		CVCL_1629
Experiment 5 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	62.38 nM
Method Description	HCC827 (ATCC) cells were selected as the cell line for in vitro activity detection experiments. 2000 cells were inoculated into each well of a 96-well cell culture plate and cultured for 20-24 hours. The antibody-drug conjugate prepared according to the method in Example 3 was formulated with L15 cell culture medium containing 10% FBS into 11 concentration gradients of test solution: 1000, 166.7, 55.6, 18.6, 6.17, 2.06, 0.69, 0.23, 0.08, 0.008 and OnM. 100 ul of the diluted test solution per well was added to the culture plate containing the inoculated cells and incubated in a 37°C, 5% CO, incubator for 144 hours. Then, CellTiter-Glo® Luminescent Cell Viability Assay Reagent (50 ul/well) was added, and the mixture was shaken at 500 rpm at room temperature for 10 minutes. The data were read using a SpectraMaxL microplate reader (OD570nm, with 2-second interval readings), and the IC64 results were calculated.    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells		CVCL_2063
Experiment 6 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	85.6 nM
Method Description	LNCaP (ATCC) cells were selected as the cell line for in vitro activity detection experiments. 2000 cells were inoculated into each well of a 96-well cell culture plate and cultured for 20-24 hours. The antibody-drug conjugate prepared according to the method in Example 3 was formulated with L15 cell culture medium containing 10% FBS into 11 concentration gradients of test solution: 1000, 166.7, 55.6, 18.6, 6.17, 2.06, 0.69, 0.23, 0.08, 0.008 and OnM. 100 ul of the diluted test solution per well was added to the culture plate containing the inoculated cells and incubated in a 37°C, 5% CO, incubator for 144 hours. Then, CellTiter-Glo® Luminescent Cell Viability Assay Reagent (50 ul/well) was added, and the mixture was shaken at 500 rpm at room temperature for 10 minutes. The data were read using a SpectraMaxL microplate reader (OD570nm, with 2-second interval readings), and the IC50 results were calculated.    Click to Show/Hide
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395

Experiment 1 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal Effective Concentration (EC50)	2.63 nM	High hCCR2 expression (hCCR2+++)
Method Description	THP 1, 15,000cells/254uL per welld were plated at set in 384 well flat plate, in the appropriate growth media. The cell plates were dosed with 5uL of the hCCR2 targeting-ADC samples and then incubated at 37°C for 20 hours. At the end of the incubation 10uL/well of the QUANTJ-LucTM (InvivoGenftrep-qlc1) were added and luminescence was measured immediately using the LeadSeeker.    Click to Show/Hide
In Vitro Model	Acute monoblastic/monocytic leukemia, Childhood acute monocytic leukemia	THP1 cells		CVCL_0006

Ref 1	Tamrintamab pamozirine (SC-003) in patients with platinum-resistant/refractory ovarian cancer: Findings of a phase 1 study. Gynecol Oncol. 2020 Sep;158(3):640-645.
Ref 2	DNA sequence-selective G-A cross-linking ADC payloads for use in solid tumour therapies. Commun Biol. 2022 Jul 29;5(1):741.
Ref 3	Amatoxin antibody-drug conjugates and uses thereof; 2020-10-29.
Ref 4	Synthesis and evaluation of highly releasable and structurally stable antibody-SN-38-conjugates. Drug Deliv. 2021 Dec;28(1):2603-2617.
Ref 5	Development of bifunctional anti-PD-L1 antibody MMAE conjugate with cytotoxicity and immunostimulation. Bioorg Chem. 2021 Nov;116:105366.
Ref 6	Antibody-drug conjugate
Ref 7	Domide molecular glue derivative and use thereof
Ref 8	Linker, antibody-drug conjugate including same, and uses thereof
Ref 9	Antibody-drug conjugates, intermediates, preparation methods and uses
Ref 10	Antibody-drug conjugates