Linker ID	LIN0KDOJZ
Linker Name	Mal-PEG2
Linker Type	Flexible reactive (thiol) linker
Antibody-Linker Relation	Uncleavable
Structure
	3D MOL			2D MOL
Formula	C8H11NO4
Isosmiles	C1=CC(=O)N(C1=O)CCOCCO
PubChem CID	19880610
InChI	InChI=1S/C8H11NO4/c10-4-6-13-5-3-9-7(11)1-2-8(9)12/h1-2,10H,3-6H2
InChIKey	IIYLRYHFPWHINS-UHFFFAOYSA-N
IUPAC Name	1-[2-(2-hydroxyethoxy)ethyl]pyrrole-2,5-dione
Pharmaceutical Properties	Molecule Weight		185.18	Polar area		66.8
	Complexity		218	xlogp Value		-0.2
	Heavy Count		13	Rot Bonds		5
	Hbond acc		4	Hbond Donor		1

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.70% (Day 10)	Positive CD22 expression (CD22+++/++)
Method Description	The inhibitory activity of thio-hu anti-CD22-(LC:K149C)-SN36248 against cancer cell growth was compared with a Pinatuzumab vedotin (pina) and polatuzumab vedotin (pola) against various human cancer cell lines in vitro.
In Vitro Model	EBV-related Burkitt lymphoma	Raji cells		CVCL_0511
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.00% (Day 15)	Positive CD22 expression (CD22+++/++)
Method Description	The inhibitory activity of thio-hu anti-CD22-(LC:K149C)-SN36248 against cancer cell growth was compared with a Pinatuzumab vedotin (pina) and polatuzumab vedotin (pola) against various human cancer cell lines in vitro.
In Vitro Model	Diffuse large B-cell lymphoma	WSU-DLCL2 cells		CVCL_1902
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.70% (Day 14)	Positive CD22 expression (CD22+++/++)
Method Description	The inhibitory activity of thio-hu anti-CD22-(LC:K149C)-SN36248 against cancer cell growth was compared with a Pinatuzumab vedotin (pina) and polatuzumab vedotin (pola) against various human cancer cell lines in vitro.
In Vitro Model	Burkitt lymphoma	BJAB.Luc-22R1.2 cells		CVCL_5711
Experiment 4 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.20% (Day 15)	Positive CD22 expression (CD22+++/++)
Method Description	The inhibitory activity of thio-hu anti-CD22-(LC:K149C)-SN36248 against cancer cell growth was compared with a Pinatuzumab vedotin (pina) and polatuzumab vedotin (pola) against various human cancer cell lines in vitro.
In Vitro Model	Burkitt lymphoma	BJAB.Luc cells		CVCL_5711

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.08 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	Diffuse large B-cell lymphoma	WSU-DLCL2 cells		CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.25 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	Burkitt lymphoma	BJAB cells		CVCL_5711
Experiment 3 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	24.00 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.33 nM	High FOLR1 expression(FOLR1+++)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Ovarian endometrioid adenocarcinoma	IGROV-1 cells		CVCL_1304
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	38.00 nM	Moderate FOLR1 expression(FOLR1++)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Lung non-small cell carcinoma	NCI-H2110 cells		CVCL_1530
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Low FOLR1 expression(FOLR1+)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Skin squamous cell carcinoma	A431 cells		CVCL_0037
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative FOLR1 expression(FOLR1-)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Osteosarcoma	SJSA-1 cells		CVCL_1697

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	9.00 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	Diffuse large B-cell lymphoma	WSU-DLCL2 cells		CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	15.00 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065
Experiment 3 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	61.00 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	Burkitt lymphoma	BJAB cells		CVCL_5711

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	9.60 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	Diffuse large B-cell lymphoma	WSU-DLCL2 cells		CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	17.00 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	T acute lymphoblastic leukemia	Jurkat cells		CVCL_0065
Experiment 3 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	51.00 nM	Positive CD22 expression (CD22+++/++)
Method Description	Seco-CBI-Dimer TDCs Exhibit Potent Antigen-Dependent Antiproliferation Effects in Vitro. All cell-based assay results are reported as the arithmetic mean of at least three separate runs (n = 3).
In Vitro Model	Burkitt lymphoma	BJAB cells		CVCL_5711

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	43.00 nM	Negative MSLN expression(MSLN-)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Ovarian endometrioid adenocarcinoma	IGROV-1 cells		CVCL_1304
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	50.00 nM	Moderate MSLN expression(MSLN++)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Lung non-small cell carcinoma	NCI-H2110 cells		CVCL_1530
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative MSLN expression(MSLN-)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Skin squamous cell carcinoma	A431 cells		CVCL_0037
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative MSLN expression(MSLN-)
Method Description	Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model	Osteosarcoma	SJSA-1 cells		CVCL_1697

Ref 1	An Anti-CD22-seco-CBI-Dimer Antibody-Drug Conjugate (ADC) for the Treatment of Non-Hodgkin Lymphoma That Provides a Longer Duration of Response than Auristatin-Based ADCs in Preclinical Models. Mol Cancer Ther. 2021 Feb;20(2):340-346.
Ref 2	Antibody-Drug Conjugates Derived from Cytotoxic seco-CBI-Dimer Payloads Are Highly Efficacious in Xenograft Models and Form Protein Adducts In Vivo. Bioconjug Chem. 2019 May 15;30(5):1356-1370. doi: 10.1021/acs.bioconjchem.9b00133. Epub 2019 Apr 22.
Ref 3	MORAb-202, an Antibody-Drug Conjugate Utilizing Humanized Anti-human FR Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity. Mol Cancer Ther. 2018 Dec;17(12):2665-2675. doi: 10.1158/1535-7163.MCT-17-1215. Epub 2018 Sep 27.