Payload ID	PAY0BRKLC
Name	seco-CBI-dimer
Synonyms	seco-CBI-dimer    Click to Show/Hide
Target(s)	Human Deoxyribonucleic acid (hDNA)					Target Info
Structure
	3D MOL			2D MOL
Formula	C38H32Cl2N2O11P2
Isosmiles	O=C(/C=C/c1ccc(/C=C/C(=O)N2CC(CCl)c3c2cc(OP(=O)(O)O)c2ccccc32)c(O)c1)N1CC(CCl)c2c1cc(OP(=O)(O)O)c1ccccc21
InChI	InChI=1S/C38H32Cl2N2O11P2/c39-18-24-20-41(30-16-33(52-54(46,47)48)26-5-1-3-7-28(26)37(24)30)35(44)13-10-22-9-11-23(32(43)15-22)12-14-36(45)42-21-25(19-40)38-29-8-4-2-6-27(29)34(17-31(38)42)53-55(49,50)51/h1-17,24-25,43H,18-21H2,(H2,46,47,48)(H2,49,50,51)/b13-10+,14-12+
InChIKey	AUOVWTYPRKEPAY-ADWQEOMMSA-N
Pharmaceutical Properties	Molecule Weight		825.531	Polar area		194.37
	Complexity		55	xlogp Value		7.4064
	Heavy Count		55	Rot Bonds		10
	Hbond acc		7	Hbond Donor		5

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.00% (Day 12)	Positive CD22 expression (CD22+++/++)
Method Description	In vivo efficacy of TDCs aCD22-LC-K149C-10 and aLy6E-LC-K149C-10 in the WSU-DLCL2 xenograft model. single administrations of aCD22-LC-K149C-10 (0.3 mg/kg) to mice bearing CD22-expressing WSU-DLCL2 tumor xenografts model.
In Vivo Model	WSU-DLCL2 CDX model
In Vitro Model	Diffuse large B-cell lymphoma	WSU-DLCL2 cells		CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 87.00 (Day 12)	Positive CD22 expression (CD22+++/++)
Method Description	In vivo efficacy of TDCs aCD22-LC-K149C-10 and aLy6E-LC-K149C-10 in the WSU-DLCL2 xenograft model. single administrations of aCD22-LC-K149C-10 (1 mg/kg) to mice bearing CD22-expressing WSU-DLCL2 tumor xenografts model.
In Vivo Model	WSU-DLCL2 CDX model
In Vitro Model	Diffuse large B-cell lymphoma	WSU-DLCL2 cells		CVCL_1902

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.04 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[2]
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					[2]
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					[2]
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					[2]
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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.01 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.04 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	92.00 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.03 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.14 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					[1]
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 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[1]
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					[1]
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					[1]
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					[1]
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					[1]
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					[1]
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					[1]
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					[1]
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					[1]
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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	52.00 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	81.00 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 130 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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 133 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

Ref 1	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 2	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.