General Information of This Linker
Linker ID
LIN0OOKTL
Linker Name
CN110072556B+ConjugateR1+Linker
Linker Type
Unclear
Antibody-Linker Relation
Cleavable
Structure
Formula
C9H13N3O6
Isosmiles
O=C(O)NCCNC(CNC(/C=C\C(O)=O)=O)=O
InChI
InChI=1S/C9H13N3O6/c13-6(1-2-8(15)16)12-5-7(14)10-3-4-11-9(17)18/h1-2,11H,3-5H2,(H,10,14)(H,12,13)(H,15,16)(H,17,18)/b2-1-
InChIKey
BVPIZAXUPZVOOZ-UPHRSURJSA-N
Pharmaceutical Properties
Molecule Weight
259.218
Polar area
144.83
Complexity
339.0498112
xlogp Value
-1.8728
Heavy Count
18
Rot Bonds
7
Hbond acc
4
Hbond Donor
5
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
R1c-9476 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC53)
0.304 nM
Positive CD123 expression (CD123+++/++)
Method Description
MOLM-13, 2000cell/well were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Adult acute myeloid leukemia MOLM-13 cells CVCL_2119
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
5.3 nM
Positive CD123 expression (CD123+++/++)
Method Description
MV-4-11, 5000cell/well were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Childhood acute monocytic leukemia MV4-11 cells CVCL_0064
R1c-8988 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC52)
4.26 nM
Positive CD123 expression (CD123+++/++)
Method Description
MOLM-13, 2000cell/well were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Adult acute myeloid leukemia MOLM-13 cells CVCL_2119
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
32.7 nM
Positive CD123 expression (CD123+++/++)
Method Description
MV-4-11, 5000cell/well were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Childhood acute monocytic leukemia MV4-11 cells CVCL_0064
R1c-8987 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC51)
75.7 nM
Positive CD123 expression (CD123+++/++)
Method Description
MOLM-13, 2000cell/well were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Adult acute myeloid leukemia MOLM-13 cells CVCL_2119
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.000000133 M
Positive CD123 expression (CD123+++/++)
Method Description
MV-4-11, 5000cell/well were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Childhood acute monocytic leukemia MV4-11 cells CVCL_0064
R1x-9580 [Investigative]
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 [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.0716 nM
Positive CXCR5 expression (CXCR5+++/++)
Method Description
Cell line Rec-1 were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Mantle cell lymphoma REC-1 cells CVCL_1884
R1x-9024 [Investigative]
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 [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.184 nM
Positive CXCR5 expression (CXCR5+++/++)
Method Description
Cell line Rec-1 were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Mantle cell lymphoma REC-1 cells CVCL_1884
R1x-9574 [Investigative]
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 [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.262 nM
Positive CXCR5 expression (CXCR5+++/++)
Method Description
Cell line Rec-1 were plated at set initial densities in 96-well culture plate with white bottom in the appropriate growth media. 48hours later, the medium was replaced. The ADCs in 10 ul of culture medium inconcentrations from 10-5M to 10-13M were then pipetted to the cells. After 6 hours of incubation at 37°C and 5%carbon dioxide, the medium was changed and the antibody-drug conjugates or metabolites were added by pipette in 10 ul of culture medium in concentrations of 10-5M to 10-13M to the cells (triplicates) in 90 ul. After 96 h, the cell proliferation was detected using the MTT assay (ATCC, Manassas, Virginia, USA, catalogue No. 30-1010K). To this end, the MTT reagent was incubated with the cells for 4 h, followed by lysis of the cells overnight byaddition of the detergent. The dye formed was detected at 570 nm (Infinite M1000 proTecan). The measured data were used to calculate the ICso of the growth inhibition usingthe DRC (dose response curve). The proliferation of cells which were not treated with testsubstance but were otherwise identically treated was defined as the 100% figure.

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In Vitro Model Mantle cell lymphoma REC-1 cells CVCL_1884
References
Ref 1 Specific antibody-drug conjugates (ADCs) having KSP inhibitors