General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0SJHKQ
ADC Name
wO2024105206A1 12i-5657
Synonyms
WO2024105206A1 12i-5657
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Organization
VINCERX PHARMA GMBH
Drug Status
Investigative
Drug-to-Antibody Ratio
5
Structure
Antibody Name
TPP-5657
 Antibody Info 
Antigen Name
Undisclosed
Payload Name
CHH0189, 12i-5657, Payload
 Payload Info 
Linker Name
CHH0189, 12i-5657, Linker
 Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Intermediate Q42
General Information of The Activity Data Related to This ADC
Revealed Based on the Cell Line Data
Click To Hide/Show 10 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Activity Concentration at -50% (AC50) 
1.0- 9.9
nM
CVCL_2119
Acute monoblastic/monocytic leukemia, Adult acute monocytic leukemia, Myelodysplastic syndrome
Activity Concentration at -50% (AC50) 
1.0- 9.9
nM
CVCL_2119
Acute monoblastic/monocytic leukemia, Adult acute monocytic leukemia, Myelodysplastic syndrome
Activity Concentration at -50% (AC50) 
1.0- 9.9
nM
CVCL_0320
Colon adenocarcinoma
Activity Concentration at -50% (AC50) 
1.0- 9.9
nM
CVCL_1600
Plasma cell myeloma, Multiple myeloma
Activity Concentration at -50% (AC50) 
1.0- 9.9
nM
CVCL_3422
Breast inflammatory carcinoma
Activity Concentration at -50% (AC50) 
10- 99
nM
CVCL_1051
Renal cell carcinoma
Activity Concentration at -50% (AC50) 
100- 999
nM
CVCL_1051
Renal cell carcinoma
Activity Concentration at -50% (AC50) 
100- 999
nM
CVCL_0320
Colon adenocarcinoma
Activity Concentration at -50% (AC50) 
100- 999
nM
CVCL_1600
Plasma cell myeloma, Multiple myeloma
Activity Concentration at -50% (AC50) 
100- 999
nM
CVCL_3422
Breast inflammatory carcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Revealed Based on the Cell Line Data
Click To Hide/Show 10 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
1.0- 9.9 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (MOLM13: 3000 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone and was added followed by a 96 h incubation in an incubator at 37°C and 5 % carbon dioxide.

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In Vitro Model Acute monoblastic/monocytic leukemia, Adult acute monocytic leukemia, Myelodysplastic syndrome MOLM13 cells (-NE) CVCL_2119
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
1.0- 9.9 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (MOLM13: 3000 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone, whereas to the second set the test compound and 5nM hum.neutrophil elastase were added followed by a 96 h incubation in an incubator at 37°C and 5 % carbon dioxide.

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In Vitro Model Acute monoblastic/monocytic leukemia, Adult acute monocytic leukemia, Myelodysplastic syndrome MOLM13 cells (+NE) CVCL_2119
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
1.0- 9.9 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (HT29: 1200 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone and was added followed by a 96 h incubation in an incubator at 37°C and 25 % carbon dioxide.

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In Vitro Model Colon adenocarcinoma HT29 cells (+NE) CVCL_0320
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
1.0- 9.9 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (NCI H292: 2500 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone, whereas to the second set the test compound and 5nM hum.neutrophil elastase were added followed by a 96 h incubation in an incubator at 37°C and 11 % carbon dioxide.

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In Vitro Model Plasma cell myeloma, Multiple myeloma NCI-H929 cells (+NE) CVCL_1600
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
1.0- 9.9 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (SUM149PT 2000 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone, whereas to the second set the test compound and 5nM hum.neutrophil elastase were added followed by a 96 h incubation in an incubator at 37°C and 11 % carbon dioxide.

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In Vitro Model Breast inflammatory carcinoma SUM149PT cells (+NE) CVCL_3422
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
10- 99 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (786-0: 1500 cells/ well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone, whereas to the second set the test compound and 5nM hum.neutrophil elastase were added followed by a 96 h incubation in an incubator at 37°C and 22 % carbon dioxide.

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In Vitro Model Renal cell carcinoma 786-O cells (+NE) CVCL_1051
Experiment 7 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
100- 999 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (786-0: 1500 cells/ well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone and was added followed by a 96 h incubation in an incubator at 37°C and 22 % carbon dioxide.

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In Vitro Model Renal cell carcinoma 786-O cells (-NE) CVCL_1051
Experiment 8 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
100- 999 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (HT29: 1200 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone and was added followed by a 96 h incubation in an incubator at 37°C and 5 % carbon dioxide.

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In Vitro Model Colon adenocarcinoma HT29 cells (-NE) CVCL_0320
Experiment 9 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
100- 999 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (NCI H292: 2500 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone and was added followed by a 96 h incubation in an incubator at 37°C and 11 % carbon dioxide.

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In Vitro Model Plasma cell myeloma, Multiple myeloma NCI-H929 cells (-NE) CVCL_1600
Experiment 10 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50)
100- 999 nM
Method Description
After cell counting a defined cell number was sowed into a 96-well culture plate with white bottom (from Costar #3610) (SUM149PT 2000 cells/well) in total volume 100 uL. The cells (except MOLM-13 cells, these cells were directly treated) were then incubated in an incubator at 37°C and 5 % carbon dioxide. After 48 h, the medium was replaced. The treatment started by adding the test compounds in 10 uL of culture medium to the cells in triplicates. Concentrations ranging from 10-5 M to 10-13 M were chosen. Two identical treated sets of samples were prepared. One set was treated with the test compound alone, whereas to the second set the test compound and 5nM hum.neutrophil elastase were added followed by a 96 h incubation in an incubator at 37°C and 11 % carbon dioxide.

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In Vitro Model Breast inflammatory carcinoma SUM149PT cells (-NE) CVCL_3422
References
Ref 1 Antibody-drug conjugates cleavable in a tumor microenvironment