General Information of This Linker
Linker ID
LIN0ZCMSI
Linker Name
2i-5657 Linker
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C29H43N5O11
Isosmiles
CC(C)[C@H](NC([C@@H]1CCCN1C([C@@H](NC(CCOCCNC(CCCCCN2C(C=CC2=O)=O)=O)=O)CC(O)=O)=O)=O)C(O)=O
InChI
InChI=1S/C29H43N5O11/c1-18(2)26(29(43)44)32-27(41)20-7-6-14-33(20)28(42)19(17-25(39)40)31-22(36)11-15-45-16-12-30-21(35)8-4-3-5-13-34-23(37)9-10-24(34)38/h9-10,18-20,26H,3-8,11-17H2,1-2H3,(H,30,35)(H,31,36)(H,32,41)(H,39,40)(H,43,44)/t19-,20-,26-/m0/s1
InChIKey
VGLQBDGTGWQWOT-DYLHXGEVSA-N
Pharmaceutical Properties
Molecule Weight
637.687
Polar area
228.82
Complexity
1080.859965
xlogp Value
-0.8294
Heavy Count
45
Rot Bonds
20
Hbond acc
9
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
wO2024105206A1 2i-5657 [Investigative]
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 Half Maximal inhibitory Concentration (lC50)
13&#459.9 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
103&#4599 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1003&#45999 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1003&#45999 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
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) (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 7 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Renal cell carcinoma 786-O cells (+NE) CVCL_1051
Experiment 6 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 6 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Plasma cell myeloma, Multiple myeloma NCI-H929 cells (+NE) CVCL_1600
Experiment 7 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 6 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Breast inflammatory carcinoma SUM149PT cells (+NE) CVCL_3422
Experiment 8 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 and was added followed by a 96 h incubation in an incubator at 37°C and 7 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Renal cell carcinoma 786-O cells (-NE) CVCL_1051
Experiment 9 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) (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 6 % carbon dioxide.

   Click to Show/Hide
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)
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) (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 6 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Breast inflammatory carcinoma SUM149PT cells (-NE) CVCL_3422
wO2024105206A1 2k-2658 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
103&#4599 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
103&#4599 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
103&#4599 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1003&#45999 nM
Method Description
The cells were cultivated according to the standard method using the growth media suggest by provider The test was carried out by detaching the cells with a solution of Accutase in PBS buffer (fromBiochrom AG #L2143).
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Experiment 5 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 and was added followed by a 96 h incubation in an incubator at 37°C and 8 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Renal cell carcinoma 786-O cells (-NE) CVCL_1051
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 8 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Renal cell carcinoma 786-O cells (+NE) CVCL_1051
References
Ref 1 Antibody-drug conjugates cleavable in a tumor microenvironment