General Information of This Linker
Linker ID
LIN0FRRUD
Linker Name
18i-5657 Linker
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C31H55N9O10
Isosmiles
CN(CCN(C)CCN(CCNC(CNC(CCC(O)=O)=O)=O)C)CC(N[C@@H](CC(N)=O)C(N1CCC[C@H]1C(N[C@@H](C(C)C)C(O)=O)=O)=O)=O
InChI
InChI=1S/C31H55N9O10/c1-20(2)28(31(49)50)36-29(47)22-7-6-11-40(22)30(48)21(17-23(32)41)35-26(44)19-39(5)16-15-38(4)14-13-37(3)12-10-33-25(43)18-34-24(42)8-9-27(45)46/h20-22,28H,6-19H2,1-5H3,(H2,32,41)(H,33,43)(H,34,42)(H,35,44)(H,36,47)(H,45,46)(H,49,50)/t21-,22-,28-/m0/s1
InChIKey
SDCHKDPAZIEINN-VPYPWEPUSA-N
Pharmaceutical Properties
Molecule Weight
713.834
Polar area
264.12
Complexity
1134.533557
xlogp Value
-3.5444
Heavy Count
50
Rot Bonds
24
Hbond acc
11
Hbond Donor
7
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
WO2024105206A1 18i-5657 2 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 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 25 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Renal cell carcinoma 786-O cells (+NE) CVCL_1051
Experiment 2 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, 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 14 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Plasma cell myeloma, Multiple myeloma NCI-H929 cells (+NE) CVCL_1600
Experiment 3 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 14 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Breast inflammatory carcinoma SUM149PT cells (-NE) CVCL_3422
Experiment 4 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 14 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Breast inflammatory carcinoma SUM149PT cells (+NE) CVCL_3422
Experiment 5 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 25 % 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)
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 28 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Colon adenocarcinoma HT29 cells (+NE) CVCL_0320
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) (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 14 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Plasma cell myeloma, Multiple myeloma NCI-H929 cells (-NE) CVCL_1600
Experiment 8 Reporting the Activity Date of This ADC [1]
Efficacy Data Activity Concentration at -50% (AC50) > 1000 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 8 % carbon dioxide.

   Click to Show/Hide
In Vitro Model Colon adenocarcinoma HT29 cells (-NE) CVCL_0320
References
Ref 1 Antibody-drug conjugates cleavable in a tumor microenvironment