General Information of This Payload
Payload ID
PAY0GCLLM
Name
Ac-Exatecan
Synonyms
Ac-Exatecan
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Target DNA topoisomerase I (TOP1)
Structure
Formula
C26H24FN3O5
Isosmiles
CC[C@@](C(C=C1C(C(CN12)=C3[C@@H](NC(C)=O)CC4)=NC5=C3C4=C(C)C(F)=C5)=C(C2=O)CO6)(O)C6=O
PubChem CID
124411986
InChI
InChI=1S/C26H24FN3O5/c1-4-26(34)16-7-20-23-14(9-30(20)24(32)15(16)10-35-25(26)33)22-18(28-12(3)31)6-5-13-11(2)17(27)8-19(29-23)21(13)22/h7-8,18,34H,4-6,9-10H2,1-3H3,(H,28,31)/t18-,26-/m0/s1
InChIKey
SRCUCWPOTBGIQM-QYBDOPJKSA-N
Pharmaceutical Properties
Molecule Weight
477.492
Polar area
110.52
Complexity
1518.594434
xlogp Value
2.65052
Heavy Count
35
Rot Bonds
2
Hbond acc
7
Hbond Donor
2
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
aU2023279443A1 Example A10 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) > 50% Positive HER2 expression (HER2+++/++)
Method Description
A mixed solvent of PBS and and Matrigel was used to prepare a cell suspension of 5.0x107 cells / mL. The prepared cell suspension was subcutaneously injected to the right flank region of female BALB/c-nu/nu mice at 0.1 mL per mouse. Individuals having a tumor volume within a range of 50 to 500 mm 3 were selected. test compound at a concentration of 3 mg/kg or the solvent alone was intravenously administered. the tumor volume was measured at Day 0 and Day 21.

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In Vivo Model NCI-N87 female BALB/c-nu/nu mice model
wO2024105206A1 3i-5657 [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 [2]
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 Renal cell carcinoma 786-O cells CVCL_1051
Experiment 2 Reporting the Activity Date of This ADC [2]
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 3 Reporting the Activity Date of This ADC [2]
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 [2]
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 [2]
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 9 % carbon dioxide.

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In Vitro Model Renal cell carcinoma 786-O cells (+NE) CVCL_1051
Experiment 6 Reporting the Activity Date of This ADC [2]
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 9 % carbon dioxide.

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In Vitro Model Renal cell carcinoma 786-O cells (-NE) CVCL_1051
wO2024105206A1 3k-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 [2]
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 Renal cell carcinoma 786-O cells CVCL_1051
Experiment 2 Reporting the Activity Date of This ADC [2]
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 [2]
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 [2]
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 [2]
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 10 % carbon dioxide.

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In Vitro Model Renal cell carcinoma 786-O cells (+NE) CVCL_1051
Experiment 6 Reporting the Activity Date of This ADC [2]
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 10 % carbon dioxide.

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In Vitro Model Renal cell carcinoma 786-O cells (-NE) CVCL_1051
References
Ref 1 Antibody-multidrug conjugate
Ref 2 Antibody-drug conjugates cleavable in a tumor microenvironment