Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0LHCUL
ADC Name
R1c-8988
Synonyms
R1c-8988
   Click to Show/Hide
Organization
BAYER PHARMA AKTIENGESELLSCHAFT
Drug Status
Investigative
Drug-to-Antibody Ratio
3.4
Structure
Antibody Name
TPP-8988
  Antibody Info 
Antigen Name
Interleukin-3 receptor subunit alpha (IL3RA)
  Antigen Info 
Payload Name
KSP Inhbitor
  Payload Info 
Therapeutic Target
Kinesin spindle protein (KSP)
  Target Info 
Linker Name
CN110072556B+ConjugateR1+Linker
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
General Information of The Activity Data Related to This ADC
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal inhibitory Concentration (lC52) 
4.26
nM
CVCL_2119
Adult acute myeloid leukemia
Half Maximal inhibitory Concentration (lC50) 
32.7
nM
CVCL_0064
Childhood acute monocytic leukemia
Full List of Activity Data of This Antibody-drug Conjugate
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.

   Click to Show/Hide
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.

   Click to Show/Hide
In Vitro Model Childhood acute monocytic leukemia MV4-11 cells CVCL_0064
References
Ref 1 Specific antibody-drug conjugates (ADCs) having KSP inhibitors