Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0BOUZK
ADC Name
CD117-ADC
Synonyms
CD117-ADC
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Organization
National Institutes of Health; The University of Tokyo; Leidos Biomedical Research, Inc.; Frederick National Laboratory for Cancer Research; Magenta Therapeutics.
Drug Status
Investigative
Structure
Antibody Name
undisclosed
Antigen Name
Mast/stem cell growth factor receptor Kit (KIT)
  Antigen Info 
Payload Name
SG3199
  Payload Info 
Therapeutic Target
Human Deoxyribonucleic acid (hDNA)
  Target Info 
Linker Name
Mal-PEG8-Val-Ala-PABC
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Tesirine
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 8 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 5038 ng/mL
0.2 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 77347 h&#42ng/mL
0.2 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Maximum Observed Concentration (Cmax) 7440 ng/mL
0.3 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 121960 h&#42ng/mL
0.3 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Maximum Observed Concentration (Cmax) 8176 ng/mL
0.4 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 190659 h&#42ng/mL
0.4 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Maximum Observed Concentration (Cmax) 15620 ng/mL
0.6 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 381895 h&#42ng/mL
0.6 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Distribution
Click To Hide/Show 4 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 77347 h&#42ng/mL
0.2 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 121960 h&#42ng/mL
0.3 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 190659 h&#42ng/mL
0.4 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 381895 h&#42ng/mL
0.6 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Metabolism
Click To Hide/Show 4 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 77347 h&#42ng/mL
0.2 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 121960 h&#42ng/mL
0.3 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 190659 h&#42ng/mL
0.4 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 381895 h&#42ng/mL
0.6 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Excretion
Click To Hide/Show 6 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Elimination Half-Life (t1/2) 11.3 h
To evaluate the drug clearance rate, the plasma concentration of ADC in circulation was measured after a single intravenous injection of CD117-ADC (0.4 mg/kg) in rhesus monkeys (n = 1)
 [1]
Elimination Half-Life (t1/2) 31.92 h
To evaluate the drug clearance rate, the plasma concentration of ADC in circulation was measured after a single intravenous injection of CD117-ADC (0.6 mg/kg) in rhesus monkeys (n = 1)
 [1]
Area Under the Concentration-Time Curve (AUC) 77347 h&#42ng/mL
0.2 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 121960 h&#42ng/mL
0.3 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 190659 h&#42ng/mL
0.4 Mg/kg CD117-ADC in rhesus macaques.
 [1]
Area Under the Concentration-Time Curve (AUC) 381895 h&#42ng/mL
0.6 Mg/kg CD117-ADC in rhesus macaques.
 [1]
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 Effective Concentration (EC50) 
0.0265
nM
Undisclosed
Normal
Half Maximal Effective Concentration (EC50) 
0.0521
nM
Undisclosed Undisclosed
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 Effective Concentration (EC50) 0.0265 nM Positive CD34 expression ( CD34+++/++)
Method Description
Primary human CD34+ cells were purchased from STEMCELL technologies (Vancouver, BC, Canada). The cells were obtained using Institutional Review Board (IRB)-approved consent forms and protocols. The steady-state human bone marrow CD34+ cells (3 donors, STEMCELL technologies) or purified mobilized CD34+ cells from two healthy rhesus macaques were cultured (2500 cells/well in 384-well plate) in serum-free StemSpan SFEM media (45 ul, STEMCELL Technologies) supplemented with 100 ng/ml each of Interleukin 6 (IL-6), fms-related tyrosine kinase 3 ligand (FLT3L), and thrombopoietin (TPO). Escalating doses of CD117-ADC as well as IgG isotype control-conjugated ADC were added (5 ul ADC added to 45 ul cells). After 6 days of culture, the number of viable CD34 + CD90+ cells were evaluated by flow cytometry using 7-Aminoactinomycin D (7-AAD as a viability marker, Biolegend, San Diego, CA, USA), CD34 BV785 (clone 561, BioLegend), and CD90 APC (Clone 5E10, BioLegend) detection antibodies. Cells were acquired on a BD Celesta Instrument and analyzed with FloJo. The EC50 and EC90 values were calculated with GraphPad Prism software.

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In Vitro Model Normal Rhesus CD34+ cells Macaca mulatta
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50) 0.0521 nM Positive CD34 expression ( CD34+++/++)
Method Description
Primary human CD34+ cells were purchased from STEMCELL technologies (Vancouver, BC, Canada). The cells were obtained using Institutional Review Board (IRB)-approved consent forms and protocols. The steady-state human bone marrow CD34+ cells (3 donors, STEMCELL technologies) or purified mobilized CD34+ cells from two healthy rhesus macaques were cultured (2500 cells/well in 384-well plate) in serum-free StemSpan SFEM media (45 ul, STEMCELL Technologies) supplemented with 100 ng/ml each of Interleukin 6 (IL-6), fms-related tyrosine kinase 3 ligand (FLT3L), and thrombopoietin (TPO). Escalating doses of CD117-ADC as well as IgG isotype control-conjugated ADC were added (5 ul ADC added to 45 ul cells). After 6 days of culture, the number of viable CD34 + CD90+ cells were evaluated by flow cytometry using 7-Aminoactinomycin D (7-AAD as a viability marker, Biolegend, San Diego, CA, USA), CD34 BV785 (clone 561, BioLegend), and CD90 APC (Clone 5E10, BioLegend) detection antibodies. Cells were acquired on a BD Celesta Instrument and analyzed with FloJo. The EC50 and EC90 values were calculated with GraphPad Prism software.

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In Vitro Model . Human CD34+ cells Homo sapiens
References
Ref 1 Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model