Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0DUZAD
ADC Name
ICAM-1-Dxd
Synonyms
ICAM-1-Dxd
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Organization
University of Science and Technology of China; Anhui Provincial Cancer Hospital; People Hospital of Fengyang County; Anhui Medical University; Hefei Comprehensive National Science Center.
Drug Status
Investigative
Structure
Antibody Name
undisclosed
Antigen Name
Intercellular adhesion molecule 1 (ICAM1)
  Antigen Info 
Payload Name
DX-8951 derivative (DXd)
  Payload Info 
Therapeutic Target
DNA topoisomerase 1 (TOP1)
  Target Info 
Linker Name
Mc-Gly-Gly-Phe-Gly
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Deruxtecan
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 6 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Time to Maximum Concentration (Tmax) 0.89±0.36 h
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Maximum Observed Concentration (Cmax) 178.13±15.47 ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Area Under the Concentration-Time Curve (AUC) 12577.62±372.13 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Time to Maximum Concentration (Tmax) 0.65±0.41 h
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Maximum Observed Concentration (Cmax) 208.26±22.39 ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Area Under the Concentration-Time Curve (AUC) 13895.24±402.92 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [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) 12577.62±372.13 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Volume of Distribution (Vd) 77.82±1.54 mL/kg
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Area Under the Concentration-Time Curve (AUC) 13895.24±402.92 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Volume of Distribution (Vd) 51.29±3.17 mL/kg
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Metabolism
Click To Hide/Show 2 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 12577.62±372.13 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Area Under the Concentration-Time Curve (AUC) 13895.24±402.92 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Excretion
Click To Hide/Show 6 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Elimination Half-Life (t1/2) 139.42±3.27 h
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Area Under the Concentration-Time Curve (AUC) 12577.62±372.13 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Clearance (CL) 0.41±0.03 mL/h/kg
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day1-day7).
 [1]
Elimination Half-Life (t1/2) 168.48±2.51 h
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Area Under the Concentration-Time Curve (AUC) 13895.24±402.92 h&#42ug/mL
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
Clearance (CL) 0.33±0.02 mL/h/kg
Pharmacokinetic parameters of conjugated Dxd in mouse serum after iv administration of 5 mg/kg ICAM-1-Dxd, once a week for a total of three doses (day15-day21).
 [1]
General Information of The Activity Data Related to This ADC
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal inhibitory Concentration (lC50) 
0.075
nM
CVCL_0125
Mammary carcinoma
Half Maximal inhibitory Concentration (lC50) 
0.132
nM
CVCL_0062
Breast adenocarcinoma
Half Maximal inhibitory Concentration (lC50) 
0.141
nM
CVCL_1092
Breast ductal carcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) 0.075 nM Positive ICAM-1 expression (ICAM-1+++/++)
Method Description
Cells from triple-negative breast cancer were propagated in slides with 96 chambers, each well containing 5000 cells. The medium was replaced with medium supplemented with nanoparticle Nab PTX, IgG-Dxd, or ICAM-1-Dxd at various concentrations. After 72 h, the toxic effects on the cells were assessed via a CCK-8 test. In brief, the medium containing the pharmaceuticals was discarded, and the cells were carefully rinsed with chilled PBS. The samples were subsequently incubated in a CCK-8 solution maintained at 37 °C for 4 h. The degree to which cell growth was suppressed was determined by comparing the optical density of agent-exposed cells to that of untreated control cells. In addition, extracellular ATP concentrations were quantified via a Beyotime ATP detection kit (S0026).

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In Vitro Model Mammary carcinoma 4T1 cells CVCL_0125
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) 0.132 nM Positive ICAM-1 expression (ICAM-1+++/++)
Method Description
Cells from triple-negative breast cancer were propagated in slides with 96 chambers, each well containing 5000 cells. The medium was replaced with medium supplemented with nanoparticle Nab PTX, IgG-Dxd, or ICAM-1-Dxd at various concentrations. After 72 h, the toxic effects on the cells were assessed via a CCK-8 test. In brief, the medium containing the pharmaceuticals was discarded, and the cells were carefully rinsed with chilled PBS. The samples were subsequently incubated in a CCK-8 solution maintained at 37 °C for 4 h. The degree to which cell growth was suppressed was determined by comparing the optical density of agent-exposed cells to that of untreated control cells. In addition, extracellular ATP concentrations were quantified via a Beyotime ATP detection kit (S0026).

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In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50) 0.141 nM Positive ICAM-1 expression (ICAM-1+++/++)
Method Description
Cells from triple-negative breast cancer were propagated in slides with 96 chambers, each well containing 5000 cells. The medium was replaced with medium supplemented with nanoparticle Nab PTX, IgG-Dxd, or ICAM-1-Dxd at various concentrations. After 72 h, the toxic effects on the cells were assessed via a CCK-8 test. In brief, the medium containing the pharmaceuticals was discarded, and the cells were carefully rinsed with chilled PBS. The samples were subsequently incubated in a CCK-8 solution maintained at 37 °C for 4 h. The degree to which cell growth was suppressed was determined by comparing the optical density of agent-exposed cells to that of untreated control cells. In addition, extracellular ATP concentrations were quantified via a Beyotime ATP detection kit (S0026).

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In Vitro Model Breast ductal carcinoma BT-549 cells CVCL_1092
References
Ref 1 Reprogramming the Tumor Immune Microenvironment with ICAM-1-Targeted Antibody-Drug Conjugates and B7-H3-CD3 Bispecific Antibodies