Linker Information

General Information of This Linker
Linker ID
LIN0AUOJQ
Linker Name
AGS-62P1 linker
Linker Type
P-acetyl phenylalanine-based site-specific conjugation linker
Antibody-Linker Relation
Uncleavable
Structure
Formula
C11H13NO3
Isosmiles
C/C(=N\OCC(=O)O)c1ccc(C)cc1
InChI
InChI=1S/C11H13NO3/c1-8-3-5-10(6-4-8)9(2)12-15-7-11(13)14/h3-6H,7H2,1-2H3,(H,13,14)/b12-9+
InChIKey
RCSVLSZANULHIO-FMIVXFBMSA-N
Pharmaceutical Properties
Molecule Weight
207.229
Polar area
58.89
Complexity
15
xlogp Value
1.82022
Heavy Count
15
Rot Bonds
4
Hbond acc
3
Hbond Donor
1
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
AGS-62P1 [Terminated in phase 1]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
27.00%
Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

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In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
35.10%
Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

   Click to Show/Hide
In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
38.00%
Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

   Click to Show/Hide
In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
84.00%
Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

   Click to Show/Hide
In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20-12.00 nM
Positive FLT3 Expression (FLT3+++/++)
Method Description
The cytotoxic activity of AGS-62P1 was evaluated against a panel of AmL cell lines in vitro.
In Vitro Model Acute myeloid leukemia Acute myeloid leukemia cells Homo sapiens
References
Ref 1 Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model. Oncotarget. 2022 Dec 20;13:1359-1368.
Ref 2 AGS62P1, a novel site-specific antibody drug conjugate targeting FLT3 exhibits potent anti-tumor activity regardless of FLT3 kinase activation status.

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