Payload Information

General Information of This Payload
Payload ID
PAY0IXEJQ
Name
AGD-0182
Synonyms
AGD-0182; CHEMBL5205301; SCHEMBL17302870; HY-144585; CS-0432631
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Target(s) Microtubule (MT)
 Target Info 
Structure
Formula
C38H63N9O7
Isosmiles
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N)OC)OC)N(C)C(=O)[C@H]([C@H](C)N=[N+]=[N-])NC(=O)[C@H](C(C)C)NC
PubChem CID
118548818
InChI
InChI=1S/C38H63N9O7/c1-11-23(4)33(46(8)38(52)32(25(6)44-45-40)43-37(51)31(41-7)22(2)3)29(53-9)21-30(48)47-19-15-18-28(47)34(54-10)24(5)36(50)42-27(35(39)49)20-26-16-13-12-14-17-26/h12-14,16-17,22-25,27-29,31-34,41H,11,15,18-21H2,1-10H3,(H2,39,49)(H,42,50)(H,43,51)/t23-,24+,25-,27-,28-,29+,31-,32-,33-,34+/m0/s1
InChIKey
TYROHBPOIIUEQF-HFQNRHNCSA-N
IUPAC Name
(2S)-N-[(2S,3S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-azido-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamide
Pharmaceutical Properties
Molecule Weight
758
Polar area
187
Complexity
1290
xlogp Value
3.7
Heavy Count
54
Rot Bonds
22
Hbond acc
10
Hbond Donor
4
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Half Maximal Inhibitory Concentration (IC50) 0.6 nM
Karpas-299 cells/Karpas BVR cells
ALK-positive anaplastic large cell lymphoma
CVCL_1324 
[1]
Half Maximal Inhibitory Concentration (IC50) 1.8 nM
MCF7-F (fulvestrant resistant) cells
Invasive breast carcinoma
CVCL_0031 
[2]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
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 [3]
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 [3]
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.

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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 3 Reporting the Activity Date of This ADC [3]
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.

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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 4 Reporting the Activity Date of This ADC [3]
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.

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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
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 [4]
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 Discovery and Development of Dolastatin 10-Derived Antibody Drug Conjugate Anticancer Drugs. J Nat Prod. 2022 Mar 25;85(3):666-687. doi: 10.1021/acs.jnatprod.1c01135. Epub 2022 Jan 24.
Ref 2 Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg Med Chem. 2007 Sep 1;15(17):5837-44. doi: 10.1016/j.bmc.2007.05.070. Epub 2007 Jun 6.
Ref 3 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 4 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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