AVAGACESTAT

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Synonyms
Status
Molecule Category UNKNOWN
UNII TQ44WWY45Q
EPA CompTox DTXSID40150811

Structure

InChI Key XEAOPVUAMONVLA-QGZVFWFLSA-N
Smiles NC(=O)[C@@H](CCC(F)(F)F)N(Cc1ccc(-c2ncon2)cc1F)S(=O)(=O)c1ccc(Cl)cc1
InChI
InChI=1S/C20H17ClF4N4O4S/c21-14-3-5-15(6-4-14)34(31,32)29(17(18(26)30)7-8-20(23,24)25)10-13-2-1-12(9-16(13)22)19-27-11-33-28-19/h1-6,9,11,17H,7-8,10H2,(H2,26,30)/t17-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C20H17ClF4N4O4S
Molecular Weight 520.89
AlogP 3.92
Hydrogen Bond Acceptor 6.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 9.0
Polar Surface Area 119.39
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 34.0

Bioactivity

Mechanism of Action Action Reference
Gamma-secretase inhibitor INHIBITOR PubMed
Protein: Gamma-secretase
Description: Presenilin-1
Organism : Homo sapiens
P49768 ENSG00000080815
Protein: Gamma-secretase
Description: Presenilin-2
Organism : Homo sapiens
P49810 ENSG00000143801
Protein: Gamma-secretase
Description: Gamma-secretase subunit APH-1B
Organism : Homo sapiens
Q8WW43 ENSG00000138613
Protein: Gamma-secretase
Description: Nicastrin
Organism : Homo sapiens
Q92542 ENSG00000162736
Protein: Gamma-secretase
Description: Gamma-secretase subunit APH-1A
Organism : Homo sapiens
Q96BI3 ENSG00000117362
Protein: Gamma-secretase
Description: Gamma-secretase subunit PEN-2
Organism : Homo sapiens
Q9NZ42 ENSG00000205155
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Protease Aspartic protease Aspartic protease AD clan Aspartic protease A22A subfamily Aspartic protease A22A regulatory subfamily
- 0-2 - - -
Enzyme
- 0-2 - - -
Ion channel Other ion channel Miscellaneous ion channel Presenilin ER Ca2+ leak channel family
- 0-2 - - -
Assay Description Organism Bioactivity Reference
Inhibition of human gamma secretase-mediated amyloid beta (1 to 40) production expressed in human H4 cells Homo sapiens 0.3 nM
Inhibition of gamma secretase-mediated total amyloid beta production in healthy human plasma at 200 mg/kg administered as single dose Homo sapiens 50.0 %
Inhibition of gamma secretase-mediated total amyloid beta production in healthy human CSF at 200 mg/kg administered as single dose Homo sapiens 40.0 %
Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cells expressing human APP swedish mutant Homo sapiens 0.225 nM
Inhibition of gamma-secretase None 0.3 nM
SANGER: Inhibition of human NCI-H810 cell growth in a cell viability assay. Homo sapiens 425.98 nM
SANGER: Inhibition of human 786-0 cell growth in a cell viability assay. Homo sapiens 321.73 nM
Inhibition of partially purified human gamma-secretase-mediated cleavage of notch fusion protein measured after overnight incubation by ELISA Homo sapiens 1.5 nM
Inhibition of partially purified human gamma-secretase-mediated cleavage of MBP-APPc125Sw fusion protein measured after overnight incubation by ELISA Homo sapiens 0.13 nM
Inhibition of gamma-secretase in CHO cells after overnight incubation by luciferase reporter gene assay Cricetulus griseus 71.0 nM
Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA Homo sapiens 0.13 nM
Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA Homo sapiens 1.5 nM
Inhibition of gamma-secretase in human H4-8Sw cells assessed as reduction in amyloid beta (1 to 42) formation Homo sapiens 0.27 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -7.76 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 10.63 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 7.238 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.29 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.04 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.04 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.29 %

Cross References

Resources Reference
ChEMBL CHEMBL1090771
DrugBank DB11893
FDA SRS TQ44WWY45Q
Guide to Pharmacology 6489
PDB EN9
PubChem 46883536
SureChEMBL SCHEMBL310019
ZINC ZINC000043202993
CONTENTS