BEGACESTAT

/static/temp/default.svg Search structure
Synonyms
Status
Molecule Category UNKNOWN
UNII 3666C56BBU
EPA CompTox DTXSID00227710

Structure

InChI Key PSXOKXJMVRSARX-SCSAIBSYSA-N
Smiles O=S(=O)(N[C@H](CO)C(C(F)(F)F)C(F)(F)F)c1ccc(Cl)s1
InChI
InChI=1S/C9H8ClF6NO3S2/c10-5-1-2-6(21-5)22(19,20)17-4(3-18)7(8(11,12)13)9(14,15)16/h1-2,4,7,17-18H,3H2/t4-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C9H8ClF6NO3S2
Molecular Weight 391.74
AlogP 2.78
Hydrogen Bond Acceptor 4.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 5.0
Polar Surface Area 66.4
Molecular species NEUTRAL
Aromatic Rings 1.0
Heavy Atoms 22.0

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
- 2-414 - - -
Enzyme
- 2-414 - - -
Ion channel Other ion channel Miscellaneous ion channel Presenilin ER Ca2+ leak channel family
- 2-414 - - -
Assay Description Organism Bioactivity Reference
Inhibition of gamma-secretase expressed in CHO cells expressing human recombinant APP assessed as amyloid beta40 aggregation None 15.0 nM
Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production None 15.0 nM
Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells Homo sapiens 15.0 nM
Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in transgenic 2576 mouse brain at 5 mg/kg, po after 4 hrs Mus musculus 37.0 %
Inhibition of gamma secretase-mediated amyloid beta (1 to 42) production in transgenic 2576 mouse brain at 5 mg/kg, po after 4 hrs Mus musculus 25.0 %
Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay Homo sapiens 8.0 nM
Inhibition of gamma secretase-mediated total amyloid beta production in healthy human plasma at 600 mg/kg, po administered as single dose Homo sapiens 40.0 %
Inhibition of gamma secretase-mediated total amyloid beta production in transgenic 2576 mouse plasma at 10 mg/kg Mus musculus 9.0 %
Inhibition of gamma secretase-mediated total amyloid beta production in transgenic 2576 mouse brain at 10 mg/kg Mus musculus 22.0 %
Inhibition of gamma secretase-mediated total amyloid beta production in plasma of patient with Alzheimer's disease at 450 mg/kg Homo sapiens 28.0 %
Inhibition of gamma secretase-mediated total amyloid beta production in human plasma at 450 mg/kg measured at 2 hrs post-dose Homo sapiens 28.0 %
Inhibition of gamma-secretase (unknown origin) expressed in N2a NL/N cells coexpressing betaAPPNL and NotchdeltaE assessed as Abeta42 secretion by ELISA Homo sapiens 414.0 nM
Inhibition of gamma-secretase (unknown origin) expressed in N2a NL/N cells coexpressing betaAPPNL and NotchdeltaE assessed as Abeta40 secretion by ELISA Homo sapiens 203.0 nM
Inhibition of partially purified human gamma-secretase-mediated cleavage of notch fusion protein measured after overnight incubation by ELISA Homo sapiens 11.0 nM
Inhibition of partially purified human gamma-secretase-mediated cleavage of MBP-APPc125Sw fusion protein measured after overnight incubation by ELISA Homo sapiens 1.6 nM
Inhibition of gamma-secretase in CHO cells after overnight incubation by luciferase reporter gene assay Cricetulus griseus 353.0 nM
Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA Homo sapiens 1.6 nM
Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA Homo sapiens 10.5 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 -0.36 %
Inhibition of gamma secretase (unknown origin) mediated APP cleavage in CHO cells expressing APP Swedish KM/NL mutant assessed as reduction in amyloid beta 40 after 24 hrs by sandwich ELISA Homo sapiens 14.8 nM
Inhibition of gamma secretase (unknown origin) mediated Notch M1726V mutant activation in CHO K1 cells after 48 hrs by chemiluminescence assay Homo sapiens 208.5 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 20.95 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 8.764 %
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 0.17 % 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 0.19 % 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 0.19 % 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 0.17 %

Related Entries

Cross References

Resources Reference
ChEMBL CHEMBL463981
DrugBank DB12263
FDA SRS 3666C56BBU
Guide to Pharmacology 6979
PubChem 11269353
SureChEMBL SCHEMBL3314371
ZINC ZINC000030691750
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