MARDEPODECT

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Synonyms
Status
Molecule Category UNKNOWN
UNII R9Y8EY0G42

Structure

InChI Key AZEXWHKOMMASPA-UHFFFAOYSA-N
Smiles Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ccccc4n3)cc2)n1
InChI
InChI=1S/C25H20N4O/c1-29-16-23(18-12-14-26-15-13-18)25(28-29)20-7-10-22(11-8-20)30-17-21-9-6-19-4-2-3-5-24(19)27-21/h2-16H,17H2,1H3

Physicochemical Descriptors

Property Name Value
Molecular Formula C25H20N4O
Molecular Weight 392.46
AlogP 5.28
Hydrogen Bond Acceptor 5.0
Hydrogen Bond Donor 0.0
Number of Rotational Bond 5.0
Polar Surface Area 52.83
Molecular species NEUTRAL
Aromatic Rings 5.0
Heavy Atoms 30.0
Assay Description Organism Bioactivity Reference
Inhibition of rat recombinant PDE10A transfected in Sf9 cells Rattus norvegicus 0.3715 nM Inhibition of rat recombinant PDE10A transfected in Sf9 cells Rattus norvegicus 0.37 nM
Inhibition of human recombinant PDE10A expressed in baculovirus-SF21 cell system assessed as hydrolysis of [3H]cAMP after 1 hr by liquid scintillation counting Homo sapiens 1.34 nM
Inhibition of PDE10A None 2.6 nM
Inhibition of rat PDE10A Rattus norvegicus 0.18 nM
Inhibition of rat recombinant PDE10A expressed in baculovirus infected insect Sf9 cells using [3H]cAMP as substrate after 60 mins by scintillation counting Rattus norvegicus 0.5012 nM
Displacement of [3H]5-(6,7-dimethoxycinnolin-4-yl)-N-isopropyl-3-methylpyridin-2-amine from PDE10A in Sprague-Dawley rat striatum Rattus norvegicus 0.5 nM Displacement of [3H]5-(6,7-dimethoxycinnolin-4-yl)-N-isopropyl-3-methylpyridin-2-amine from PDE10A in Sprague-Dawley rat striatum Rattus norvegicus 0.17 nM
Inhibition of PDE10A None 0.3 nM
Inhibition of PDE10A (unknown origin) Homo sapiens 2.6 nM
Inhibition of rat recombinant PDE10A expressed in baculovirus infected Sf9 cells using [3H]cAMP as substrate after 60 mins by TopCount scintillation counting analysis Rattus norvegicus 0.6457 nM
Inhibition of full-length human recombinant PDE10A using cyclic AMP as substrate by scintillation proximity assay Homo sapiens 1.26 nM
Inhibition of N-terminal GST-tagged human recombinant PDE10A assessed as substrate hydrolysis using [3H]cAMP as substrate after 30 mins by two-step radiometric assay Homo sapiens 0.37 nM
Binding affinity to PDE10A (unknown origin) Homo sapiens 0.18 nM
Inhibition of PDE10A (unknown origin) Homo sapiens 2.6 nM
HTRF Assay: The PDE enzymatic reaction was carried out in assay buffer (20 mM Tris-HCl pH7.5, 10 mM MgCl2, 0.1% bovine serum albumin) containing enzyme and substrate. The PDE enzymes concentration ranged from 10 pM-250 pM, depending on each enzyme's specific activity. The substrate cyclic nucleotide (cAMP or cGMP) concentration used in the assay was 20 nM for PDE10, and 100 nM for other PDEs. The inhibitory effect of compound was determined by incubating various concentration of inhibitor in the enzymatic assay. Typically, compound was serial diluted in DMSO then further diluted in assay buffer. Next, the compound at varying concentration was mixed with PDE enzyme. The reaction was initiated by addition of cyclic nucleotide substrate, and incubated for 60 minutes at 29° C. The reaction was stopped by addition of lysis buffer from assay kit. The cAMP-d2 and anti-cAMP cryptate in the lysis buffer detected the level of cAMP left from the PDE hydrolysis reaction. Homo sapiens 1.68 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 67.83 %
Inhibition of human PDE10A2 catalytic domain (446 to 789 residues) expressed in Escherichia coli BL21 cells using [3H]-cGMP as substrate after 15 mins by liquid scintillation analysis Homo sapiens 0.37 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 12.08 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 4.782 %
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 17.93 % 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 11.16 % 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 17.93 % 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 11.16 %
Inhibition of recombinant human galectin-3/recombinant human TREM2 interaction assessed as reduction in TR-FRET signal at 10 uM incubated for 3 hrs by TR-FRET assay relative to control Homo sapiens 95.0 %
Inhibition of recombinant human galectin-3/recombinant human TREM2 interaction assessed as reduction in TR-FRET signal incubated for 3 hrs by TR-FRET assay Homo sapiens 91.0 nM
Binding affinity to recombinant human galectin 3 assessed as dissociation constant by fluorescent anisotropy assay Homo sapiens 150.0 nM
Binding affinity to recombinant human galectin 3 assessed as dissociation constant by SPR assay Homo sapiens 290.0 nM
Antiinflammatory activity in mouse BV-2 cells assessed as reduction in Abeta-induced TNFalpha release at 10 uM incubated for 12 hrs by ELISA relative to control Mus musculus 50.0 %
Antiinflammatory activity in mouse BV-2 cells assessed as reduction in Abeta-induced IL-12 release at 10 uM incubated for 12 hrs by ELISA relative to control Mus musculus 40.0 %

Cross References

Resources Reference
ChEMBL CHEMBL562318
DrugBank DB08387
FDA SRS R9Y8EY0G42
Guide to Pharmacology 9617
PDB PF9
PubChem 11581936
SureChEMBL SCHEMBL1414700
ZINC ZINC000035859742
CONTENTS