lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)CCCOc1nc(Oc2ccc3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: BEYCUVURKUGSEQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 386.6
Compound (SMILES): COCC(COc1nc(Oc2ccc3c(c2)COB3O)c(Cl)cc1C#N)OC
InChIKey: WLRPIEXEHDHNIW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 404.62
Compound (SMILES): N#Cc1cc(Cl)c(Oc2ccc3c(c2)COB3O)nc1OCCOC1CC1
InChIKey: JXQLQPODTZFKHM-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 386.6
Compound (SMILES): CC(C)OCCOc1nc(Oc2ccc3c(c2)COB3O)cc(C(F)(F)F)c1C#N
InChIKey: DSHINXNFGWBHRA-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 422.17
Compound (SMILES): CC(=O)CCCOc1nc(Oc2ccc3c(c2)COB3O)cc(C(F)(F)F)c1C#N
InChIKey: NSVZCMUAFBWPEB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 420.15
Compound (SMILES): CC(C)OCCOc1nc(Oc2ccc3c(c2)COB3O)c(C#N)cc1C#N
InChIKey: VUKLRTNDLAMXGZ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 379.18
Compound (SMILES): Cc1cc(Oc2nc(OCCOC(C)C)c(C#N)cc2Cl)cc2c1B(O)OC2
InChIKey: XQZSDSGBZZUHKR-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 402.64
Compound (SMILES): CC(=O)CCCOc1nc(Oc2cc(C)c3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: KRPGYDWKKKFLRX-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 400.63
Compound (SMILES): CC(C)OCCOc1nc(Oc2cc(F)c3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: UPBKTTZHNZAEQA-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 406.61
Compound (SMILES): CC(=O)CCCOc1nc(Oc2cc(F)c3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: XONFIBGUKUGPPG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 404.59
Compound (SMILES): CC(=O)CCCOc1nc(Oc2ccc3c(c2)COB3O)c(C#N)cc1Cl
InChIKey: CGGDBFMTDWNCOY-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 386.6
Compound (SMILES): CS(=O)(=O)n1cc2c(n1)CN([C@H]1CNC(c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: YMSSYXMVVRUURO-AIMZMQLPSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 μM; kcat=75 s−1; kcat/Km=1.5×106 M−1s−1. A typical reaction contains approximately 50 μM enzyme, 50 μM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 μL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 μM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL).
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 397.45, ALogP 0.72, HBA 7, HBD 2, PSA 93.25, QED 0.79
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cn(S(=O)(=O)C4CC4)nc3C2)CNC1c1cc(F)c(F)cc1F
InChIKey: BGOQVBLKHZYDSL-HCUPATASSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 μM; kcat=75 s−1; kcat/Km=1.5×106 M−1s−1. A typical reaction contains approximately 50 μM enzyme, 50 μM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 μL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 μM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL).
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 441.48, ALogP 1.39, HBA 7, HBD 2, PSA 93.25, QED 0.7
Compound (SMILES): CS(=O)(=O)n1cc2c(n1)CN([C@@H]1C[C@H](N)C(c3cc(F)ccc3F)N(CC(N)=O)C1)C2
InChIKey: WWFYXAIFVBQLLZ-MSJIKYQXSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 μM; kcat=75 s−1; kcat/Km=1.5×106 M−1s−1. A typical reaction contains approximately 50 μM enzyme, 50 μM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 μL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 μM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL).
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 454.5, ALogP -0.09, HBA 8, HBD 2, PSA 127.55, QED 0.65
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cn[nH]c3C2)CN(CC(=O)N2CC[C@@H](F)C2)C1c1cc(F)ccc1F
InChIKey: FHVSRZATIGXZJU-ZZHBOUHGSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 μM; kcat=75 s−1; kcat/Km=1.5×106 M−1s−1. A typical reaction contains approximately 50 μM enzyme, 50 μM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 μL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 μM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 448.49, ALogP 1.72, HBA 5, HBD 2, PSA 81.49, QED 0.74
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@H]2CC[C@@H](CO)C2)cc1)c1nc2ccccc2[nH]1
InChIKey: PBAYSSFAKIJKMQ-AEFFLSMTSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.212 nM (pChEMBL 9.670000076293945)
Descriptors: MW 413.48, ALogP 4.86, HBA 5, HBD 2, PSA 88.1, QED 0.44
Compound (SMILES): COc1cccc2[nH]c(Nc3ccc(Oc4ncccc4C4CCOCC4)cc3)nc12
InChIKey: UUGNPCRGOSHPOJ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.418 nM (pChEMBL 9.380000114440918)
Descriptors: MW 416.48, ALogP 5.4, HBA 6, HBD 2, PSA 81.29, QED 0.44
Compound (SMILES): CC(=O)N1CCC[C@@H](c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)C1
InChIKey: WWFTWZCLJUHLBP-LJQANCHMSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 1.61 nM (pChEMBL 8.789999961853027)
Descriptors: MW 440.5, ALogP 4.71, HBA 5, HBD 1, PSA 88.18, QED 0.45
Compound (SMILES): CC(=O)N1CC=C(c2cncnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CC1
InChIKey: XYMVYSRDJNUGHV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 1.56 nM (pChEMBL 8.8100004196167)
Descriptors: MW 439.48, ALogP 4.01, HBA 6, HBD 1, PSA 101.07, QED 0.47
Compound (SMILES): COc1cncc(-c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)c1
InChIKey: VZFUGMMBNIQUMI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 4.08 nM (pChEMBL 8.390000343322754)
Descriptors: MW 426.5, ALogP 6.3, HBA 7, HBD 1, PSA 69.16, QED 0.34
Compound (SMILES): O=C1CC[C@@H](c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)C1
InChIKey: CMAUYGZSACSSCR-MRXNPFEDSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.021 nM (pChEMBL 10.680000305175781)
Descriptors: MW 397.43, ALogP 4.82, HBA 5, HBD 1, PSA 84.94, QED 0.49
Compound (SMILES): COc1ccc(-c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)nc1
InChIKey: ANBUNECBLHRAMJ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 8.77 nM (pChEMBL 8.0600004196167)
Descriptors: MW 422.44, ALogP 5.05, HBA 6, HBD 1, PSA 89.99, QED 0.39
Compound (SMILES): O=C1CC[C@@H](c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CCN1
InChIKey: WODVTQSQPXFTLX-MRXNPFEDSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.0595 nM (pChEMBL 10.229999542236328)
Descriptors: MW 426.48, ALogP 4.36, HBA 5, HBD 2, PSA 96.97, QED 0.46
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@@H]2CCCOCC2)cc1)c1nc2ccccc2[nH]1
InChIKey: WLPIWSXIHUAMEG-QGZVFWFLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.0505 nM (pChEMBL 10.300000190734863)
Descriptors: MW 413.48, ALogP 5.27, HBA 5, HBD 1, PSA 77.1, QED 0.45
Compound (SMILES): O=C(c1ccc(Oc2ncccc2-c2ccnc(Cl)c2)cc1)c1nc2ccccc2[nH]1
InChIKey: NSJBQEQJJVJAQH-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 1.63 nM (pChEMBL 8.789999961853027)
Descriptors: MW 426.86, ALogP 5.7, HBA 5, HBD 1, PSA 80.76, QED 0.29
Compound (SMILES): O=C(c1ccc(Oc2ncccc2-c2ccnc(F)c2)cc1)c1nc2ccccc2[nH]1
InChIKey: INRMQSCSZLMLCA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 410.41, ALogP 5.18, HBA 5, HBD 1, PSA 80.76, QED 0.32
Compound (SMILES): C[C@]1(O)CC[C@@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: NKMTUVVLEAOPMD-GYCJOSAFSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 2.86 nM (pChEMBL 8.539999961853027)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): C[C@@]1(O)CC[C@@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: NKMTUVVLEAOPMD-VOIUYBSRSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 10.7 nM (pChEMBL 7.96999979019165)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): C[C@]1(O)CC[C@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: NKMTUVVLEAOPMD-FYSMJZIKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 2.31 nM (pChEMBL 8.640000343322754)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): C[C@@]1(O)CC[C@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: NKMTUVVLEAOPMD-UPCLLVRISA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.897 nM (pChEMBL 9.050000190734863)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): O[C@H]1CCC[C@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: HHGBPGARRHXTDJ-WMZOPIPTSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.737 nM (pChEMBL 9.130000114440918)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): O=C1CCCC(c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CC1
InChIKey: PTUZHKGYWLATFH-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.077 nM (pChEMBL 10.109999656677246)
Descriptors: MW 425.49, ALogP 5.6, HBA 5, HBD 1, PSA 84.94, QED 0.33
Compound (SMILES): Fc1ccc(Cn2c(Nc3ccc(Oc4ncccc4C4CCOCC4)cc3)nc3ccccc32)cc1
InChIKey: FSOPRIQXAJDGAA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 9.12 nM (pChEMBL 8.039999961853027)
Descriptors: MW 494.57, ALogP 7.05, HBA 6, HBD 1, PSA 61.2, QED 0.26
Compound (SMILES): CN1CCC(c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CCC1=O
InChIKey: RJPPEFFGEGMKFF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.218 nM (pChEMBL 9.65999984741211)
Descriptors: MW 440.5, ALogP 4.71, HBA 5, HBD 1, PSA 88.18, QED 0.45
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@@H]2CCC[C@@H](O)C2)cc1)c1nc2ccccc2[nH]1
InChIKey: ULRZEXNCMHFJNG-QZTJIDSGSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.145 nM (pChEMBL 9.84000015258789)
Descriptors: MW 413.48, ALogP 5, HBA 5, HBD 2, PSA 88.1, QED 0.45
Compound (SMILES): CC(=O)N1CC(c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)C1
InChIKey: RRYKCGNPFYSTNW-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.926 nM (pChEMBL 9.029999732971191)
Descriptors: MW 412.45, ALogP 3.93, HBA 5, HBD 1, PSA 88.18, QED 0.5
Compound (SMILES): CC(=O)N1CCC(c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4n3C)cc2)CC1
InChIKey: SUKOBGQTMGSCNU-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 454.53, ALogP 4.72, HBA 6, HBD 0, PSA 77.32, QED 0.41
Compound (SMILES): COc1cnccc1-c1cccnc1Oc1ccc(C(=O)c2nc3ccccc3[nH]2)cc1
InChIKey: WXUBBIPFLOMBBH-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.261 nM (pChEMBL 9.579999923706055)
Descriptors: MW 422.44, ALogP 5.05, HBA 6, HBD 1, PSA 89.99, QED 0.39
Compound (SMILES): O[C@@H]1CCC[C@@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: HHGBPGARRHXTDJ-SJLPKXTDSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 2.86 nM (pChEMBL 8.539999961853027)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@H]2CCC[C@H](O)C2)cc1)c1nc2ccccc2[nH]1
InChIKey: ULRZEXNCMHFJNG-ROUUACIJSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 1.71 nM (pChEMBL 8.770000457763672)
Descriptors: MW 413.48, ALogP 5, HBA 5, HBD 2, PSA 88.1, QED 0.45
Compound (SMILES): Cn1c(C(=O)c2ccc(Oc3ncccc3-c3ccnc(Cl)c3)cc2)nc2ccccc21
InChIKey: ADOHEOHJMNJDJC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 440.89, ALogP 5.71, HBA 6, HBD 0, PSA 69.9, QED 0.26
Compound (SMILES): Cn1c(C(=O)c2ccc(Oc3ncccc3-c3ccnc(F)c3)cc2)nc2ccccc21
InChIKey: SHXHLNKCPTVLFG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 424.44, ALogP 5.19, HBA 6, HBD 0, PSA 69.9, QED 0.29
Compound (SMILES): Cc1cc(-c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4n3C)cc2)ccn1
InChIKey: QYTNRSYCALDEEE-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 6.17 nM (pChEMBL 8.210000038146973)
Descriptors: MW 420.47, ALogP 5.36, HBA 6, HBD 0, PSA 69.9, QED 0.36
Compound (SMILES): c1ccc2sc(Nc3ccc(Oc4ncncc4C4CCOCC4)cc3)nc2c1
InChIKey: KCNCJLQVFVCSGJ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 8.28 nM (pChEMBL 8.079999923706055)
Descriptors: MW 404.5, ALogP 5.52, HBA 7, HBD 1, PSA 69.16, QED 0.47
Compound (SMILES): c1cnc(Oc2ccc(Nc3nc4ccccc4s3)cc2)c([C@@H]2CCCOCC2)c1
InChIKey: MLPSMZMGBDEJHO-QGZVFWFLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 2.79 nM (pChEMBL 8.550000190734863)
Descriptors: MW 417.53, ALogP 6.51, HBA 6, HBD 1, PSA 56.27, QED 0.4