lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(S(C)(=O)=O)ccc1-c1cc(-c2cnnc3c2ncn3C2CC2)ccc1F
InChIKey: HOAUSCIFFXMGAW-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 37.1 nM (pChEMBL 7.429999828338623)
Descriptors: MW 438.48, ALogP 4.05, HBA 7, HBD 0, PSA 86.97, QED 0.47
Compound (SMILES): CCS(=O)(=O)c1ccc(-c2cc(-c3cnnc4c3ncn4C3CC3)ccc2F)c(C#N)c1
InChIKey: HXRKYFIRLIPADY-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 447.5, ALogP 4.3, HBA 7, HBD 0, PSA 101.53, QED 0.45
Compound (SMILES): CC(C)n1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)C(C)C)cc4F)c3)cnnc21
InChIKey: VEIVGFQGXNUAFW-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 87.4 nM (pChEMBL 7.059999942779541)
Descriptors: MW 456.52, ALogP 5.2, HBA 6, HBD 0, PSA 77.74, QED 0.41
Compound (SMILES): COc1cc(S(=O)(=O)C(C)C)ccc1-c1cc(-c2cnnc3c2ncn3C(C)C)ccc1F
InChIKey: ZACRDHYLVQJELO-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 468.55, ALogP 5.07, HBA 7, HBD 0, PSA 86.97, QED 0.39
Compound (SMILES): COc1cc(S(C)(=O)=O)ccc1-c1cc(-c2cnnc3c2ncn3C(C)C)ccc1F
InChIKey: ATANXXIRELYOTO-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 8.56 nM (pChEMBL 8.069999694824219)
Descriptors: MW 440.5, ALogP 4.29, HBA 7, HBD 0, PSA 86.97, QED 0.46
Compound (SMILES): CCS(=O)(=O)c1ccc(-c2cc(-c3cnnc4c3ncn4C(C)C)ccc2F)c(Cl)c1
InChIKey: AUSBOPQXKDERQI-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 458.95, ALogP 5.33, HBA 6, HBD 0, PSA 77.74, QED 0.4
Compound (SMILES): CCS(=O)(=O)c1ccc(-c2cc(-c3cnnc4c3ncn4C(C)C)ccc2F)c(OC)c1
InChIKey: IIEQMDVLVGLCGV-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 454.53, ALogP 4.68, HBA 7, HBD 0, PSA 86.97, QED 0.42
Compound (SMILES): CCS(=O)(=O)c1ccc(-c2cc(-c3cnnc4c3ncn4C(C)C)ccc2F)c(C#N)c1
InChIKey: IPMZGTIZOICFFI-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 29.1 nM (pChEMBL 7.539999961853027)
Descriptors: MW 449.51, ALogP 4.55, HBA 7, HBD 0, PSA 101.53, QED 0.44
Compound (SMILES): CCCCCCCCCCc1nc(N2C(C)CCC2C)nc(C)c1O
InChIKey: TYRRVLIAEQXQEB-UHFFFAOYSA-N
Target: NADH-ubiquinone oxidoreductase chain 1 (SINGLE PROTEIN), Bos taurus
UniProt: P03887
Assay: Inhibition Assay: Beef heart mitochondria were obtained by a large-scale procedure. Inverted submitochondrial particles (SMP) were prepared by the method of Matsuno-Yagi and Hatefi (J. Biol. Chem. 260 (1985), p. 14424), and stored in a buffer containing 0.25 M sucrose and 10 mM Tris-HCl (pH 7.4) at −80° C. Inhibitory effects of compounds on bovine heart mitochondrial complex (I, III, IV) were evaluated. Maximal dimethyl sulfoxide concentration never exceeded 2% and had no influence on the control enzymatic activity. Beef heart SMP were diluted to 0.5 mg/mL. The enzymatic activities were assayed at 30° C. and monitored spectrophotometrically with a Beckman Coulter DU-530 (340 nm, c=6.22 mM−1 cm−1). NADH oxidase activity was determined in a reaction medium (2.5 mL) containing 50 mM Hepes, pH 7.5, containing 5 mM MgCl2. The final mitochondrial protein concentration was 30 μg.
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 347.55, ALogP 5.55, HBA 4, HBD 1, PSA 49.25, QED 0.56
Compound (SMILES): COC[C@H](N)CNc1ncc(C(N)=O)c(Nc2cccc(C)c2)n1
InChIKey: FHPRHJKNEQEXFG-LLVKDONJSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition Assay: SYK tyrosine phosphorylation activity is measured using the LANCE Technology developed by Perkin Elmer Life and Analytical Sciences (Boston, Mass.). LANCE refers to homogeneous time resolved fluorometry applications using techniques such as time-resolved fluorescence resonance energy transfer assay (TR-FRET) (see generally for procedures in Perkin Elmer Application Note How to Optimize a Tyrosine Kinase Assay Using Time Resolved Fluorescence-Based LANCE Detection, wwww.perkinelmer.com/lifesciences). The assay principle involves detection of a phosphorylated substrate using energy transfer from a phosphospecific europium-labeled antibody to streptavidin-allophycocyanin as an acceptor.To test the ability of candidate molecules to inhibit SYK tyrosine phosphorylation activity, molecules are reconstituted in 30% DMSO and serially diluted 1:3 with the final dilution containing DMSO in the absence of the candidate molecule. The final DMSO concentration in the assay is 3%.
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 330.39, ALogP 1.01, HBA 7, HBD 4, PSA 128.18, QED 0.57
Compound (SMILES): Cc1ccnc(N[C@H]2CC[C@H](Oc3ncccc3C3CCOCC3)CC2)c1
InChIKey: CRQYLZWGTOUQFP-WGSAOQKQSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 367.49, ALogP 4.48, HBA 5, HBD 1, PSA 56.27, QED 0.84
Compound (SMILES): Cc1cccnc1N[C@H]1CC[C@H](Oc2ncccc2C2CCOCC2)CC1
InChIKey: CBQDVQFSGGVVFK-WGSAOQKQSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 367.49, ALogP 4.48, HBA 5, HBD 1, PSA 56.27, QED 0.84
Compound (SMILES): Cc1cccc(N[C@H]2CC[C@H](Oc3ncccc3C3CCOCC3)CC2)n1
InChIKey: JWEPAMHMLLKDFA-WGSAOQKQSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 367.49, ALogP 4.48, HBA 5, HBD 1, PSA 56.27, QED 0.84
Compound (SMILES): c1cnc(O[C@H]2CC[C@H](Nc3ccc4ccccc4n3)CC2)c(C2CCOCC2)c1
InChIKey: HMSDHLOVHPXKJR-MEMLXQNLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 403.53, ALogP 5.33, HBA 5, HBD 1, PSA 56.27, QED 0.62
Compound (SMILES): c1cnc(O[C@H]2CC[C@H](Nc3nc4ccccc4o3)CC2)c(C2CCOCC2)c1
InChIKey: CLFVSSFLJIOXPR-IYARVYRRSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 393.49, ALogP 4.92, HBA 6, HBD 1, PSA 69.41, QED 0.66
Compound (SMILES): c1cnc(O[C@H]2CC[C@H](Nc3nc4ccccc4s3)CC2)c(C2CCOCC2)c1
InChIKey: OKZBLGFVGYBKQM-IYARVYRRSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 32.52 nM (pChEMBL 7.489999771118164)
Descriptors: MW 409.56, ALogP 5.39, HBA 6, HBD 1, PSA 56.27, QED 0.61
Compound (SMILES): Cc1ccc(N[C@H]2C[C@H](Oc3ncccc3C3CCOCC3)C2)nc1
InChIKey: IDVOWFCUTYLYRH-QAQDUYKDSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 17.63 nM (pChEMBL 7.75)
Descriptors: MW 339.44, ALogP 3.7, HBA 5, HBD 1, PSA 56.27, QED 0.9
Compound (SMILES): Cc1ccc(N[C@H]2C[C@@H](Oc3ncccc3C3CCOCC3)C2)nc1
InChIKey: IDVOWFCUTYLYRH-CALCHBBNSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 8.249 nM (pChEMBL 8.079999923706055)
Descriptors: MW 339.44, ALogP 3.7, HBA 5, HBD 1, PSA 56.27, QED 0.9
Compound (SMILES): CC(=O)N1CCC(c2nccnc2O[C@H]2C[C@@H](Nc3nc4ccccc4s3)C2)CC1
InChIKey: NEQMSIHABJJZOZ-CALCHBBNSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 2.766 nM (pChEMBL 8.5600004196167)
Descriptors: MW 423.54, ALogP 3.83, HBA 7, HBD 1, PSA 80.24, QED 0.67
Compound (SMILES): CC(=O)N1CCC(c2nccnc2O[C@H]2C[C@H](Nc3ccc4ccccc4n3)C2)CC1
InChIKey: UUKCBNBPKAEKBA-MXVIHJGJSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 15.82 nM (pChEMBL 7.800000190734863)
Descriptors: MW 417.51, ALogP 3.77, HBA 6, HBD 1, PSA 80.24, QED 0.68
Compound (SMILES): O=C(c1ccccn1)C1CC(Oc2ncccc2C2CCOCC2)C1
InChIKey: CIJFGRDZTRVOCJ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 249.6 nM (pChEMBL 6.599999904632568)
Descriptors: MW 338.41, ALogP 3.41, HBA 5, HBD 0, PSA 61.31, QED 0.78
Compound (SMILES): CC(=O)N1CCC(c2nccnc2O[C@H]2C[C@@H](Nc3ccc(C)cn3)C2)CC1
InChIKey: GOOOWYZSQWBVDW-HDICACEKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 66.06 nM (pChEMBL 7.179999828338623)
Descriptors: MW 381.48, ALogP 2.93, HBA 6, HBD 1, PSA 80.24, QED 0.86
Compound (SMILES): CC(=O)N1CCC(c2nccnc2O[C@H]2C[C@H](Nc3ccc(C)cn3)C2)CC1
InChIKey: GOOOWYZSQWBVDW-IYARVYRRSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 84.55 nM (pChEMBL 7.070000171661377)
Descriptors: MW 381.48, ALogP 2.93, HBA 6, HBD 1, PSA 80.24, QED 0.86
Compound (SMILES): c1cnc(O[C@H]2C[C@@H](Nc3nc4ccccc4[nH]3)C2)c(C2CCOCC2)c1
InChIKey: CNRUVGBQIUTQMP-IYBDPMFKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 1.529 nM (pChEMBL 8.819999694824219)
Descriptors: MW 364.45, ALogP 3.87, HBA 5, HBD 2, PSA 72.06, QED 0.72
Compound (SMILES): c1cnc(O[C@H]2C[C@H](Nc3nc4ccccc4[nH]3)C2)c(C2CCOCC2)c1
InChIKey: CNRUVGBQIUTQMP-WKILWMFISA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 2.627 nM (pChEMBL 8.579999923706055)
Descriptors: MW 364.45, ALogP 3.87, HBA 5, HBD 2, PSA 72.06, QED 0.72
Compound (SMILES): CC(=O)N1CCC(c2nccnc2O[C@H]2CC[C@H](Nc3nc4ccccc4s3)CC2)CC1
InChIKey: WILXNMBMGZUKIZ-WGSAOQKQSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 45.51 nM (pChEMBL 7.340000152587891)
Descriptors: MW 451.6, ALogP 4.61, HBA 7, HBD 1, PSA 80.24, QED 0.61
Compound (SMILES): c1cnc(O[C@H]2C[C@H](Nc3nc4ccccc4s3)C2)c(C2CCOCC2)c1
InChIKey: TWASZFQBSIKKST-WKILWMFISA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 3.195 nM (pChEMBL 8.5)
Descriptors: MW 381.5, ALogP 4.61, HBA 6, HBD 1, PSA 56.27, QED 0.7
Compound (SMILES): c1cnc(O[C@H]2C[C@@H](Nc3nc4ccccc4s3)C2)c(C2CCOCC2)c1
InChIKey: TWASZFQBSIKKST-IYBDPMFKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 0.751 nM (pChEMBL 9.119999885559082)
Descriptors: MW 381.5, ALogP 4.61, HBA 6, HBD 1, PSA 56.27, QED 0.7
Compound (SMILES): Fc1cccc2sc(N[C@H]3C[C@@H](Oc4nccnc4C4CCOCC4)C3)nc12
InChIKey: KPNVMKSCNLFPRS-OKILXGFUSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 400.48, ALogP 4.14, HBA 7, HBD 1, PSA 69.16, QED 0.69
Compound (SMILES): Fc1ccc2sc(N[C@H]3C[C@@H](Oc4nccnc4C4CCOCC4)C3)nc2c1
InChIKey: TXGAWYPDMPNVQN-GASCZTMLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 18.3 nM (pChEMBL 7.739999771118164)
Descriptors: MW 400.48, ALogP 4.14, HBA 7, HBD 1, PSA 69.16, QED 0.69
Compound (SMILES): Fc1ccc2nc(N[C@H]3C[C@@H](Oc4nccnc4C4CCOCC4)C3)sc2c1
InChIKey: OGTJZDFPHVSLAB-GASCZTMLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 400.48, ALogP 4.14, HBA 7, HBD 1, PSA 69.16, QED 0.69
Compound (SMILES): Fc1cccc2nc(N[C@H]3C[C@@H](Oc4nccnc4C4CCOCC4)C3)sc12
InChIKey: ZRKYUHLMVQANIB-OKILXGFUSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 27.1 nM (pChEMBL 7.570000171661377)
Descriptors: MW 400.48, ALogP 4.14, HBA 7, HBD 1, PSA 69.16, QED 0.69
Compound (SMILES): Fc1cnc(O[C@H]2C[C@@H](Nc3nc4c(F)cccc4s3)C2)c(C2CCOCC2)c1
InChIKey: MYZANFCECGBUEJ-GASCZTMLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 5.43 nM (pChEMBL 8.270000457763672)
Descriptors: MW 417.48, ALogP 4.89, HBA 6, HBD 1, PSA 56.27, QED 0.64
Compound (SMILES): Fc1cnc(O[C@H]2C[C@@H](Nc3nc4cc(F)ccc4s3)C2)c(C2CCOCC2)c1
InChIKey: QQEZYOZHXMHUJP-IYBDPMFKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 3.49 nM (pChEMBL 8.460000038146973)
Descriptors: MW 417.48, ALogP 4.89, HBA 6, HBD 1, PSA 56.27, QED 0.64
Compound (SMILES): Fc1cnc(O[C@H]2C[C@@H](Nc3nc4ccc(F)cc4s3)C2)c(C2CCOCC2)c1
InChIKey: WQOWYXXNGDDDAY-IYBDPMFKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 1.44 nM (pChEMBL 8.84000015258789)
Descriptors: MW 417.48, ALogP 4.89, HBA 6, HBD 1, PSA 56.27, QED 0.64
Compound (SMILES): Fc1cnc(O[C@H]2C[C@@H](Nc3nc4cccc(F)c4s3)C2)c(C2CCOCC2)c1
InChIKey: DBBHHBCZOVDEQH-GASCZTMLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL, of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL, of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The 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.).Enzyme Inhibition. To check the inhibition profile, 5 uL, of serial diluted compounds were incubated with 5 uL, of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 2.45 nM (pChEMBL 8.609999656677246)
Descriptors: MW 417.48, ALogP 4.89, HBA 6, HBD 1, PSA 56.27, QED 0.64