lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cnc2[nH]cc(Cc3ccc(NCc4cnccc4C(F)(F)F)nc3F)c2c1
InChIKey: HLNUKOUNRKYWML-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 415.39, ALogP 5.02, HBA 4, HBD 2, PSA 66.49, QED 0.35
Compound (SMILES): FC(F)(F)c1ccncc1CNc1ccc(Cc2c[nH]c3ncc(Cl)cc23)cn1
InChIKey: JOPUUWAQIQBQBZ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.82, ALogP 5.23, HBA 4, HBD 2, PSA 66.49, QED 0.47
Compound (SMILES): Cc1cnc2[nH]cc(Cc3ccc(NCc4ccnc(C)c4)nc3F)c2c1
InChIKey: JEYWLGNUKVSWDE-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 361.42, ALogP 4.31, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): COc1cc(CNc2ccc(Cc3c[nH]c4ncc(C)cc34)c(F)n2)c(F)cn1
InChIKey: IFMNZLKDCPETDL-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 395.41, ALogP 4.15, HBA 5, HBD 2, PSA 75.72, QED 0.48
Compound (SMILES): COc1ncc(CNc2ncc(Cc3c[nH]c4ncc(C)cc34)cn2)cc1F
InChIKey: AHSCWWTXGYZDOT-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.41, ALogP 3.41, HBA 6, HBD 2, PSA 88.61, QED 0.53
Compound (SMILES): Cc1cc(CNc2ccc(Cc3c[nH]c4ncc(Cl)cc34)c(F)n2)ccn1
InChIKey: CCCJZGXGIRJBEW-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 381.84, ALogP 4.66, HBA 4, HBD 2, PSA 66.49, QED 0.49
Compound (SMILES): Cc1cnc2[nH]cc(Cc3cnc(NCc4ccc(C(F)(F)F)nc4)c(F)c3)c2c1
InChIKey: RALYGEAWFFXYBD-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 415.39, ALogP 5.02, HBA 4, HBD 2, PSA 66.49, QED 0.45
Compound (SMILES): Cn1cc(F)cc(CNc2ncc(Cc3c[nH]c4ncc(Cl)cc34)cn2)c1=O
InChIKey: GKKXSXHWFUUCKH-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 398.83, ALogP 3.05, HBA 6, HBD 2, PSA 88.49, QED 0.54
Compound (SMILES): COc1ncc(CNc2ccc(Cc3c[nH]c4ncc(Cl)cc34)c(F)n2)cc1F
InChIKey: ZYUJERAVFWUVMN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 415.83, ALogP 4.5, HBA 5, HBD 2, PSA 75.72, QED 0.45
Compound (SMILES): Fc1cc(Cc2c[nH]c3ncc(Cl)cc23)cnc1NCc1ccc(C(F)(F)F)nc1
InChIKey: PSQZATYJDUBZGN-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 435.81, ALogP 5.37, HBA 4, HBD 2, PSA 66.49, QED 0.41
Compound (SMILES): Clc1cnc2[nH]cc(Cc3ccc(NCc4ccc(Cl)nc4)nc3)c2c1
InChIKey: IHUPHYFSKVFFFO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 384.27, ALogP 4.86, HBA 4, HBD 2, PSA 66.49, QED 0.48
Compound (SMILES): Fc1ccc(CNc2ccc(Cc3c[nH]c4ncc(Cl)cc34)cn2)cn1
InChIKey: QXPPFGDYXVBPPQ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 367.82, ALogP 4.35, HBA 4, HBD 2, PSA 66.49, QED 0.51
Compound (SMILES): COc1ncc(F)cc1CNc1ccc(Cc2c[nH]c3ncc(C#N)cc23)c(F)n1
InChIKey: ADVBAMJDBQBHCU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 406.4, ALogP 3.71, HBA 6, HBD 2, PSA 99.51, QED 0.47
Compound (SMILES): Cc1[nH]nc2c1[C@H](c1ccccc1)C1=C(CC(C)(C)CC1=O)N2
InChIKey: FFFWFAUFYUNHEL-INIZCTEOSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Caliper Assay: A solution of 4× inhibitor (5 μL), 4× substrate/ATP-Metal solution (5 μL), and 2× Kinase solution (10 μL) was prepared with assay buffer (20 mM HEPES, 0.01% Triton X-100, 2 mM DTT, pH 7.5) and mixed/incubated in 384 well plates for 1 or 5 hours depending on the kinase being examined, at room temperature. A solution of termination buffer (QuickScout Screening assist MSA; Carna Biosciences) (60 μL) was added to each well. The entire reaction mixture was then applied to a LabChip3000 system (Caliper Life Science) and the product and substrate peptide peaks were separated and quantified. Evaluation of kinase activity was then determined based on ratio of calculated peak heights of product (P) and substrate (S) peptides (P/(P+S)).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 307.4, ALogP 3.92, HBA 3, HBD 2, PSA 57.78, QED 0.84
Compound (SMILES): COc1ccccc1C1C2=C(CC(C)(C)CC2=O)Nc2n[nH]c(C)c21
InChIKey: KYFJPYWXCUCRPE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: ADP Glo Assay Protocol: 20 μL/well of 4.7 nM GSK3β and 7 μM peptide in KBA (250 mM HEPES (pH 7.5), 50 mM MgCl2, 5 mM EGTA, 0.05% BRIJ-35) were dispensed onto white opaque 384-well plate. 100 nL/well compounds were pinned. 1 μL/well of 140 μM ATP in KBA was dispensed. Incubated at room temperature for 60 minutes. Added 20 μL/well of ADP-glo (Promega, V9103) with Combi, and incubated at room temperature for 40 minutes. Added 40 μL/well of ADP-glo (Promega, V9103) with Combi, incubated at room temperature for 30 minutes. Read on Envision for luminescence.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 337.42, ALogP 3.93, HBA 4, HBD 2, PSA 67.01, QED 0.87
Compound (SMILES): COc1ccccc1C1C2=C(CC(C)(C)CC2=O)Nc2n[nH]c(C(F)(F)F)c21
InChIKey: YWMJEKUKEKXNSA-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: HTS Assay: The GSK3beta primary screen was conducted in assay ready 1536 plates (Aurora 29847) that contain 2.5 mL/well of 10 mM compound. Human GSK3beta as a GST fusion expressed in baculoviral system was purchased from BPS Bioscience (San Diego, Calif.). The GSK3beta peptide substrate was from American Peptide (Sunnyvale, Calif.; Cat 311153). 1 L/well of CABPE (22.5 nM GSK3beta , 8 uM peptide in AB buffer (12.5 mM DTT, 0.25 mg/mL BSA, 0.5 unit/mL Heparin)), 0.5 L/well of 125 uM of ATP, and 1 L/well of positive control 50 uM of GW8510 (positive control) or AB (DMSO only neutral control) in respective wells according to plate design using BioRAPTR (Beckman, Brea, Calif.). Reactions were incubated at room temperature for 60 minutes. 2.5 uL/well of ADP-Glo (Promega, V9103) was added with BioRAPTR, and incubated at room temperature for 40 minutes followed by addition of 5 uL/well of ADP-Glo detection reagent (Promega, V9103) with Combi nL (Thermo, Waltham, Mass.).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 391.39, ALogP 4.64, HBA 4, HBD 2, PSA 67.01, QED 0.78
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2ccccc2)C1
InChIKey: BSHDGRBQTYGFCG-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 1270.6 nM (pChEMBL 5.900000095367432)
Descriptors: MW 417.82, ALogP 5.01, HBA 3, HBD 0, PSA 46.09, QED 0.59
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(ncnc2-c2ccccc2)C1
InChIKey: VCJKLMCWHVGINW-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 95.5 nM (pChEMBL 7.019999980926514)
Descriptors: MW 384.27, ALogP 4.65, HBA 3, HBD 0, PSA 46.09, QED 0.65
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(ncnc2-c2ccn[nH]2)C1
InChIKey: NTUQVIQEPHGASW-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 14.5 nM (pChEMBL 7.840000152587891)
Descriptors: MW 374.23, ALogP 3.37, HBA 4, HBD 1, PSA 74.77, QED 0.75
Compound (SMILES): Cc1c(C(=O)N2CCc3c(ncnc3-c3ccn[nH]3)C2)cccc1C(F)(F)F
InChIKey: HSTYOIFAPJGPSV-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 1011.6 nM (pChEMBL 6)
Descriptors: MW 387.37, ALogP 3.39, HBA 4, HBD 1, PSA 74.77, QED 0.73
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(ncnc2-c2ccccn2)C1
InChIKey: OAMJRWUIWCSIBZ-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 415.9 nM (pChEMBL 6.380000114440918)
Descriptors: MW 385.25, ALogP 4.04, HBA 4, HBD 0, PSA 58.98, QED 0.67
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2ccccn2)C1
InChIKey: GBTQSWFGOHARKG-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 58.9 nM (pChEMBL 7.230000019073486)
Descriptors: MW 418.81, ALogP 4.41, HBA 4, HBD 0, PSA 58.98, QED 0.62
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(ncnc2-c2cnccn2)C1
InChIKey: HWIQIOIKXDRQPK-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 31.6 nM (pChEMBL 7.5)
Descriptors: MW 386.24, ALogP 3.44, HBA 5, HBD 0, PSA 71.87, QED 0.67
Compound (SMILES): Cc1c(C(=O)N2CCc3c(ncnc3-c3cnccn3)C2)cccc1C(F)(F)F
InChIKey: LYSAKHBQGFOSBC-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 399.38, ALogP 3.46, HBA 5, HBD 0, PSA 71.87, QED 0.66
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2ccn[nH]2)C1
InChIKey: DLFARBVDEYIFIT-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 407.78, ALogP 3.74, HBA 4, HBD 1, PSA 74.77, QED 0.7
Compound (SMILES): Cn1ccc(-c2ncnc3c2CCN(C(=O)c2cccc(C(F)(F)F)c2Cl)C3)n1
InChIKey: SPJDIHWFOLGLES-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 26.1 nM (pChEMBL 7.579999923706055)
Descriptors: MW 421.81, ALogP 3.75, HBA 5, HBD 0, PSA 63.91, QED 0.63
Compound (SMILES): O=C(c1ccc(Cl)c(F)c1Cl)N1CCc2c(ncnc2-c2ccn[nH]2)C1
InChIKey: QBRRYFWGWAUOCV-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 392.22, ALogP 3.51, HBA 4, HBD 1, PSA 74.77, QED 0.68
Compound (SMILES): O=C(c1ccc(F)cc1Cl)N1CCc2c(ncnc2-c2ccn[nH]2)C1
InChIKey: GHNPQXLEGZPYHF-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 3213.7 nM (pChEMBL 5.489999771118164)
Descriptors: MW 357.78, ALogP 2.86, HBA 4, HBD 1, PSA 74.77, QED 0.76
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(ncnc2-n2nccn2)C1
InChIKey: KPHGUEVGZGDNLE-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity against ATP-gated P2X7 receptor in LPS-stimulated human whole blood assessed as reduction in P2X7 agonist 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate-induced IL-1beta incubated for 30 mins after 1 hr pre-treatment with LPS followed by Bz-ATP-stimulation for 1.5 hrs by ELISA
Measurement: IC50 = 1122 nM (pChEMBL 5.949999809265137)
Descriptors: MW 375.22, ALogP 2.56, HBA 6, HBD 0, PSA 76.8, QED 0.69
Compound (SMILES): Cc1nc2c(c(-c3ccccc3)n1)CCN(C(=O)c1cccc(Cl)c1Cl)C2
InChIKey: SEOLRANGVFHNBB-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 398.29, ALogP 4.96, HBA 3, HBD 0, PSA 46.09, QED 0.61
Compound (SMILES): Cc1nc2c(c(-c3ccccc3)n1)CCN(C(=O)c1cccc(C(F)(F)F)c1Cl)C2
InChIKey: XSYVNAPPMKTXKO-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human recombinant P2X7 receptor expressed in 1321N1 cells assessed as inhibition of BzATP-induced calcium mobilization incubated for 30 mins measured after 180 seconds by calcium-4 dye based FLIPR assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 431.85, ALogP 5.32, HBA 3, HBD 0, PSA 46.09, QED 0.55
Compound (SMILES): Cc1nc2c(c(-c3ccn[nH]3)n1)CCN(C(=O)c1cccc(C(F)(F)F)c1Cl)C2
InChIKey: QWPHGWGZUGHEEZ-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 1106.6 nM (pChEMBL 5.960000038146973)
Descriptors: MW 421.81, ALogP 4.05, HBA 4, HBD 1, PSA 74.77, QED 0.68
Compound (SMILES): Cc1nc2c(c(-c3ccn[nH]3)n1)CCN(C(=O)c1cccc(Cl)c1Cl)C2
InChIKey: LICQZKIJRJFVOG-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 388.26, ALogP 3.68, HBA 4, HBD 1, PSA 74.77, QED 0.73
Compound (SMILES): Cc1nc2c(c(-c3[nH]ncc3F)n1)CCN(C(=O)c1cccc(C(F)(F)F)c1Cl)C2
InChIKey: GFRAMLAUMXWEGU-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 439.8, ALogP 4.18, HBA 4, HBD 1, PSA 74.77, QED 0.61
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2nccs2)C1
InChIKey: TZGRPXFKIUCAKR-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 12.1 nM (pChEMBL 7.920000076293945)
Descriptors: MW 424.83, ALogP 4.47, HBA 5, HBD 0, PSA 58.98, QED 0.61
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(ncnc2-c2nccs2)C1
InChIKey: WWKIYKPWNKOBLW-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 1377.2 nM (pChEMBL 5.860000133514404)
Descriptors: MW 391.28, ALogP 4.11, HBA 5, HBD 0, PSA 58.98, QED 0.66
Compound (SMILES): Cc1nc2c(c(-c3[nH]ncc3C(F)(F)F)n1)CCN(C(=O)c1cccc(C(F)(F)F)c1Cl)C2
InChIKey: JSBZKBSMSFCJFY-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 489.81, ALogP 5.06, HBA 4, HBD 1, PSA 74.77, QED 0.51
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2ccc[nH]2)C1
InChIKey: ISUSOEMEBZRVAO-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 2511.9 nM (pChEMBL 5.599999904632568)
Descriptors: MW 406.8, ALogP 4.34, HBA 3, HBD 1, PSA 61.88, QED 0.69
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2cscn2)C1
InChIKey: ROMHQZSERGEFTG-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 424.83, ALogP 4.47, HBA 5, HBD 0, PSA 58.98, QED 0.61
Compound (SMILES): Cc1nc2c(c(-c3cscn3)n1)CCN(C(=O)c1cccc(C(F)(F)F)c1Cl)C2
InChIKey: BDYDASKAUVLPBS-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250x the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate.
Measurement: IC50 = 34.8 nM (pChEMBL 7.460000038146973)
Descriptors: MW 438.86, ALogP 4.78, HBA 5, HBD 0, PSA 58.98, QED 0.58
Compound (SMILES): Cc1nc2c(c(-n3nccn3)n1)CCN(C(=O)c1cccc(C(F)(F)F)c1Cl)C2
InChIKey: QEKWDINLYPTBEH-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @ −80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5x)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 39.8 nM (pChEMBL 7.400000095367432)
Descriptors: MW 422.8, ALogP 3.24, HBA 6, HBD 0, PSA 76.8, QED 0.63