lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C(F)F)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: APIRJHBAONBUEP-VKGTZQKMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 496.55, ALogP 5.87, HBA 5, HBD 1, PSA 71.77, QED 0.44
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(C(F)F)c(=O)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: HOIIUDAZGJZKGR-VKGTZQKMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 496.55, ALogP 5.87, HBA 5, HBD 1, PSA 71.77, QED 0.44
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(C)c(=O)c2)cc1)N1CC[C@](C[C@](C)(O)CO)(c2ccccc2)OC1=O
InChIKey: DYEGGIFNESBCIL-IIZLTXOPSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 4: Inhibition assay using 11β-HSD1 in the presence of 50% human plasma.
Measurement: IC50 = 9.58 nM (pChEMBL 8.020000457763672)
Descriptors: MW 476.57, ALogP 3.98, HBA 6, HBD 2, PSA 92, QED 0.54
Compound (SMILES): COC[C@@](C)(O)C[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(-c3ccn(C)c(=O)c3)cc2)C(=O)O1
InChIKey: YCQOHFSEUJSSTM-IZKCBNJNSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 4: Inhibition assay using 11β-HSD1 in the presence of 50% human plasma.
Measurement: IC50 = 20.11 nM (pChEMBL 7.699999809265137)
Descriptors: MW 490.6, ALogP 4.64, HBA 6, HBD 1, PSA 81, QED 0.5
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2F)OC1=O
InChIKey: ZYZZURDCHBXQIE-VKGTZQKMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 478.56, ALogP 5.15, HBA 5, HBD 1, PSA 71.77, QED 0.53
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(CCF)c(=O)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: RBRPBISFBWYXBR-LGGPFLRQSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 492.59, ALogP 5.44, HBA 5, HBD 1, PSA 71.77, QED 0.45
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
InChIKey: BUIPWQYAVGFZFQ-CCLHPLFOSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 4: Inhibition assay using 11β-HSD1 in the presence of 50% human plasma.
Measurement: IC50 = 3.42 nM (pChEMBL 8.470000267028809)
Descriptors: MW 446.55, ALogP 4.62, HBA 5, HBD 1, PSA 71.77, QED 0.57
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: KTNRIRGXBWOYQO-VKGTZQKMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 478.56, ALogP 5.15, HBA 5, HBD 1, PSA 71.77, QED 0.53
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O
InChIKey: NKQLSIVCYOQHSU-UZTOHYMASA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 464.54, ALogP 4.76, HBA 5, HBD 1, PSA 71.77, QED 0.55
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: BFMZBCSQICXEMN-MMTVBGGISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 460.57, ALogP 5.01, HBA 5, HBD 1, PSA 71.77, QED 0.56
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(C)c(=O)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: TXNPQZGSVXLGGP-MMTVBGGISA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 460.57, ALogP 5.01, HBA 5, HBD 1, PSA 71.77, QED 0.56
Compound (SMILES): CC(C)n1cc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)ccc1=O
InChIKey: RPXPOAJHLVZLCE-CHJDUVSTSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 488.63, ALogP 6.06, HBA 5, HBD 1, PSA 71.77, QED 0.44
Compound (SMILES): C#CC(C)(C)C[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(-c3ccc(=O)[nH]c3)cc2)C(=O)O1
InChIKey: UNNIETXFEWYLRH-LGGPFLRQSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 454.57, ALogP 5.89, HBA 3, HBD 1, PSA 62.4, QED 0.47
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)NC4CCCC(Oc5cccc(F)c5)C4)ncc23)ccn1
InChIKey: WNLPPZIAUDXPQQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 51.88 nM (pChEMBL 7.289999961853027)
Descriptors: MW 460.51, ALogP 4.98, HBA 5, HBD 3, PSA 104.82, QED 0.39
Compound (SMILES): O=C1c2nnc(-c3cnccn3)n2CCN1Cc1cccc(Cl)c1Cl
InChIKey: IHRYBMNZKRJNSI-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 438.5 nM (pChEMBL 6.360000133514404)
Descriptors: MW 375.22, ALogP 2.7, HBA 6, HBD 0, PSA 76.8, QED 0.7
Compound (SMILES): O=C1c2nnc(-c3cnccn3)n2CCN1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: MBUOOJUHZJOSRC-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 408.77, ALogP 3.06, HBA 6, HBD 0, PSA 76.8, QED 0.67
Compound (SMILES): C[C@@H]1Cn2c(nnc2-c2cnccn2)C(=O)N1Cc1cccc(Cl)c1Cl
InChIKey: MALWKRIWHLIWMW-SNVBAGLBSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 931.1 nM (pChEMBL 6.03000020980835)
Descriptors: MW 389.25, ALogP 3.09, HBA 6, HBD 0, PSA 76.8, QED 0.69
Compound (SMILES): CC1Cn2c(nnc2-c2cnccn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: FMFQOPWVQJKIAD-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Antagonist activity at rat P2X7 receptor expressed in 1321N1 cells assessed as inhibition of Bz-ATP-induced Ca2+ flux after 30 mins by FLIPR assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 422.8, ALogP 3.45, HBA 6, HBD 0, PSA 76.8, QED 0.65
Compound (SMILES): C[C@@H]1Cn2c(nnc2-c2cnccn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: FMFQOPWVQJKIAD-SNVBAGLBSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 912 nM (pChEMBL 6.039999961853027)
Descriptors: MW 422.8, ALogP 3.45, HBA 6, HBD 0, PSA 76.8, QED 0.65
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cnccn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: FMFQOPWVQJKIAD-JTQLQIEISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 422.8, ALogP 3.45, HBA 6, HBD 0, PSA 76.8, QED 0.65
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccc(F)cc2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: VFMPDKNUENUQPA-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7 receptor expressed in 1321N1 cells assessed as inhibition of Bz-ATP-induced Ca2+ flux after 30 mins by FLIPR assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 438.81, ALogP 4.8, HBA 4, HBD 0, PSA 51.02, QED 0.55
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccccn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: RHOHIFFGKBYPCB-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 FLIPR Assay: 1321N1 cells expressing the recombinant human or rat 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 μl 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 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 316 nM (pChEMBL 6.5)
Descriptors: MW 421.81, ALogP 4.06, HBA 5, HBD 0, PSA 63.91, QED 0.64
Compound (SMILES): Cc1cnc(-c2nnc3n2C[C@H](C)N(Cc2cccc(C(F)(F)F)c2Cl)C3=O)cn1
InChIKey: QKTDNPFNRSPAIL-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 436.83, ALogP 3.76, HBA 6, HBD 0, PSA 76.8, QED 0.62
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ncco2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: QPQDDQHEPCVDSG-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 411.77, ALogP 3.65, HBA 6, HBD 0, PSA 77.05, QED 0.66
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cocn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: ATRGWNSYGHAXFE-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 411.77, ALogP 3.65, HBA 6, HBD 0, PSA 77.05, QED 0.66
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cnco2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: VPBMYOKKNUGDHS-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 411.77, ALogP 3.65, HBA 6, HBD 0, PSA 77.05, QED 0.66
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccn(C)n2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: DDJJWFQUITWZDJ-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7 receptor expressed in 1321N1 cells assessed as inhibition of Bz-ATP-induced Ca2+ flux after 30 mins by FLIPR assay
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 424.81, ALogP 3.4, HBA 6, HBD 0, PSA 68.84, QED 0.65
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cnn(C)c2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: ISYZICSLWWZOAG-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 424.81, ALogP 3.4, HBA 6, HBD 0, PSA 68.84, QED 0.65
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cn[nH]c2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: MVWXAUHJMUOLNW-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 410.79, ALogP 3.38, HBA 5, HBD 1, PSA 79.7, QED 0.72
Compound (SMILES): Cc1cc(-c2nnc3n2C[C@H](C)N(Cc2cccc(C(F)(F)F)c2Cl)C3=O)n[nH]1
InChIKey: QPZFQCMHNZTNCP-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 424.81, ALogP 3.69, HBA 5, HBD 1, PSA 79.7, QED 0.7
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cc[nH]n2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: YHTBIIJNIDNGQA-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 410.79, ALogP 3.38, HBA 5, HBD 1, PSA 79.7, QED 0.72
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cccnc2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: KRUNLDBOHJWLOR-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 421.81, ALogP 4.06, HBA 5, HBD 0, PSA 63.91, QED 0.64
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccc(F)cn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: SMVXSKJUXKNBRG-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 439.8, ALogP 4.2, HBA 5, HBD 0, PSA 63.91, QED 0.57
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2nccs2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: RFWQLMVDRWZVHT-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 427.84, ALogP 4.12, HBA 6, HBD 0, PSA 63.91, QED 0.63
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cscn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: JPXFDKZBXVMECS-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 427.84, ALogP 4.12, HBA 6, HBD 0, PSA 63.91, QED 0.63
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccncn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: ZZMFINHJMAKJAL-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 422.8, ALogP 3.45, HBA 6, HBD 0, PSA 76.8, QED 0.65
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ncc(F)cn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: VDOZEGIWXJADCP-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 440.79, ALogP 3.59, HBA 6, HBD 0, PSA 76.8, QED 0.58
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cc(CO)ccn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: OFTXLJVZPGYWGT-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 451.84, ALogP 3.55, HBA 6, HBD 1, PSA 84.14, QED 0.66
Compound (SMILES): Cc1nc(-c2nnc3n2C[C@H](C)N(Cc2cccc(C(F)(F)F)c2Cl)C3=O)cs1
InChIKey: LYPXELVPVRSISV-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 441.87, ALogP 4.43, HBA 6, HBD 0, PSA 63.91, QED 0.6
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cncs2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: CCBIRAAPSZIYOZ-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 427.84, ALogP 4.12, HBA 6, HBD 0, PSA 63.91, QED 0.63
Compound (SMILES): Cc1nc(C)c(-c2nnc3n2C[C@H](C)N(Cc2cccc(C(F)(F)F)c2Cl)C3=O)s1
InChIKey: KJYCSDWAIHUDNJ-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 22.4 nM (pChEMBL 7.650000095367432)
Descriptors: MW 455.89, ALogP 4.74, HBA 6, HBD 0, PSA 63.91, QED 0.57
Compound (SMILES): Cc1ncsc1-c1nnc2n1C[C@H](C)N(Cc1cccc(C(F)(F)F)c1Cl)C2=O
InChIKey: WDSSYRMOLRKXAI-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 441.87, ALogP 4.43, HBA 6, HBD 0, PSA 63.91, QED 0.6
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccon2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: NDSLFZDEYWBWKR-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 411.77, ALogP 3.65, HBA 6, HBD 0, PSA 77.05, QED 0.66
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ncc(Br)cn2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: RAGJWLIAMKCIPZ-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 501.69, ALogP 4.21, HBA 6, HBD 0, PSA 76.8, QED 0.54
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cncc(F)c2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: WVXNNWPOUGVLSW-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: Radioligand binding: 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 (2.5×)+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 2009, 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 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 439.8, ALogP 4.2, HBA 5, HBD 0, PSA 63.91, QED 0.57
Compound (SMILES): Cc1cccc(-c2nnc3n2C[C@H](C)N(Cc2cccc(C(F)(F)F)c2Cl)C3=O)n1
InChIKey: ZVBBQTJQKQJZEM-LBPRGKRZSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: P2X7 Radioligand Binding: 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 (2.5×)+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). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (K) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human K (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5.
Measurement: Ki = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 435.84, ALogP 4.37, HBA 5, HBD 0, PSA 63.91, QED 0.61
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2ccncc2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: ZKVJGQKRNQLDBN-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca2+ Flux: 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 = 14354.9 nM (pChEMBL 4.840000152587891)
Descriptors: MW 421.81, ALogP 4.06, HBA 5, HBD 0, PSA 63.91, QED 0.64
Compound (SMILES): Cc1ncccc1-c1nnc2n1C[C@H](C)N(Cc1cccc(C(F)(F)F)c1Cl)C2=O
InChIKey: XNCJVYUFVABPQM-NSHDSACASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 13.2 nM (pChEMBL 7.880000114440918)
Descriptors: MW 435.84, ALogP 4.37, HBA 5, HBD 0, PSA 63.91, QED 0.61
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cncc(Cl)c2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: WGMLTKSRZGVBQU-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Antagonist activity at rat P2X7 receptor expressed in 1321N1 cells assessed as inhibition of Bz-ATP-induced Ca2+ flux after 30 mins by FLIPR assay
Measurement: IC50 = 6670 nM (pChEMBL 5.179999828338623)
Descriptors: MW 456.26, ALogP 4.71, HBA 5, HBD 0, PSA 63.91, QED 0.57
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2nccc(C(F)(F)F)n2)C(=O)N1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: OKJDPTYDAZRWKK-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca2+ Flux: 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 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 490.8, ALogP 4.47, HBA 6, HBD 0, PSA 76.8, QED 0.51