lovingscience/chembl-v37-raw-activities huggingface dataset:
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: 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 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 496.55, ALogP 5.87, HBA 5, HBD 1, PSA 71.77, QED 0.44
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CC(C)(C)C(N)=O)(c2ccccc2)OC1=O
InChIKey: JWNUGQVQBVREKV-WRONEBCDSA-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 = 4.07 nM (pChEMBL 8.390000343322754)
Descriptors: MW 487.6, ALogP 4.75, HBA 5, HBD 1, PSA 94.63, QED 0.52
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(C)c(=O)c2)cc1)N1CC[C@](CC(C)(C)C#N)(c2ccc(F)cc2)OC1=O
InChIKey: CXOMXTMPKJRZRV-WRONEBCDSA-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 487.58, ALogP 5.93, HBA 5, HBD 0, PSA 75.33, QED 0.43
Compound (SMILES): CC(C)[C@@]1(CC(C)(C)O)CCN([C@@H](C)c2ccc(-c3ccn(C)c(=O)c3)cc2)C(=O)O1
InChIKey: FEQAOIMIVXHADA-BVZFJXPGSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 1: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384).
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 426.56, ALogP 4.51, HBA 5, HBD 1, PSA 71.77, QED 0.74
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(C)c(=O)c2)cc1)N1CC[C@](CC(C)(C)O)(C2CC2)OC1=O
InChIKey: BEXKCJWAYLYKOS-GKVSMKOHSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 1: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384).
Measurement: IC50 = 97.49 nM (pChEMBL 7.010000228881836)
Descriptors: MW 424.54, ALogP 4.27, HBA 5, HBD 1, PSA 71.77, QED 0.75
Compound (SMILES): C[C@@H](c1ccc(-c2ccn(CCO)c(=O)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: OQLQWHQAVCHLCZ-LGGPFLRQSA-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 = 7.61 nM (pChEMBL 8.119999885559082)
Descriptors: MW 490.6, ALogP 4.47, HBA 6, HBD 2, PSA 92, QED 0.49
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 1: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384).
Measurement: IC50 = 7.21 nM (pChEMBL 8.140000343322754)
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 1: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384).
Measurement: IC50 = 6.6 nM (pChEMBL 8.180000305175781)
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: 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 = 4.17 nM (pChEMBL 8.380000114440918)
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: 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 = 5.44 nM (pChEMBL 8.260000228881836)
Descriptors: MW 492.59, ALogP 5.44, HBA 5, HBD 1, PSA 71.77, QED 0.45
Compound (SMILES): CC(C)[C@]1(CCCO)CCN([C@@H](C)c2ccc(-c3ccn(C)c(=O)c3)cc2)C(=O)O1
InChIKey: BLIKXDAKWNGQNT-UUOWRZLLSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 1: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384).
Measurement: IC50 = 8.89 nM (pChEMBL 8.050000190734863)
Descriptors: MW 412.53, ALogP 4.12, HBA 5, HBD 1, PSA 71.77, QED 0.74
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)[nH]c2)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
InChIKey: WJULDYZURIKYHG-AFMDSPMNSA-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 = 2.76 nM (pChEMBL 8.5600004196167)
Descriptors: MW 432.52, ALogP 4.61, HBA 4, HBD 2, PSA 82.63, QED 0.57
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
InChIKey: BUIPWQYAVGFZFQ-CCLHPLFOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant CYP3A4 (unknown origin)
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
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: 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 = 11.48 nM (pChEMBL 7.940000057220459)
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: 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 = 3.69 nM (pChEMBL 8.430000305175781)
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)[nH]c2)cc1)N1CC[C@](CCO)(c2ccccc2)OC1=O
InChIKey: GYNKGIGNECUXON-BVZFJXPGSA-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 = 13.62 nM (pChEMBL 7.869999885559082)
Descriptors: MW 418.49, ALogP 4.22, HBA 4, HBD 2, PSA 82.63, QED 0.63
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: 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 = 6.44 nM (pChEMBL 8.1899995803833)
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@](CCCO)(c2ccccc2)OC1=O
InChIKey: WSCJTIAOBWYYJK-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 = 6.75 nM (pChEMBL 8.170000076293945)
Descriptors: MW 446.55, ALogP 4.62, HBA 5, HBD 1, PSA 71.77, QED 0.57
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: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of 11beta-HSD1 in human omental adipocytes using [3H]cortisone as substrate preincubated for 1 hr followed by substrate addition measured after 3 to 4 hrs by scintillation proximity assay
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
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: 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 = 4.02 nM (pChEMBL 8.399999618530273)
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: 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 = 3.96 nM (pChEMBL 8.399999618530273)
Descriptors: MW 454.57, ALogP 5.89, HBA 3, HBD 1, PSA 62.4, QED 0.47
Compound (SMILES): C#CC(C)(C)C[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(-c3ccc(=O)n(C(C)C)c3)cc2)C(=O)O1
InChIKey: AQHGZXDBUOQKOU-BNHRFMORSA-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 = 8.76 nM (pChEMBL 8.0600004196167)
Descriptors: MW 496.65, ALogP 6.94, HBA 4, HBD 0, PSA 51.54, QED 0.33
Compound (SMILES): CCCn1cc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)ccc1=O
InChIKey: YOSFTRKRFZSSDY-CHJDUVSTSA-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 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 488.63, ALogP 5.89, HBA 5, HBD 1, PSA 71.77, QED 0.43
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(CC(C)(C)C)c2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: OVJKEAKWFSJPIU-UDNBHOFDSA-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 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 516.68, ALogP 6.52, HBA 5, HBD 1, PSA 71.77, QED 0.39
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CCCNS(C)(=O)=O)(c2ccc(F)cc2)OC1=O
InChIKey: TXGOQAVJHHSIHI-WTYVLRPYSA-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 = 8.85 nM (pChEMBL 8.050000190734863)
Descriptors: MW 541.65, ALogP 4.32, HBA 6, HBD 1, PSA 97.71, QED 0.41
Compound (SMILES): Cn1c2c(c3cc(S(=O)(=O)c4ccc(C(F)(F)F)cc4)ccc31)C1CCC(C2)N1
InChIKey: VZUXJXGRENJAPJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding Assay: The relative affinities of the various compounds for the 5-HT6 receptor were measured in a radioligand binding assay, using a sintillation proximity assay (SPA) format.
Measurement: Ki = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 420.46, ALogP 4.38, HBA 4, HBD 1, PSA 51.1, QED 0.67
Compound (SMILES): Cn1c2c(c3cc(S(=O)(=O)c4ccc(C#N)cc4)ccc31)C1CCC(C2)N1
InChIKey: HUBRFUMLGFYFAB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding Assay: The relative affinities of the various compounds for the 5-HT6 receptor were measured in a radioligand binding assay, using a sintillation proximity assay (SPA) format.
Measurement: Ki = 747 nM (pChEMBL 6.130000114440918)
Descriptors: MW 377.47, ALogP 3.23, HBA 5, HBD 1, PSA 74.89, QED 0.74
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4ccccn4)n[nH]c3C2(C)C)[C@@H](C)CN1CC1CCOCC1
InChIKey: WIUOWTNXQICTJG-MSOLQXFVSA-N
Target: Serine/threonine-protein kinase PAK 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O96013
Assay: Inhibition of PAK4 Kinase domain (291 to 591 residues) (unknown origin) transfected in TR-293-KDG cells using GEFH1 as substrate assessed as inhibition of PAK4-dependent phosphorylation of GEFH1 at S810 residue incubated for 3 hrs by ELISA
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 495.63, ALogP 3.05, HBA 6, HBD 2, PSA 106.69, QED 0.68
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]nc(-c3ccnc(F)c3)c2cn1)c1ccccc1
InChIKey: ZZXTZVAZXNUZKK-GFCCVEGCSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 376.39, ALogP 4.04, HBA 4, HBD 3, PSA 95.59, QED 0.47
Compound (SMILES): COC(=O)C1CC1c1n[nH]c2cc(NC(=O)N[C@H](C)c3ccccc3)ncc12
InChIKey: NGAGWVSXXQKIEL-LMWSTFAQSA-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 = 1.33 nM (pChEMBL 8.880000114440918)
Descriptors: MW 379.42, ALogP 3.12, HBA 5, HBD 3, PSA 109, QED 0.59
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 = 4.671 nM (pChEMBL 8.329999923706055)
Descriptors: MW 460.51, ALogP 4.98, HBA 5, HBD 3, PSA 104.82, QED 0.39
Compound (SMILES): O=C1c2nnc(-c3ccc(F)cc3)n2CCN1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: LCNBYJZWIZWCKK-UHFFFAOYSA-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 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 424.79, ALogP 4.41, HBA 4, HBD 0, PSA 51.02, QED 0.59
Compound (SMILES): O=C1c2nnc(-c3cnccn3)n2CCN1Cc1cccc(Cl)c1Cl
InChIKey: IHRYBMNZKRJNSI-UHFFFAOYSA-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 = 8670 nM (pChEMBL 5.059999942779541)
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: 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 = 9311.1 nM (pChEMBL 5.03000020980835)
Descriptors: MW 408.77, ALogP 3.06, HBA 6, HBD 0, PSA 76.8, QED 0.67
Compound (SMILES): O=C1c2nnc(-c3ccccn3)n2CCN1Cc1cccc(Cl)c1Cl
InChIKey: UUTDRLSXCYGSLU-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.23, ALogP 3.3, HBA 5, HBD 0, PSA 63.91, QED 0.71
Compound (SMILES): O=C1c2nnc(-c3ccccn3)n2CCN1Cc1cccc(C(F)(F)F)c1Cl
InChIKey: AQOFBMRYRWSLBY-UHFFFAOYSA-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 = 10 nM (pChEMBL 8)
Descriptors: MW 407.78, ALogP 3.67, HBA 5, HBD 0, PSA 63.91, QED 0.66
Compound (SMILES): CC1Cn2c(nnc2-c2cnccn2)C(=O)N1Cc1cccc(Cl)c1Cl
InChIKey: MALWKRIWHLIWMW-UHFFFAOYSA-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 = 300.6 nM (pChEMBL 6.519999980926514)
Descriptors: MW 389.25, ALogP 3.09, HBA 6, HBD 0, PSA 76.8, QED 0.69
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: 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 = 1584.9 nM (pChEMBL 5.800000190734863)
Descriptors: MW 389.25, ALogP 3.09, HBA 6, HBD 0, PSA 76.8, QED 0.69
Compound (SMILES): C[C@H]1Cn2c(nnc2-c2cnccn2)C(=O)N1Cc1cccc(Cl)c1Cl
InChIKey: MALWKRIWHLIWMW-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 = 1.4 nM (pChEMBL 8.850000381469727)
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), 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 = 4 nM (pChEMBL 8.399999618530273)
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), 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 = 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: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Displacement of [3H]JNJ-54232334 from P2X7 receptor in rat hippocampal membranes
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
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: 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 nM (pChEMBL 9)
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), 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 = 350 nM (pChEMBL 6.460000038146973)
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: 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 = 20 nM (pChEMBL 7.699999809265137)
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), 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 = 3.2 nM (pChEMBL 8.489999771118164)
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), 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 nM (pChEMBL 9)
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), 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 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: 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 = 2.5 nM (pChEMBL 8.600000381469727)
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), 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 > 10000 nM (pChEMBL 5)
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), 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 = 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), 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 = 375 nM (pChEMBL 6.429999828338623)
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), 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 = 6.9 nM (pChEMBL 8.15999984741211)
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), 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 = 1.9 nM (pChEMBL 8.720000267028809)
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), 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 = 187.9 nM (pChEMBL 6.730000019073486)
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), 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 = 134.6 nM (pChEMBL 6.869999885559082)
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), 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 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 427.84, ALogP 4.12, HBA 6, HBD 0, PSA 63.91, QED 0.63