lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1[C@H]2c3cc(NCc4ccccc4)ccc3C[C@@H](c3ccc(NCc4ccccc4)cc32)N1CC1CC1
InChIKey: YNFRXLJRYSHXDR-WOGOVJIYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 499.7, ALogP 7.75, HBA 3, HBD 2, PSA 27.3, QED 0.26
Compound (SMILES): CC(=O)N1[C@H](C)[C@H]2c3ccccc3C[C@H]1c1ccccc12
InChIKey: IZQTUVHOVNKEDO-HQOQDVMHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 277.37, ALogP 3.67, HBA 1, HBD 0, PSA 20.31, QED 0.72
Compound (SMILES): COc1cc2c(cc1OC)[C@H]1c3cc(OC)c(OC)cc3[C@H](C2)N(CC2CC2)[C@@H]1C
InChIKey: XGGFHAWXBHYJDK-VZYSNPOVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 409.53, ALogP 4.56, HBA 5, HBD 0, PSA 40.16, QED 0.7
Compound (SMILES): COc1cc2c(cc1OC)[C@H]1c3cc(OC)c(OC)cc3[C@H](C2)N(C)[C@@H]1C
InChIKey: KDHOOJMMEFSELE-WAQMSGSHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 369.46, ALogP 3.78, HBA 5, HBD 0, PSA 40.16, QED 0.82
Compound (SMILES): C[C@@H]1[C@H]2c3cc(N4CCOCC4)ccc3C[C@@H](c3ccc(N4CCOCC4)cc32)N1C
InChIKey: IMJBBDRLBWLKKB-LROUJFHJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.57, ALogP 3.42, HBA 5, HBD 0, PSA 28.18, QED 0.74
Compound (SMILES): C[C@@H]1[C@H]2c3cc(N4CCN(C)CC4)ccc3C[C@@H](c3ccc(N4CCN(C)CC4)cc32)N1C
InChIKey: GAHGDYKRJGEFCV-ANFLZCCJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 445.66, ALogP 3.25, HBA 5, HBD 0, PSA 16.2, QED 0.7
Compound (SMILES): C[C@@H]1[C@H]2c3cc(Nc4ccccc4)ccc3C[C@@H](c3ccc(Nc4ccccc4)cc32)N1C
InChIKey: ZQEXWUJYUSYQRZ-LYWBODIJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 431.58, ALogP 7.24, HBA 3, HBD 2, PSA 27.3, QED 0.36
Compound (SMILES): COc1ccc2c(c1)[C@H]1c3cc(OC)ccc3[C@H](C2)N2CCC[C@@H]12
InChIKey: ZACFCKQGOMIGCS-ACRUOGEOSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 321.42, ALogP 3.91, HBA 3, HBD 0, PSA 21.7, QED 0.84
Compound (SMILES): Brc1ccc2c(c1)[C@H]1c3cc(Br)ccc3[C@H](C2)N2CCC[C@@H]12
InChIKey: UFLBFHHANSUTOM-FHWLQOOXSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 419.16, ALogP 5.42, HBA 1, HBD 0, PSA 3.24, QED 0.55
Compound (SMILES): C[C@@H]1[C@H]2c3ccccc3C[C@@H](c3ccccc32)N1CC1CC1
InChIKey: GIXZRMXKRIPYTJ-OREJSRFESA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 289.42, ALogP 4.53, HBA 1, HBD 0, PSA 3.24, QED 0.78
Compound (SMILES): C=CCN1[C@H](C)[C@H]2c3ccccc3C[C@H]1c1ccccc12
InChIKey: JEFFOQXVZFKCOO-UAOJZALGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 275.39, ALogP 4.31, HBA 1, HBD 0, PSA 3.24, QED 0.74
Compound (SMILES): C[C@@H]1[C@H]2c3ccccc3C[C@@H](c3ccccc32)N1C
InChIKey: GSOKUGXLPOWMGZ-UUWFMWQGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 > 75000 nM (pChEMBL 4.125)
Descriptors: MW 249.36, ALogP 3.75, HBA 1, HBD 0, PSA 3.24, QED 0.69
Compound (SMILES): COc1ccc2c(c1)[C@H]1c3cc(OC)ccc3[C@H](C2)N(CC2CC2)[C@@H]1C
InChIKey: RWIGZHCGPVQFKZ-ILFDSTAHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 5330 nM (pChEMBL 5.269999980926514)
Descriptors: MW 349.47, ALogP 4.55, HBA 3, HBD 0, PSA 21.7, QED 0.81
Compound (SMILES): C[C@@H]1[C@H]2c3cc(NCc4ccccc4)ccc3C[C@@H](c3ccc(NCc4ccccc4)cc32)N1C
InChIKey: DRHSPIUHBMADFT-PDXWSVEKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 459.64, ALogP 6.97, HBA 3, HBD 2, PSA 27.3, QED 0.33
Compound (SMILES): C[C@@H]1[C@H]2c3cc(Nc4ccccc4)ccc3C[C@@H](c3ccc(Nc4ccccc4)cc32)N1CC1CC1
InChIKey: BHKFVMDOGHDESX-ZVMHSHCWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 471.65, ALogP 8.02, HBA 3, HBD 2, PSA 27.3, QED 0.3
Compound (SMILES): O=C1N(Cc2ccc(C(F)(F)F)o2)c2ccccc2[C@]12COc1cc3c(cc12)OCO3
InChIKey: NEBUOXBYNAHKFV-NRFANRHFSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Binding affinity to inactivated state of human Nav1.7 expressed in HEK293 cells by whole cell voltage clamp assay
Measurement: Kd = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 429.35, ALogP 4.25, HBA 5, HBD 0, PSA 61.14, QED 0.61
Compound (SMILES): O=C(O)CNc1cccc(CN(Cc2ccc(-n3cccn3)cc2)S(=O)(=O)c2cccnc2)n1
InChIKey: YHGSTSNEOJUIRN-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at recombinant human EP2 receptor expressed in HEK293 cells assessed as induction of cAMP accumulation after 30 mins
Measurement: EC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 478.53, ALogP 2.55, HBA 8, HBD 2, PSA 130.31, QED 0.36
Compound (SMILES): CC(C)Oc1ccc(-c2nc(-c3cccc4c3CC[C@@H]4NCCO)no2)cc1C#N
InChIKey: XRVDGNKRPOAQTN-FQEVSTJZSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at S1P5 (unknown origin) assessed as stimulation of [35S]GTPgammaS binding incubated for 120 mins in presence of GDP by TopCount scintillation counting method
Measurement: EC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 404.47, ALogP 3.63, HBA 7, HBD 2, PSA 104.2, QED 0.62
Compound (SMILES): O=C([O-])[C@@H]1CCC(O)=N1.O=C([O-])[C@@H]1CCC(O)=N1.[Mg+2]
InChIKey: JQAACYUZYRBHGG-QHTZZOMLSA-L
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Compound was evaluated for inhibition of human KCNH2 in an in vitro assay with cellular components measured by membrane filtration, radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 129.12, ALogP -0.65, HBA 2, HBD 2, PSA 66.4, QED 0.49
Compound (SMILES): CC(C)(C)c1cc(-c2cc(-c3ccc(C(=O)O)cc3)ccc2OCCO)ccc1N1CCCC1
InChIKey: MFBCDACCJCDGBA-UHFFFAOYSA-N
Target: Retinoic acid receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10826
Assay: Activation of RARbeta (unknown origin) expressed in human HeLa cells co-expressing ERE-beta-Glob-Luc-SV-Neo incubated for 18 hrs by luciferase reporter gene assay
Measurement: Kd = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 459.59, ALogP 5.99, HBA 4, HBD 2, PSA 70, QED 0.45
Compound (SMILES): C[C@@H](OC[C@@]1(c2ccccc2)CC[C@]2(CCC(=O)N2)CN1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
InChIKey: FIVSJYGQAIEMOC-ZGNKEGEESA-N
Target: C3a anaphylatoxin chemotactic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16581
Assay: GPCR PRESTO-Tango dose-response in antagonist mode with target: C3AR1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 500.48, ALogP 5.73, HBA 3, HBD 2, PSA 50.36, QED 0.52
Compound (SMILES): CC(C)(Sc1ccncc1-c1ccc(C#N)c2ccccc12)C(=O)O
InChIKey: YYBOLPLTQDKXPM-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition of human URAT1 stably overexpressing in human HEK293 cells assessed as inhibition of 14C-uric acid uptake preincubated for 30 mins followed by substrate addition and measured after 15 mins using 14C-uric acid as substrate by liquid scintillation counting analysis
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 348.43, ALogP 4.73, HBA 4, HBD 1, PSA 73.98, QED 0.69
Compound (SMILES): CC#CC(=O)N1CCC[C@H]1c1nc(-c2ccc(C(=O)Nc3ccccn3)cc2)c2c(N)nccn12
InChIKey: WDENQIQQYWYTPO-IBGZPJMESA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood derived-basophils assessed as suppression of IgE mediated-FcepsilonR ligation-stimulated CD63 expression
Measurement: IC50 = 296.9 nM (pChEMBL 6.53000020980835)
Descriptors: MW 465.52, ALogP 3.31, HBA 7, HBD 2, PSA 118.51, QED 0.45
Compound (SMILES): C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)O
InChIKey: HJCMDXDYPOUFDY-WHFBIAKZSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Binding affinity towards human MC3R in an in vitro assay with cellular components measured by scintillation proximity assay
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 217.22, ALogP -1.83, HBA 4, HBD 4, PSA 135.51, QED 0.41
Compound (SMILES): CN1C(=O)N(C)C2C1N(C)C(=O)N2C
InChIKey: XIUUSFJTJXFNGH-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Compound was evaluated for inhibition of human KCNH2 in an in vitro assay with cellular components measured by membrane filtration, radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 198.23, ALogP -0.37, HBA 2, HBD 0, PSA 47.1, QED 0.53
Compound (SMILES): O=C1c2cc(-c3ccc(OC(F)(F)F)cc3)ccc2OCCN1Cc1ncccn1
InChIKey: YNUAEEJQYHYLMS-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y9
Assay: Inhibition of human NaV1.8 expressed in HEK293 cells co-expressing beta1 sub-units assessed as reduction in peak sodium currents at -100 or -120 mV holding potential and at 25 Hz frequency by whole cell patch-clamp method
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 415.37, ALogP 4.08, HBA 5, HBD 0, PSA 64.55, QED 0.64
Compound (SMILES): CC(=O)N[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
InChIKey: VMAVCCUQTALHOB-INIZCTEOSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P21396
Assay: Inhibition of Sprague-Dawley rat liver MAO-A using p-tyramine as substrate preincubated for 15 mins and measured after 45 mins by resorufin-based fluorescence assay
Measurement: IC50 = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 342.37, ALogP 2.65, HBA 3, HBD 1, PSA 58.64, QED 0.91
Compound (SMILES): CSc1ccc(C(=O)/C=C/c2cc(C)c(OC(C)(C)C(=O)O)c(C)c2)cc1
InChIKey: AFLFKFHDSCQHOL-IZZDOVSWSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human Gal4 fused PPARdelta LBD expressed in COS-7 cells incubated for 24 hrs by firefly luciferase reporter gene assay
Measurement: EC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 384.5, ALogP 5.16, HBA 4, HBD 1, PSA 63.6, QED 0.41
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1.O=C(O)CCCCC(=O)O
InChIKey: CEGWJIQFBNFMHQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): Cc1cccc(NC(=O)c2ccccc2NC(=O)C2CCCCC2)c1
InChIKey: BKPKEVGJQMLUGA-UHFFFAOYSA-N
Target: Relaxin receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBX9
Assay: Agonist activity at human RXFP1 expressed in HEK293 cells assessed as increase in cAMP accumulation after 30 mins by HTRF assay
Measurement: EC50 = 37400 nM (pChEMBL 4.429999828338623)
Descriptors: MW 336.44, ALogP 4.77, HBA 2, HBD 2, PSA 58.2, QED 0.85
Compound (SMILES): Cc1ccc(-c2cc(C(=O)NCc3cnc(C)cn3)cc3c2cnn3CC(C)C)nc1
InChIKey: RVUWCXPMFPPOPU-UHFFFAOYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P49654
Assay: Antagonist activity against rat P2X3 receptor expressed in CHOK1 cells assessed as inhibition of alpha,beta-meATP-induced calcium response incubated for 20 mins by Fluo-3AM dye based FLIPR assay
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 414.51, ALogP 4.09, HBA 6, HBD 1, PSA 85.59, QED 0.51
Compound (SMILES): CCCCn1ncc2c(-c3ccc(C)cn3)cc(C(=O)NCc3cnc(C)cn3)cc21
InChIKey: IDGSUOPUMKFOSU-UHFFFAOYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P49654
Assay: Antagonist activity against rat P2X3 receptor expressed in CHOK1 cells assessed as inhibition of alpha,beta-meATP-induced calcium response incubated for 20 mins by Fluo-3AM dye based FLIPR assay
Measurement: Ki = 41.69 nM (pChEMBL 7.380000114440918)
Descriptors: MW 414.51, ALogP 4.24, HBA 6, HBD 1, PSA 85.59, QED 0.49
Compound (SMILES): CCCNC[C@H](NC(=O)[C@@H](C)c1ccccc1)c1ccc(OC[C@@H](C)CC)cc1
InChIKey: FWPPNWSAQZODQM-SKPFHBQLSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Modulator activity at G-protein-coupled receptor 88 (unknown origin) incubated for 30 mins by cell based cAMP HTRF assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 396.58, ALogP 5.07, HBA 3, HBD 2, PSA 50.36, QED 0.49
Compound (SMILES): COc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c3c(c2Br)CCC3)cc1
InChIKey: YYWOPQSTGZVGOE-IFPLKCGESA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 1.15 nM (pChEMBL 8.9399995803833)
Descriptors: MW 479.37, ALogP 2.05, HBA 6, HBD 4, PSA 99.38, QED 0.52
Compound (SMILES): CCc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c3c(c2Br)CCC3)cc1
InChIKey: MBLHCQNMEPIISC-ZXGKGEBGSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 0.661 nM (pChEMBL 9.180000305175781)
Descriptors: MW 477.4, ALogP 2.61, HBA 5, HBD 4, PSA 90.15, QED 0.53
Compound (SMILES): COc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c3c(c2C)CCC3)cc1
InChIKey: GUKIVDOSBYFYLU-SJSRKZJXSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 1.18 nM (pChEMBL 8.930000305175781)
Descriptors: MW 414.5, ALogP 1.6, HBA 6, HBD 4, PSA 99.38, QED 0.59
Compound (SMILES): COc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c3c(c2Cl)CCCO3)cc1
InChIKey: WYLIOZNHSFRBJY-SQKWCZRTSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 0.978 nM (pChEMBL 9.010000228881836)
Descriptors: MW 450.92, ALogP 1.78, HBA 7, HBD 4, PSA 108.61, QED 0.55
Compound (SMILES): COc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c3c(c2Cl)OCO3)cc1
InChIKey: ADHCAMXJPFDZFV-FTWQHDNSSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 1.15 nM (pChEMBL 8.9399995803833)
Descriptors: MW 438.86, ALogP 1.18, HBA 8, HBD 4, PSA 117.84, QED 0.55
Compound (SMILES): COc1c(C2CCC2)ccc(-c2cnc(N)cn2)c1F
InChIKey: LAMNYGRMYXIUSY-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio.For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values. The letters ND and/or the absence of data in any of the boxes in Table 5 and Table 6 indicates that Ki or IC50 values were not determined.
Measurement: Ki = 52.6 nM (pChEMBL 7.28000020980835)
Descriptors: MW 273.31, ALogP 3.14, HBA 4, HBD 1, PSA 61.03, QED 0.93
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(O)c2F)cn1
InChIKey: BPTQCYJXFAZEKY-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 259.28, ALogP 2.84, HBA 4, HBD 2, PSA 72.03, QED 0.87
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3ccc(C(F)(F)F)cc3)c2F)cn1
InChIKey: PQQXNZPGXARACK-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 417.41, ALogP 5.73, HBA 4, HBD 1, PSA 61.03, QED 0.54
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3cccc(C(F)(F)F)c3)c2F)cn1
InChIKey: JUSBBCOHKYSQQX-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 417.41, ALogP 5.73, HBA 4, HBD 1, PSA 61.03, QED 0.54
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3ccccc3C(F)(F)F)c2F)cn1
InChIKey: QBDKZQKCIRXMDR-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio.For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values. The letters ND and/or the absence of data in any of the boxes in Table 5 and Table 6 indicates that Ki or IC50 values were not determined.
Measurement: Ki = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 417.41, ALogP 5.73, HBA 4, HBD 1, PSA 61.03, QED 0.54
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3cccc(C(=O)O)c3)c2F)cn1
InChIKey: ZMVVONLLQMVZMG-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio.For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values. The letters ND and/or the absence of data in any of the boxes in Table 5 and Table 6 indicates that Ki or IC50 values were not determined.
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 393.42, ALogP 4.41, HBA 5, HBD 2, PSA 98.33, QED 0.64
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3ccc(C(=O)O)cc3)c2F)cn1
InChIKey: HJJKASHLMNAGMC-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 393.42, ALogP 4.41, HBA 5, HBD 2, PSA 98.33, QED 0.64
Compound (SMILES): CS(=O)(=O)c1cccc(COc2c(C3CCC3)ccc(-c3cnc(N)cn3)c2F)c1
InChIKey: CRPOEFMRNMGDEK-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio.For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values. The letters ND and/or the absence of data in any of the boxes in Table 5 and Table 6 indicates that Ki or IC50 values were not determined.
Measurement: Ki = 13.6 nM (pChEMBL 7.869999885559082)
Descriptors: MW 427.5, ALogP 4.11, HBA 6, HBD 1, PSA 95.17, QED 0.64
Compound (SMILES): CS(=O)(=O)c1ccc(COc2c(C3CCC3)ccc(-c3cnc(N)cn3)c2F)cc1
InChIKey: NNAJAQYCJGSMBQ-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 427.5, ALogP 4.11, HBA 6, HBD 1, PSA 95.17, QED 0.64
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3ccccc3OC(F)(F)F)c2F)cn1
InChIKey: MLLUPMLMJWUCNG-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 433.4, ALogP 5.61, HBA 5, HBD 1, PSA 70.26, QED 0.51
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3cccc(OC(F)(F)F)c3)c2F)cn1
InChIKey: WQDVSNBOSDPQSH-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 808 nM (pChEMBL 6.090000152587891)
Descriptors: MW 433.4, ALogP 5.61, HBA 5, HBD 1, PSA 70.26, QED 0.51
Compound (SMILES): CS(=O)(=O)c1cc(Cl)ccc1COc1c(C2CCC2)ccc(-c2cnc(N)cn2)c1F
InChIKey: MODLCJSGJIKCQK-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 461.95, ALogP 4.77, HBA 6, HBD 1, PSA 95.17, QED 0.57
Compound (SMILES): CC(=O)c1ccc(COc2c(C3CCC3)ccc(-c3cnc(N)cn3)c2F)cc1
InChIKey: ONMACCCGOWGGKK-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 391.45, ALogP 4.91, HBA 5, HBD 1, PSA 78.1, QED 0.6
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3cccnc3)c2F)cn1
InChIKey: GIUHENGRAPYLNN-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 350.4, ALogP 4.11, HBA 5, HBD 1, PSA 73.92, QED 0.75
Compound (SMILES): Nc1cnc(-c2ccc(C3CCC3)c(OCc3ccncc3)c2F)cn1
InChIKey: ABJDIJSWCOEPHI-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 350.4, ALogP 4.11, HBA 5, HBD 1, PSA 73.92, QED 0.75
Compound (SMILES): N#Cc1ccc(COc2c(C3CCC3)ccc(-c3cnc(N)cn3)c2F)cc1
InChIKey: DUQKVYHXBZLPMA-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 374.42, ALogP 4.58, HBA 5, HBD 1, PSA 84.82, QED 0.71
Compound (SMILES): N#Cc1cccc(COc2c(C3CCC3)ccc(-c3cnc(N)cn3)c2F)c1
InChIKey: QGKJMGGWRCZZMK-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 374.42, ALogP 4.58, HBA 5, HBD 1, PSA 84.82, QED 0.71