lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(CC)C(=O)CN1CC[C@@H](Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: RMSTWPKEPDMVNK-QXGXYANZSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8 nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 μg membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μL binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 30.4 nM (pChEMBL 7.519999980926514)
Descriptors: MW 573.87, ALogP 6.69, HBA 5, HBD 0, PSA 44.61, QED 0.35
Compound (SMILES): c1ccc2c(c1)nc(C[C@H]1COCCN1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: ZFJWLWOSYSURLC-XMVZRQGPSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In Vitro Mu-Opioid Receptor Binding Assay: μ-Opioid Receptor Binding Assay Procedures: Radioligand binding assays were conducted using freshly thawed membranes expressing human μ-receptors (Perkin Elmer, Shelton, Conn.). Radioligand dose-displacement binding assays for human μ-opioid receptors used 0.2 nM [3H]-diprenorphine (NEN, Boston, Mass.), with 5-20 mg membrane protein/well in a final volume of 500 μL, binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hrs at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 5004 of ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50 μL/well), and plates were counted using a Packard Top-Count for 1 min/well. The data were analyzed using the one-site competition curve fitting functions in GraphPad PRISM v. 3.0 (San Diego, Calif.), or an in-house function for one-site competition curve-fitting. for 1 min/well.
Measurement: Ki = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 476.71, ALogP 5.48, HBA 5, HBD 1, PSA 42.32, QED 0.63
Compound (SMILES): O=C(O)CCN1CCC[C@H]1Cc1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: HCRKFMPEDIKLJD-WCSHMYRTSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8 nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 μg membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μL binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 444 nM (pChEMBL 6.349999904632568)
Descriptors: MW 532.77, ALogP 6.43, HBA 5, HBD 1, PSA 61.6, QED 0.44
Compound (SMILES): O=C(O)CN1CCCC[C@H]1Cc1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: DSWUBPMMBDNJSP-WCSHMYRTSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8 nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 μg membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μL binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 169 nM (pChEMBL 6.769999980926514)
Descriptors: MW 532.77, ALogP 6.43, HBA 5, HBD 1, PSA 61.6, QED 0.46
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CC(N(C)C)CCO4)cc2OCC3)n(C(C)C)n1
InChIKey: AYZRGQPKPDHNAX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.864 nM (pChEMBL 9.0600004196167)
Descriptors: MW 516.65, ALogP 4.27, HBA 10, HBD 0, PSA 88.05, QED 0.39
Compound (SMILES): C/C=C/CC(C)C(O)C1C(=O)NC(CC)C(=O)N(C)C(C)C(=O)N(CC)C(C(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(CC(C)C)C(=O)NC(C)C(=O)NC(C)C(=O)N(C)C(CC(C)C)C(=O)N(C)C(CC(C)C)C(=O)N(C)C(C(C)C)C(=O)N1C
InChIKey: OLROWHGDTNFZBH-PBBVDAKRSA-N
Target: Bile salt export pump (SINGLE PROTEIN), Homo sapiens
UniProt: O95342
Assay: Inhibition Assay: To assess the inhibition of the MRP2, MRP3 and BSEP efflux transporters, an in vitro vesicular transporter assay from Solvo Biotechnology Inc. was used. The Test Articles (TAs) (at 0.068, 0.2, 0.62, 1.8, 5.5, 16.7 and 50 uM) were incubated with efflux transporter membrane vesicles (Solvo Biotechnology Inc.) both in the absence and presence of 4 mM ATP to distinguish between transporter mediated uptake and passive diffusion of TA's into the vesicles. In the case of MRP2 and MRP3 transporters reactions were carried out in the presence of 2 mM glutathione. Reaction mixtures were preincubated for ten minutes at 37 C. Reactions were started by the addition of 25 ul of 12 mM MgATP (4 mM final concentration in assay) or assay buffer for background controls. Reactions were stopped by adding 200 ul of ice-cold washing buffer and immediately followed by filtration on glass fiber filters in a 96-well format (filter plate).
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 1216.66
Compound (SMILES): CC(=O)CC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc2cc(O)cc(F)c2)C(=O)N2CCCC(N2)C(=O)O[C@H](/C(C)=C/C=C/C(=O)N2CCCCO2)C/C=C/C=C/[C@H](O)[C@H](C)[C@H]1O
InChIKey: CFLBTKFHBBDVKC-RROFBZPUSA-N
Target: Solute carrier organic anion transporter family member 1B3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPD5
Assay: In Vitro Uptake Transporter Assay: To assess the inhibition of the OAT1B1 and OAT1B3 uptake transporters, an in vitro uptake transporter assay from Solvo Biotechnology Inc. was used. Uptake experiments with Test Article (TA) at 0.068, 0.2, 0.62, 1.8, 5.5, 16.7 and 50 uM, were performed on CHO cells stably expressing human SLC transporters OATP1B1 and OATP1B3. Parental cell line CHO-K was used as negative control. Cells (1x105 in 200 ul 1:1 mixture of Dulbecco's Modified Eagle's Medium and Ham's F-12 DMEM (F-12, Lonza, N.J., US) supplemented with 5 mM sodium butyrate) were plated on standard 96-well tissue culture plates and incubated 24 hours before the experiment at 37 C. in an atmosphere of 5% CO2 and 95% air. Before experiments the medium was aspirated by vacuum suction, cells were washed with 2x100 ul of Krebs-Henseleit buffer pH 7.3 (prepared from Sigma chemicals, Sigma-Aldrich, St Louis, Mo.). Uptake experiments were carried out at 37 C. in 50 ul of Krebs-Henseleit buffer.
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 868.01, ALogP 3.02, HBA 12, HBD 6, PSA 224.14, QED 0.12
Compound (SMILES): Cc1cc2c(C(=O)Cc3ccccc3)c(O)c(O)cc2c(O)c1-c1c(C)cc2c(C(=O)Cc3ccccc3)c(O)c(O)cc2c1O
InChIKey: IDXSKODLTDOMPF-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Isothermal Titration Calorimetry Assays: Titrations were performed using a VP-ITC or ITC200 calorimeter from Microcal (Northampton, Mass.). BCL-XL was used at concentrations between 25 and 100 μM in 20 mM sodium phosphate buffer (pH 7.4) and 5-10% DMSO. Titrants were used at concentrations 10-15× of the protein in the same buffer. Titrations were carried out at 25° C. Data were analyzed using Microcal Origin software provided by the ITC manufacturer (Microcal, Northampton, Mass.).
Measurement: Kd = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 614.65, ALogP 7.36, HBA 8, HBD 6, PSA 155.52, QED 0.08
Compound (SMILES): N#CC1CCCN1C(=O)CNCC(O)COc1ccccc1
InChIKey: IRTKELPEZOBDMX-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Inhibition Assay: Human recombinant adrenergic β2 receptors expressed in CHO cells are used in modified Tris-HCl buffer pH 7.4. A 50 aliquot is incubated with 0.2 nM [3H]CGP-12177 for 60 minutes at 25° C. Non-specific binding is estimated in the presence of 10 μM ICI-118551. Receptors are filtered and washed, the filters are then counted to determine [3H]CGP-12177 specifically bound. Compounds are screened at 10 μM.
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 303.36, ALogP 0.53, HBA 5, HBD 2, PSA 85.59, QED 0.77
Compound (SMILES): CC#CCOc1ccc(C(=O)NC[C@@H](C(=O)NO)N2CCN(S(C)(=O)=O)CC2)cc1
InChIKey: GHBQSNPRMVUGFE-KRWDZBQOSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O14672
Assay: Enzyme Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAMS and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 = 942 nM (pChEMBL 6.03000020980835)
Descriptors: MW 438.51, ALogP -0.73, HBA 7, HBD 3, PSA 128.28, QED 0.28
Compound (SMILES): Cc1cc(COc2ccc(C(=O)NC[C@@H](C(=O)NO)N3CCN(S(C)(=O)=O)CC3)cc2)c2ccccc2n1
InChIKey: PNRXTCCMSJTZGK-DEOSSOPVSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Enzyme Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAMS and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 541.63, ALogP 1.3, HBA 8, HBD 3, PSA 141.17, QED 0.27
Compound (SMILES): O=C(NCC(C(=O)NO)N1CCN(Cc2ccccc2)CC1)c1ccc(OCc2c(C(F)(F)F)nn3ccccc23)cc1
InChIKey: PWHWIWBGOFSUOR-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Enzyme Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAMS and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 596.61, ALogP 3.35, HBA 8, HBD 3, PSA 111.44, QED 0.19
Compound (SMILES): Cc1ccc(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)c(-n2nccn2)c1
InChIKey: ZRBIBMLFZDCZSU-MAUKXSAKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor(Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, IX Pen/Strep, IX sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #1 1039), 10%FBS, IX Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4 C), the supernatant was aspirated and the pellets frozen and stored at -80C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #1 1836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL.
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 444.46, ALogP 4.09, HBA 6, HBD 1, PSA 75.94, QED 0.66
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)n1
InChIKey: DLKBIPTYSSGNMW-GOEBONIOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor(Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, IX Pen/Strep, IX sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #1 1039), 10%FBS, IX Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4 C), the supernatant was aspirated and the pellets frozen and stored at -80C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #1 1836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL.
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 445.45, ALogP 3.49, HBA 7, HBD 1, PSA 88.83, QED 0.66
Compound (SMILES): Cc1ccc(-c2ncco2)c(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)n1
InChIKey: PRBOUMKUMAGYMX-WMLDXEAASA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 445.45, ALogP 4.56, HBA 6, HBD 1, PSA 84.15, QED 0.63
Compound (SMILES): C[C@H]1[C@H](Nc2ccc(Cl)cn2)CCCN1C(=O)c1ccccc1-n1nccn1
InChIKey: MJGKUUKCLJOFTN-WMLDXEAASA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 396.88, ALogP 3.42, HBA 6, HBD 1, PSA 75.94, QED 0.73
Compound (SMILES): C[C@H]1[C@H](Nc2cnc(C(F)(F)F)cn2)CCCN1C(=O)c1ccccc1-n1nccn1
InChIKey: UTXHBVDKNQOXIE-DZGCQCFKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 529 nM (pChEMBL 6.28000020980835)
Descriptors: MW 431.42, ALogP 3.18, HBA 7, HBD 1, PSA 88.83, QED 0.68
Compound (SMILES): O=C(N[C@H]1c2ccccc2OC[C@H]1O)[C@H](Cc1ccccc1)C[C@H](O)CN1CCN(Cc2ccc(-c3ccccn3)o2)C[C@H]1C(=O)NCC(F)(F)F
InChIKey: VJEYRJGOROCIKW-NKDCNHMZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: In vitro inhibition of human liver microsome Cytochrome P450 2D6
Measurement: IC50 = 29600 nM (pChEMBL 4.53000020980835)
Descriptors: MW 721.78, ALogP 3.73, HBA 9, HBD 4, PSA 140.4, QED 0.16
Compound (SMILES): CC(C)(c1ccc(-c2ccncc2)o1)N1CCN(C[C@@H](O)C[C@@H](Cc2ccccc2)C(=O)N[C@H]2c3ccccc3OC[C@H]2O)[C@H](C(=O)NCC(F)(F)F)C1
InChIKey: DYYJWDSYFDXNOW-FLOLVYIHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: In vitro inhibition of human liver microsome Cytochrome P450 3A4
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 749.83, ALogP 4.46, HBA 9, HBD 4, PSA 140.4, QED 0.16
Compound (SMILES): O=C(N[C@H]1c2ccccc2OC[C@H]1O)[C@H](Cc1ccccc1)C[C@H](O)CN1CCN(Cc2ccc(-c3cccnc3)o2)C[C@H]1C(=O)NCC(F)(F)F
InChIKey: MAMJAUDDHCPYJQ-WZXFIOQESA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: In vitro inhibition of human liver microsome Cytochrome P450 2D6
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 721.78, ALogP 3.73, HBA 9, HBD 4, PSA 140.4, QED 0.16
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(OC)=CC3=O)c2cc1OC
InChIKey: NNSKLWXTYRGLMC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 385.38, ALogP 1.64, HBA 9, HBD 1, PSA 108.87, QED 0.54
Compound (SMILES): COc1cc2c(NC3=CC(=O)C(OC(CF)CF)=CC3=O)ncnc2cc1OCC1CCN(C)CC1
InChIKey: FTDHOACXVYZSHC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 502.52, ALogP 3.01, HBA 9, HBD 1, PSA 102.88, QED 0.49
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(SC)=CC3=O)c2cc1OC
InChIKey: DANRECYHPDNQGT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 401.44, ALogP 2.36, HBA 9, HBD 1, PSA 99.64, QED 0.53
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(N4CC(C)OC4=O)=CC3=O)c2cc1OC
InChIKey: WJHGKFUOCDSBSI-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.44, ALogP 1.84, HBA 10, HBD 1, PSA 129.18, QED 0.47
Compound (SMILES): CCC(=O)N1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)CC1
InChIKey: UFLFYKRXLZELNB-SANMLTNESA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of f10a
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 601.69, ALogP 1.72, HBA 7, HBD 3, PSA 170.8, QED 0.2
Compound (SMILES): N=C(N)c1cccc(C[C@H](NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)C(=O)N2CCC(C(=O)NCCN)CC2)c1
InChIKey: ONGKRKOCNOAMPQ-MHZLTWQESA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of matriptase
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 630.73, ALogP 0.95, HBA 8, HBD 5, PSA 205.61, QED 0.13
Compound (SMILES): N=C(N)NCCNC(=O)C1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)CC1
InChIKey: ASERQAPACCCWLA-MHZLTWQESA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin
Measurement: Ki = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 672.77, ALogP 0.47, HBA 8, HBD 7, PSA 241.49, QED 0.07
Compound (SMILES): N=C(N)NCCC(=O)N1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)CC1
InChIKey: BFGMZJACHSZEKY-SANMLTNESA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of matriptase
Measurement: Ki = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 658.74, ALogP 0.18, HBA 8, HBD 6, PSA 232.7, QED 0.1
Compound (SMILES): O=C(O)c1cc(Cc2cc(Cc3ccccc3)c(O)c(C(=O)O)c2)cc(Cc2ccccc2)c1O
InChIKey: BIFGIRDZFXPUKP-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of SHP-1 catalytic domain
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 468.51, ALogP 5.27, HBA 4, HBD 4, PSA 115.06, QED 0.28
Compound (SMILES): C[C@H]1CN(c2cccc3cc(F)ccc23)CCN1CC[C@@H]1OCc2cc(C(N)=O)ccc21
InChIKey: IEEIKXULGHBDHP-GKVSMKOHSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A expressed in LM(tk-) cells
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 433.53, ALogP 4.25, HBA 4, HBD 1, PSA 58.8, QED 0.65
Compound (SMILES): C[C@H]1CN(c2cccc3cc(F)ccc23)CCN1CC[C@H]1OCc2cc(C(N)=O)ccc21
InChIKey: IEEIKXULGHBDHP-SSOJOUAXSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A expressed in LM(tk-) cells
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 433.53, ALogP 4.25, HBA 4, HBD 1, PSA 58.8, QED 0.65
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccc(F)cc1CO)O2)C(C)=CC(C)(C)N3
InChIKey: PNVTUJVNNJCYGM-FMCGGJTJSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity at PR
Measurement: Ki = 970 nM (pChEMBL 6.010000228881836)
Descriptors: MW 459.52, ALogP 6.2, HBA 5, HBD 3, PSA 70.95, QED 0.44
Compound (SMILES): COCOCc1cc(F)ccc1/C=C1\Oc2ccc(O)c(OC)c2-c2ccc3c(c21)C(C)=CC(C)(C)N3
InChIKey: OTWADYHEAKBKQC-MXAYSNPKSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity at PR
Measurement: Ki = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 503.57, ALogP 6.83, HBA 6, HBD 2, PSA 69.18, QED 0.28
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(C)c1)O2)C(C)=CC(C)(C)N3
InChIKey: DPPNIDONMQTQMK-UCQKPKSFSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity at PR
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 425.53, ALogP 6.87, HBA 4, HBD 2, PSA 50.72, QED 0.47
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(C(F)(F)F)c1)O2)C(C)=CC(C)(C)N3
InChIKey: DWKQZGCDDFUDBR-XKZIYDEJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at GR by GRE activation assay relative to Dexamethasone
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 479.5, ALogP 7.58, HBA 4, HBD 2, PSA 50.72, QED 0.4
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(-c4ccccc4)c1)O2)C(C)=CC(C)(C)N3
InChIKey: DPNNWDJFUPUIPT-VEILYXNESA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at GR by GRE activation assay relative to Dexamethasone
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 487.6, ALogP 8.23, HBA 4, HBD 2, PSA 50.72, QED 0.31
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(O)c1)O2)C(C)=CC(C)(C)N3
InChIKey: LEOCLJZACQHETJ-XKZIYDEJSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity at PR
Measurement: Ki = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 427.5, ALogP 6.27, HBA 5, HBD 3, PSA 70.95, QED 0.45
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(OC(F)(F)F)c1)O2)C(C)=CC(C)(C)N3
InChIKey: MDEVKLAGBXBIIK-XKZIYDEJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at GR by GRE activation assay relative to Dexamethasone
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 495.5, ALogP 7.46, HBA 5, HBD 2, PSA 59.95, QED 0.39
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(Oc4ccccc4)c1)O2)C(C)=CC(C)(C)N3
InChIKey: FALVEGVGQPQAJS-VEILYXNESA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at GR by GRE activation assay relative to Dexamethasone
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 503.6, ALogP 8.36, HBA 5, HBD 2, PSA 59.95, QED 0.29
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(-c4ccsc4)c1)O2)C(C)=CC(C)(C)N3
InChIKey: KPICRRQXJIKREI-YSMPRRRNSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at GR by GRE activation assay relative to Dexamethasone
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 493.63, ALogP 8.29, HBA 5, HBD 2, PSA 50.72, QED 0.3
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(-c4cccnc4)c1)O2)C(C)=CC(C)(C)N3
InChIKey: YWUHPEXVOHTAQU-YUMHPJSZSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at GR by GRE activation assay relative to Dexamethasone
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 488.59, ALogP 7.63, HBA 5, HBD 2, PSA 63.61, QED 0.31
Compound (SMILES): O=C1N(Cc2ccc(C(F)(F)F)o2)c2ccccc2[C@]12COc1cc3c(cc12)OCO3
InChIKey: NEBUOXBYNAHKFV-NRFANRHFSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
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 EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Displacement of [3H]prostaglandin E2 from recombinant human full length EP4 receptor expressed in Chem-1 cell membranes after 60 mins by liquid scintillation counting
Measurement: IC50 = 5480 nM (pChEMBL 5.260000228881836)
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 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: GPCR PRESTO-Tango dose-response in antagonist mode with target: S1PR1
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Compound was evaluated for inhibition of human ACHE in an vitro cell free assay measured by absorbance 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 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10276
Assay: Agonist activity at GAL4 DNA-binding domain-tagged RARalpha (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 459.59, ALogP 5.99, HBA 4, HBD 2, PSA 70, QED 0.45
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: Bioactivity Assay: Human kidney embryonic cells HEK-293T were grown in a petri dish (diameter=10 cm) containing DMEM and 10% of bovine fetal serum culture solution, and incubated in an 5% of carbon dioxide-containing incubator at 37° C. Plasmids carrying human URAT1 were transfected to HEK-293T cells using TransIT-293 (Mirus Bio LLC). After 72 hours, the petri dish containing HEK-293T cells transfected with URAT1 was removed from the incubator and the cells were inoculated on Poly-D-Lysine Coated 96-well Plates at a density of 60,000 cells per well. After the cells on the 96-well plates were grown overnight (at least 12 hours) in an incubator at 37 degrees, these cells were gently rinsed 3 times with warm and no chloride ions-containing HBSS buffer (125 mM sodium gluconate, 4.8 mM potassium gluconate, 1.3 mM calcium gluconate, 1.2 mM monopotassium phosphate, 1.2 mM magnesium sulfate, 5.6 mM glucose, 25 mM HEPES, pH 7.4). 50 microliter of HBSS buffer (not containing chloride ions) containing 0.2 microcurie of 14C-uric acid and compounds of the present application or benzbromarone, and vector was added in each well, then the cell plates were put back to the incubator at 37 degrees. After 5 min, the buffer was removed from cell wells, added with 100 microliter of ice-cold and no chloride ions-containing HBSS buffer to gently rinse cells within wells so as to stop them from absorbing 14C-uric acid, the rinsing was repeated 3 times in the same manner. 150 microliter of cell lysate (100 mM of NaOH) was added in each well. Cell plate was placed on a vibrating plate and vibrated for 10 min at a speed of 600 rpm such that the cells were completely lysed. The cell plate was put in a centrifuge and spun for 5 min at a speed of 1000 rpm, then 45 microliter of supernatant was sucked out from each well and transferred to 96-well plate (Isoplate-96 Microplate from PerkinElmer).
Measurement: IC50 < 100 nM (pChEMBL 7)
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: Binding affinity to DNA-tagged recombinant BTK (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd = 21 nM (pChEMBL 7.679999828338623)
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: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Binding affinity towards human NR1I2 in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
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: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P62813
Assay: Binding affinity towards rat Gabra1 in an in vitro assay with cellular components measured by membrane filtration
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 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Inhibition of human Nav1.1 expressed in HEK293 cells co-expressing human beta1 and beta2 assessed as use dependent blocking of late sodium currents at -120 mV holding potential at 10 Hz frequency by whole-cell voltage-clamp method
Measurement: IC50 > 100000 nM (pChEMBL 4)
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] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in baculovirus infected BTI-TN-5B1-4 insect cells using p-tyramine as substrate preincubated for 15 mins and measured after 45 mins by resorufin-based fluorescence assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
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 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at PPARgamma (unknown origin) assessed as transcriptional activation
Measurement: EC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 384.5, ALogP 5.16, HBA 4, HBD 1, PSA 63.6, QED 0.41
Compound (SMILES): O=C(O)CN1CCC[C@H](c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@H]2C[C@@H]3CCC[C@@H](C3)C2)C1
InChIKey: BULRYAVAAXWJIN-NNKIXODWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8 nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 μg membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μL binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 353 nM (pChEMBL 6.449999809265137)
Descriptors: MW 504.72, ALogP 5.83, HBA 5, HBD 1, PSA 61.6, QED 0.56
Compound (SMILES): O=C(O)CN1CCC[C@H]1c1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: CLHWZIKMCHBNFA-FDYHHLSLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro ORL-1 Receptor Binding Assay: ORL-1 Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at −80° C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. The data from screening and dose-displacement experiments were analyzed using Microsoft Excel and the curve fitting functions in GraphPad PRISM¿, v. 3.0, respectively, or an in-house function for one-site competition curve-fitting.
Measurement: Ki = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 504.72, ALogP 6.17, HBA 5, HBD 1, PSA 61.6, QED 0.53
Compound (SMILES): O=C(O)CCN1CCC[C@@H]1c1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: BVKDCVKXPSMBCK-OVZXINRLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Binding Assay: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 518.75, ALogP 6.56, HBA 5, HBD 1, PSA 61.6, QED 0.47
Compound (SMILES): NC(=O)CN1CCC[C@H]1c1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: WGMLKJXEFMLZMR-FDYHHLSLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Binding Assay: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 503.74, ALogP 5.58, HBA 5, HBD 1, PSA 67.39, QED 0.58
Compound (SMILES): O=C(O)CN1CCCC[C@@H]1c1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: RPYQPXALUIMCMA-OVZXINRLSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: In Vitro Kappa-Opioid Receptor Binding Assay: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of kappa receptor membranes were stored at −80° C.Radioligand dose displacement assays used 0.4-0.8 nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 μg membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μL, binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200 μL, ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 518.75, ALogP 6.56, HBA 5, HBD 1, PSA 61.6, QED 0.49
Compound (SMILES): O=C(O)CN1CCC[C@H](c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: FNNTUUAZDHJXRL-JBFJIUAJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Binding Assay: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 518.75, ALogP 6.22, HBA 5, HBD 1, PSA 61.6, QED 0.51
Compound (SMILES): O=C(O)CCN1CCC[C@H](c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: CNXAMMJOFWZPCL-WCSHMYRTSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: In Vitro Kappa-Opioid Receptor Binding Assay: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of kappa receptor membranes were stored at −80° C.Radioligand dose displacement assays used 0.4-0.8 nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 μg membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μL, binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200 μL, ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 532.77, ALogP 6.61, HBA 5, HBD 1, PSA 61.6, QED 0.45