lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)n[nH]1
InChIKey: JRRQXSDUQMJLBB-ZWZZYCPGSA-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 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 472.68, ALogP 5.97, HBA 5, HBD 1, PSA 62.63, QED 0.51
Compound (SMILES): CCc1cnn(-c2cccc(C)n2)c1-c1cc2cnccc2s1
InChIKey: NIQVUPWBHUGPKD-UHFFFAOYSA-N
Target: Transforming growth factor beta-2 proprotein (SINGLE PROTEIN), Homo sapiens
UniProt: P61812
Assay: Inhibition of TGF-beta (unknown origin)
Measurement: IC50 = 4.33 nM (pChEMBL 8.359999656677246)
Descriptors: MW 320.42, ALogP 4.41, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cnc(N4CCCC4C4CCCCN4C)cc2OCC3)n(CC(F)(F)F)n1
InChIKey: BTRBVLVZBYMHDD-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 = 0.106 nM (pChEMBL 9.970000267028809)
Descriptors: MW 516.57, ALogP 3.92, HBA 9, HBD 0, PSA 77.13, QED 0.52
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CCCN(C(C)(C)CO)C4)cc2OCC3)n(C(C)C)n1
InChIKey: MANLYGWZZVOIHV-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 = 0.262 nM (pChEMBL 9.579999923706055)
Descriptors: MW 544.7, ALogP 4.44, HBA 10, HBD 1, PSA 99.05, QED 0.38
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4ccnn4C4CCCN(C(C)(C)CO)C4)cc2OCC3)n(C(C)C)n1
InChIKey: XPPGOMOXJOINTN-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 = 2.01 nM (pChEMBL 8.699999809265137)
Descriptors: MW 530.68, ALogP 4.36, HBA 10, HBD 1, PSA 99.05, QED 0.4
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CCCN(C(C)C)C4)cc2OCC3)n(C(C)C)n1
InChIKey: KIYKQIDKJXPBAJ-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 = 0.293 nM (pChEMBL 9.529999732971191)
Descriptors: MW 514.68, ALogP 5.08, HBA 9, HBD 0, PSA 78.82, QED 0.37
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCC4C4CCN(C)CC4)cc2OCC3)n(C(C)C)n1
InChIKey: HJZZIFQOTCGMQP-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 = 0.419 nM (pChEMBL 9.380000114440918)
Descriptors: MW 461.61, ALogP 4.01, HBA 8, HBD 0, PSA 64.24, QED 0.59
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@@H](C)N4CCN(C(C)(C)C)CC4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: XLJFYTCFZPOLIV-GOSISDBHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as suppression of CD69 expression
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 495.65, ALogP 4.71, HBA 8, HBD 0, PSA 64.24, QED 0.52
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 = 0.735 nM (pChEMBL 9.130000114440918)
Descriptors: MW 516.65, ALogP 4.27, HBA 10, HBD 0, PSA 88.05, QED 0.39
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@@H](C)N4CCN(C(C)(C)C)CC4)c(C)cc2OCC3)n(C(C)C)n1
InChIKey: ROEMKOMVFBZVIY-HXUWFJFHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as suppression of CD69 expression
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 491.68, ALogP 4.88, HBA 8, HBD 0, PSA 64.24, QED 0.52
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@H](C)N4CCN(C(C)(C)C)CC4)ncc2OCC3)n(C(C)C)n1
InChIKey: DKDCWBXTCFPFMR-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as suppression of CD69 expression
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 478.65, ALogP 3.96, HBA 9, HBD 0, PSA 77.13, QED 0.56
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC4C4CCCN(C)C4)cc2OCC3)n(C(C)C)n1
InChIKey: XUSKNOLOZFGDSE-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 = 2.52 nM (pChEMBL 8.600000381469727)
Descriptors: MW 475.64, ALogP 4.4, HBA 8, HBD 0, PSA 64.24, QED 0.56
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC45CCCN(C)C5)cc2OCC3)n(C(C)C)n1
InChIKey: BEPHFNMMVHDLQJ-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 = 0.236 nM (pChEMBL 9.630000114440918)
Descriptors: MW 461.61, ALogP 4.15, HBA 8, HBD 0, PSA 64.24, QED 0.58
Compound (SMILES): CCN(CC)C1CCOC(c2c(-c3ccc4c(c3)OCCn3cc(-c5nc(C)nn5C(C)C)nc3-4)cnn2C)C1
InChIKey: JUCFCEMDRWPMSZ-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 = 0.771 nM (pChEMBL 9.109999656677246)
Descriptors: MW 544.7, ALogP 5.05, HBA 10, HBD 0, PSA 88.05, QED 0.32
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CC(N(C)C(C)C)CCO4)cc2OCC3)n(C(C)C)n1
InChIKey: VVYWQZGWGMFFKQ-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 = 1.23 nM (pChEMBL 8.90999984741211)
Descriptors: MW 544.7, ALogP 5.05, HBA 10, HBD 0, PSA 88.05, QED 0.34
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: ATP-binding cassette sub-family C member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92887
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 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 1216.66
Compound (SMILES): CCC(=O)OCCNC(CC(C)C)C1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: XCAMEKYVLTTXGP-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 38.2 nM (pChEMBL 7.420000076293945)
Descriptors: MW 386.36, ALogP 5.37, HBA 3, HBD 1, PSA 38.33, QED 0.46
Compound (SMILES): CCOc1ccc(C2(C(CC(C)C)NCCOC(=O)CC)CCC2)cc1
InChIKey: GAWYDFHTJQSNCE-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 2340 nM (pChEMBL 5.630000114440918)
Descriptors: MW 361.53, ALogP 4.46, HBA 4, HBD 1, PSA 47.56, QED 0.47
Compound (SMILES): CCOC(=O)NCCNC(CC(C)C)C1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: SBTIZQKJKFHNPY-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 401.38, ALogP 5.17, HBA 3, HBD 2, PSA 50.36, QED 0.56
Compound (SMILES): CCOC(=O)NCCNC(CC(C)C)C1(c2ccc(OCC)cc2)CCC1
InChIKey: BKVALIDOPGIDPZ-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 158.5 nM (pChEMBL 6.800000190734863)
Descriptors: MW 376.54, ALogP 4.26, HBA 4, HBD 2, PSA 59.59, QED 0.57
Compound (SMILES): CCCC(=O)NCCNC(CC(C)C)C1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: ZJFMMMXNSXCMOB-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 52.7 nM (pChEMBL 7.28000020980835)
Descriptors: MW 399.41, ALogP 5.34, HBA 2, HBD 2, PSA 41.13, QED 0.52
Compound (SMILES): CCCC(=O)NCCNC(CC(C)C)C1(c2ccc(OCC)cc2)CCC1
InChIKey: KESMMXPCOOCEDA-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 251.4 nM (pChEMBL 6.599999904632568)
Descriptors: MW 374.57, ALogP 4.43, HBA 3, HBD 2, PSA 50.36, QED 0.53
Compound (SMILES): CC(CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 371.35, ALogP 4.69, HBA 2, HBD 2, PSA 55.12, QED 0.59
Compound (SMILES): C[C@@H](CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-AWEZNQCLSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 30.3 nM (pChEMBL 7.519999980926514)
Descriptors: MW 371.35, ALogP 4.69, HBA 2, HBD 2, PSA 55.12, QED 0.59
Compound (SMILES): C[C@H](CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-CQSZACIVSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 126.1 nM (pChEMBL 6.900000095367432)
Descriptors: MW 371.35, ALogP 4.69, HBA 2, HBD 2, PSA 55.12, QED 0.59
Compound (SMILES): CCOc1ccc(C2(CC(C)CCNCCCC(N)=O)CCC2)cc1
InChIKey: ZEFQZGJPKZZHJW-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 471.6 nM (pChEMBL 6.329999923706055)
Descriptors: MW 346.52, ALogP 3.78, HBA 3, HBD 2, PSA 64.35, QED 0.57
Compound (SMILES): CCOc1ccc(C2(C[C@@H](C)CCNCCCC(N)=O)CCC2)cc1
InChIKey: ZEFQZGJPKZZHJW-KRWDZBQOSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 130.3 nM (pChEMBL 6.880000114440918)
Descriptors: MW 346.52, ALogP 3.78, HBA 3, HBD 2, PSA 64.35, QED 0.57
Compound (SMILES): CCOc1ccc(C2(C[C@H](C)CCNCCCC(N)=O)CCC2)cc1
InChIKey: ZEFQZGJPKZZHJW-QGZVFWFLSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 1086 nM (pChEMBL 5.960000038146973)
Descriptors: MW 346.52, ALogP 3.78, HBA 3, HBD 2, PSA 64.35, QED 0.57
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: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Flu-BakBH3 peptide binding to GST-tagged MCl-1 (unknown origin) after 2 mins by fluorescence polarization assay
Measurement: Ki = 520 nM (pChEMBL 6.28000020980835)
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-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Inhibition Assay: Human recombinant adrenergic β1 receptors expressed in CHO-K1 cells are used in modified Tris-HCl buffer pH 7.4. A 25 aliquot is incubated with 0.03 nM [125I]Cyanopindolol for 120 minutes at 25° C. Non-specific binding is estimated in the presence of 100 μM S(−)-Propranolol. Receptors are filtered and washed, the filters are then counted to determine [125I]Cyanopindolol specifically bound. Compounds are screened at 10 μM.
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 303.36, ALogP 0.53, HBA 5, HBD 2, PSA 85.59, QED 0.77
Compound (SMILES): CC(C)=CCOc1ccc(C2C(=O)N(O)C(=O)/C2=C\C(C)C)cc1
InChIKey: CIBYRBNESSOEJP-WJDWOHSUSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1a (isolate H) (HCV)
UniProt: P27958
Assay: Protease Assay: The HCV protease assay herein was applied to investigate the HCV-protease inhibitory activity of the prepared compounds as described above. The method of the HCV protease assay was described in D. T. Phuong, C. M. Ma, M. Hattori and J. S. J in: Inhibitory Effects of Antrodins A-E from Antrodia cinnamomea and Their Metabolites on Hepatitis C Virus Protease. Phytotherapy Research, 23, 582-584, 2009. Two micro liters of a compound solution (using DMSO as solvent) was placed in 384 well micro plate, then 8 ul of HCV NS3/4A protease (0.5 g/mL) was added to the well containing a sample and the plate was agitated. Finally, 10 uL of freshly prepared substrate (Ac-Asp-Glu-Dap(QXL 520)-Glu-Glu-Abu-COO-Ala-Ser-Cys(5-FAMsp)-NH2) (100 dilution of a DMSO stock solution) was added with sequential rotational shaking. The reaction mixture was incubated for 30 min at 37 C. The fluorimetric analyses were performed on an automated TECAN GENios plate reader with excitation wavelength at 485 nm.
Measurement: IC50 = 16600 nM (pChEMBL 4.78000020980835)
Descriptors: MW 329.4, ALogP 3.46, HBA 4, HBD 1, PSA 66.84, QED 0.39
Compound (SMILES): CC#CCOc1ccc(C(=O)NC[C@@H](C(=O)NO)N2CCN(S(C)(=O)=O)CC2)cc1
InChIKey: GHBQSNPRMVUGFE-KRWDZBQOSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
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 = 6306 nM (pChEMBL 5.199999809265137)
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: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
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 = 2605 nM (pChEMBL 5.579999923706055)
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: Disintegrin and metalloproteinase domain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13443
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): C#Cc1ccc(NC(=O)O[C@H]2C[C@@H](C)C=C3C=C[C@H](C)[C@H](CC[C@@H]4C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O4)[C@H]32)cc1
InChIKey: HWWVAOJWOSZHRO-FIBNWJQGSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Fluorescent Activity Assay: The HDAC activity was performed using the HDAC fluorescent activity assay kit (BIOMOL, Plymouth Meeting, Pa., USA) according to the manufacturer's instructions. Briefly, recombinant proteins of HDAC1 or HDAC6 were incubated with test compounds, and HDAC reaction was initiated by addition of Fluor-de-Lys substrate. Samples were incubated for 10 min at room temperature, followed by adding developer to stop the reaction. Fluorescence was measured by fluorometric reader with excitation at 360 nm and emission at 460 nm. The HDAC activity was expressed as arbitrary fluorescence units (AFU).
Measurement: IC50 = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 577.84
Compound (SMILES): C#Cc1ccc(CNC(=O)O[C@H]2C[C@@H](C)C=C3C=C[C@H](C)[C@H](CC[C@@H]4C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O4)[C@H]32)cc1
InChIKey: YAHJAESFRLNRDH-RZSQEPJQSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Fluorescent Activity Assay: The HDAC activity was performed using the HDAC fluorescent activity assay kit (BIOMOL, Plymouth Meeting, Pa., USA) according to the manufacturer's instructions. Briefly, recombinant proteins of HDAC1 or HDAC6 were incubated with test compounds, and HDAC reaction was initiated by addition of Fluor-de-Lys substrate. Samples were incubated for 10 min at room temperature, followed by adding developer to stop the reaction. Fluorescence was measured by fluorometric reader with excitation at 360 nm and emission at 460 nm. The HDAC activity was expressed as arbitrary fluorescence units (AFU).
Measurement: IC50 = 881.8 nM (pChEMBL 6.050000190734863)
Descriptors: MW 591.87
Compound (SMILES): Cc1ccc(-c2ncccn2)c(C(=O)N2CCC[C@@H](Nc3nc(C)cc(C)n3)[C@@H]2C)c1
InChIKey: QUQAVBRFCYCLKE-GHTZIAJQSA-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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 416.53, ALogP 3.96, HBA 6, HBD 1, PSA 83.9, QED 0.69
Compound (SMILES): C[C@H]1[C@H](Nc2ccc(C(F)(F)F)cn2)CCCN1C(=O)c1ccccc1-n1nccn1
InChIKey: PENQCOARRZDRMK-WMLDXEAASA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
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 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 430.43, ALogP 3.79, HBA 6, HBD 1, PSA 75.94, QED 0.68
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 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 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 444.46, ALogP 4.09, HBA 6, HBD 1, PSA 75.94, QED 0.66
Compound (SMILES): CCOc1ccc(C)nc1C(=O)N1CCC[C@@H](Nc2ccc(C(F)(F)F)cn2)[C@@H]1C
InChIKey: WBNDJIUHFUOZRK-GOEBONIOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
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 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 422.45, ALogP 4.31, HBA 5, HBD 1, PSA 67.35, QED 0.78
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 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 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 445.45, ALogP 3.49, HBA 7, HBD 1, PSA 88.83, QED 0.66
Compound (SMILES): COc1ccc(-n2nccn2)c(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)c1
InChIKey: PMSRTIVUCJNCGM-KBXCAEBGSA-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 = 238 nM (pChEMBL 6.619999885559082)
Descriptors: MW 460.46, ALogP 3.79, HBA 7, HBD 1, PSA 85.17, QED 0.62
Compound (SMILES): Cc1cccc(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)c1-n1nccn1
InChIKey: SJFIWVQBOPVOBS-MAUKXSAKSA-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 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 444.46, ALogP 4.09, HBA 6, HBD 1, PSA 75.94, QED 0.66