lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)C/C=C/C(=O)N1CCOc2c1ccc1ncnc(Nc3ccc(OCc4ccc(F)cc4)cc3)c21
InChIKey: PKWKXKSHOMWEQD-ONEGZZNKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR and HER2 Kinase Activity Assay: The assay for the inhibition of EGFR and HER2 kinase activity by small molecular compounds was carried out using the method as follows:1) Dilution of the compoundsIn a 96-well plate a, the compounds were diluted with DMSO using a 3-fold gradient dilution to form 11 concentrations, the 12th concentration is pure DMSO (as a positive control); and in a new 96-well plate b the above solutions were diluted 25 times with ultrapure water (DMSO concentration is 4%).2) Transferring the compounds to 384-well plateThe compound solutions diluted with ultrapure water in the 96-well plate b above was transferred to the corresponding wells of a 384-well plate in duplicate.3) Addition of 4×kinase solution: 2.5 μl of the above 4× kinase solution was taken using multichannel pipette and added to the corresponding reaction wells of the 384-well plate, mixed well and pre-reacted at room temperature for 5 minutes.4) Addition of 2×substrate/ATP mixed solution: 5 μl of the above 2×substrate/ATP mixed solution was taken using multichannel pipette and added to the corresponding reaction wells of the 384-well plate.5) Negative control: negative control wells were set in the 384-well plate, and 2.5 μl 4×substrate, 2.5 μl 4×enzyme solution, 2.5 μl 1×Kinase Assay Buffer and 2.5 μl ultrapure water containing 4% DMSO were added to each well.6) Mixed by centrifugation and kept at room temperature for 2 hours in the dark.7) Termination of the enzymatic reaction:5 μl of the above 4× stop solution was pipetted to the corresponding wells of the 384-well plate, centrifuged and mixed, and reacted at room temperature for 5 minutes.8) Development reaction:5 μl of the above 4× detection solution was pipetted into the corresponding wells of the 384-well plate, centrifuged and mixed, and reacted at room temperature for 1 hour.9) The 384-well plate was placed into a microplate reader and the signal was detected using the corresponding program.10) IC50 analysis:Well reading value=10000*EU665 value/EU615 valueInhibition rate=(reading value of positive control well−reading value of experimental well)/(reading value of positive control well−reading value of negative control well)*100%Corresponding IC50s can be calculated by entering the drug concentrations and the corresponding inhibition rates into GraphPad Prism 5.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 513.57, ALogP 4.93, HBA 7, HBD 1, PSA 79.82, QED 0.33
Compound (SMILES): CC(C)OC(=O)Cn1cc(Nc2ncc3ccn(C[C@@H](CCN(C)C)C(C)C)c3n2)cn1
InChIKey: PXBFZTIBZNKVEF-LJQANCHMSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK/TYK2 Assay: 10 mM test compound stock or 1 mM control compound stock (tofocitinib, ruxolitinib or staurosporine) in DMSO was diluted to 0.4 mM in DMSO. A 3-fold series dilution was then performed in DMSO to generate 10 different compound concentrations. The assay was carried out in 384-well white plate. 0.5 uL of 40× compound DMSO solution at different concentrations was mixed with 10 uL 2× enzyme prepared in reaction buffer (20 mM HEPES, 10 mM MgCl2, 0.01% Tween, 1 mM DTT, pH 7.5). 10 uL 2× substrate mixture prepared in reaction buffer was then added to start the reaction. A short spin was done to settle down all solutions to the bottom of the plate. Final concentrations of test compound in the reaction mixture were 10000, 3333, 1111, 370, 123, 41.2, 13.7, 4.57, 1.52and 0.51 nM. Concentrations of control compound were ten times less. Enzymatic reaction was conducted at 25° C. for 1-2 hours. 10 uL of Kinase Glo Reagents was added to stop the reaction and generate the luminescent signal which was measured using Envision. Luminescence signal was inversely related to kinase activity. Reaction mixture which did not contain enzyme served as negative control. The mixture without any compound was the positive control.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 441.58, ALogP 3.55, HBA 9, HBD 1, PSA 90.1, QED 0.46
Compound (SMILES): C[C@@H](c1ccc(C(F)(F)F)nc1)n1nc(C#N)c2c(=O)[nH]c(C3CCC3c3ncc(C4CC4)cn3)nc21
InChIKey: IZUNLAVGPGXIDZ-CDEQTRAXSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Enzyme Assay: Assays for PDE 1 through 11 were performed in parallel at room temperature in 384-well microtiter plates with an incubation volume of 20.2 μL. Solutions of test compounds were prepared in DMSO and serially diluted with DMSO to yield 30 μL of each of ten solutions differing by 3-fold in concentration, at 32 serial dilutions per plate. 100% inhibition was determined by adding buffer in place of the enzyme and 0% inhibition is determined by using DMSO (1% final concentrations). A Labcyte POD 810 (Labcyte, Sunnyvale, Calif.) was used to dispense 200 nL from each well of the titration plate to make eleven copies of the assay plate for each titration, one copy for each PDE enzyme. A solution of each enzyme (dilution from aliquots, sufficient to produce 20% substrate conversion) and a separate solution of FAM-labeled cAMP or FAM-labeled cGMP from Molecular Devices (Sunnyvale, Calif., product # R7506 or cGMP#R7508), at a final concentration of 50 nM were made in the assay buffer (10 mM Tris HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3 0.01% Tween-20, and 1 mM DTT). Note that the substrate for PDE2 is 50 nM FAM cAMP containing 1000 nM of cGMP. The enzyme and the substrate were then added to the assay plates in two consecutive additions of 10 μL and then shaken to mix. The reaction was allowed to proceed at room temperature for 60 minutes. A binding solution was then made from the kit components, comprised of 80% Solution A, 20% Solution B and binding reagent at a volume of 1/600 the total binding solution. The enzymatic reaction was stopped by addition of 60 μL of the binding solution to each well of the assay plate. The plates were sealed and shaken for 10 seconds
Measurement: Ki = 0.01 nM (pChEMBL 11)
Descriptors: MW 506.49, ALogP 4.34, HBA 8, HBD 1, PSA 126.03, QED 0.43
Compound (SMILES): O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
InChIKey: GZCGUPFRVQAUEE-KCDKBNATSA-N
Target: PA-I galactophilic lectin (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228)
UniProt: Q05097
Assay: Binding affinity to Pseudomonas aeruginosa PAO1 LecA assessed as dissociation constant
Measurement: Kd = 87500 nM (pChEMBL 4.059999942779541)
Descriptors: MW 180.16, ALogP -3.38, HBA 6, HBD 5, PSA 118.22, QED 0.28
Compound (SMILES): C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C=O
InChIKey: PNNNRSAQSRJVSB-KCDKBNATSA-N
Target: Fucose-binding lectin PA-IIL (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
UniProt: Q9HYN5
Assay: Inhibition of Pseudomonas aeruginosa LecB by fluorescence polarization assay
Measurement: IC50 = 2740 nM (pChEMBL 5.559999942779541)
Descriptors: MW 164.16, ALogP -2.35, HBA 5, HBD 4, PSA 97.99, QED 0.35
Compound (SMILES): CN(C(=O)Cc1ccc(Cl)c(Cl)c1)C1CCCCC1N1CCCC1.CS(=O)(=O)O
InChIKey: OJPHNZCUXUUVKU-UHFFFAOYSA-N
Target: Peripheral myelin protein 22 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01453
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Modulators of Human Peripheral Myelin Protein 22 (PMP22) Expression/Activity. (Class of assay: confirmatory) 
Measurement: Potency = 67455.5 nM (pChEMBL 4.170000076293945)
Descriptors: MW 369.34, ALogP 4.4, HBA 2, HBD 0, PSA 23.55, QED 0.79
Compound (SMILES): Cl.Cl.Fc1ccc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)cc1.Fc1ccc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)cc1.O
InChIKey: MQZOATSIFWSKKT-OASXIEIISA-N
Target: Nuclear factor NF-kappa-B p105 subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P19838
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Identification of Small Molecule Agonists for NFkB Signaling Pathway. (Class of assay: confirmatory) [Related pubchem assays: 895 ]
Measurement: Potency = 10000 nM (pChEMBL 5)
Descriptors: MW 329.37, ALogP 3.33, HBA 4, HBD 1, PSA 39.72, QED 0.93
Compound (SMILES): CN(C(=O)Cc1ccc(Cl)c(Cl)c1)C1CCCCC1N1CCCC1.Cl
InChIKey: KGMMGVIYOHGOKQ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Activity at kappa opioid receptor expressed in HEK293 cells assessed as stimulation of [35S]GTPgammaS binding
Measurement: EC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 369.34, ALogP 4.4, HBA 2, HBD 0, PSA 23.55, QED 0.79
Compound (SMILES): CC[N+](CC)(CC(=O)Nc1c(C)cccc1C)Cc1ccccc1.O.O=C([O-])c1ccccc1
InChIKey: YYMVPVZYUYQSJE-UHFFFAOYSA-N
Target: Thyrotropin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P16473
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Agonists of the Thyroid Stimulating Hormone Receptor: Activators of Intracellular cAMP Concentrations in Parental HEK 293. (Class of assay: confirmatory) 
Measurement: Potency = 6309.6 nM (pChEMBL 5.199999809265137)
Descriptors: MW 325.48, ALogP 4.3, HBA 1, HBD 1, PSA 29.1, QED 0.76
Compound (SMILES): COc1ccc(-c2nnc3n2C[C@@H]2CCC[C@H]3N2C(=O)c2cccc(C(F)(F)F)c2Cl)nc1
InChIKey: RSXAXRWRVKMMQX-YVEFUNNKSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 477.87, ALogP 4.77, HBA 6, HBD 0, PSA 73.14, QED 0.54
Compound (SMILES): c1ccc2c(c1)nc(C1CCCN1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: PHNHVOBECABQNC-VSSIMEQCSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 ug membrane protein in a final volume of 500 uL 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 uL ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs. Fifty L/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count.
Measurement: Ki = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 446.68, ALogP 6.38, HBA 4, HBD 1, PSA 33.09, QED 0.59
Compound (SMILES): O=C(O)CN1CCC/C(=C2\N(CC(=O)O)c3ccccc3N2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: UHNUUYXYLQIOAI-LKOIZHRMSA-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 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 576.78, ALogP 5.53, HBA 6, HBD 2, PSA 87.56, QED 0.46
Compound (SMILES): COCCOCCOCCN1CCC[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: HOJZVJQPGCNNOD-TXBOPMPESA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 ug membrane protein in a final volume of 500 uL 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 uL ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs. Fifty L/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count.
Measurement: Ki = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 606.9, ALogP 6.81, HBA 7, HBD 0, PSA 51.99, QED 0.25
Compound (SMILES): c1ccc2c(c1)nc(Cc1nc[nH]n1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: JSCOEPOQLLRDLX-SSIAJPCRSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 ug membrane protein in a final volume of 500 uL 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 uL ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs. Fifty L/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count.
Measurement: Ki = 47.2 nM (pChEMBL 7.329999923706055)
Descriptors: MW 458.65, ALogP 5.66, HBA 5, HBD 1, PSA 62.63, QED 0.55
Compound (SMILES): COc1cnc(-c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@H]2C[C@@H]3CCCC[C@@H](C3)C2)cn1
InChIKey: NORRMTRHMDODPV-MRJPWHMWSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 ug membrane protein in a final volume of 500 uL 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 uL ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs. Fifty L/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count.
Measurement: Ki = 4.11 nM (pChEMBL 8.390000343322754)
Descriptors: MW 485.68, ALogP 6.42, HBA 6, HBD 0, PSA 56.07, QED 0.43
Compound (SMILES): c1ccc2c(c1)nc(-c1cnc[nH]1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCC[C@@H](C2)C1
InChIKey: BIQRROWUCAZDMH-WMXKIEPZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand binding assays were conducted using freshly thawed membranes expressing human mu-receptors (Perkin Elmer, Shelton, Conn.). Radioligand dose-displacement binding assays for human mu-opioid receptors used 0.2 nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20 mg membrane protein/well in a final volume of 500 uL 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 500 uL of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs.
Measurement: Ki = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 429.61, ALogP 5.95, HBA 4, HBD 1, PSA 49.74, QED 0.56
Compound (SMILES): c1ccc2c(c1)nc(-c1cc[nH]n1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCC[C@@H](C2)C1
InChIKey: PLQQMYPLKSUBJH-WMXKIEPZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand binding assays were conducted using freshly thawed membranes expressing human mu-receptors (Perkin Elmer, Shelton, Conn.). Radioligand dose-displacement binding assays for human mu-opioid receptors used 0.2 nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20 mg membrane protein/well in a final volume of 500 uL 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 500 uL of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs.
Measurement: Ki = 529 nM (pChEMBL 6.28000020980835)
Descriptors: MW 429.61, ALogP 5.95, HBA 4, HBD 1, PSA 49.74, QED 0.56
Compound (SMILES): Cn1cc(Cl)c(-c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCC[C@@H](C3)C2)n1
InChIKey: GKPUFILNQIRZKE-WMXKIEPZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand binding assays were conducted using freshly thawed membranes expressing human mu-receptors (Perkin Elmer, Shelton, Conn.). Radioligand dose-displacement binding assays for human mu-opioid receptors used 0.2 nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20 mg membrane protein/well in a final volume of 500 uL 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 500 uL of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs.
Measurement: Ki = 952 nM (pChEMBL 6.019999980926514)
Descriptors: MW 478.08, ALogP 6.62, HBA 5, HBD 0, PSA 38.88, QED 0.43
Compound (SMILES): Oc1cc(-c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCC[C@@H](C3)C2)nc(O)n1
InChIKey: IGFHLYPAGNSCQX-OBHIHTNZSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 ug membrane protein in a final volume of 500 uL 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 uL ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hrs. Fifty L/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count.
Measurement: Ki = 20.8 nM (pChEMBL 7.679999828338623)
Descriptors: MW 473.62, ALogP 5.43, HBA 7, HBD 2, PSA 87.3, QED 0.53
Compound (SMILES): CCN(CC)c1ccc(/C=N/NC(=O)CSc2nc3ccccc3o2)c(O)c1
InChIKey: XBEVTNMIQYQJLI-CIAFOILYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Binding affinity to RXRalpha-LBD (unknown origin) measured up to 300 sec by surface plasma resonance method
Measurement: Kd = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 398.49, ALogP 3.62, HBA 7, HBD 2, PSA 90.96, QED 0.34
Compound (SMILES): C[C@@H](C1CC1)N1CC[C@@]23CC(=O)CC[C@@]2(O)[C@H]1Cc1ccc(C(N)=O)c(O)c13
InChIKey: PEWWIMGLMQXNCF-ZKMDLRDOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: null: The Ki (binding affinity) for u opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human u opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 uM naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber.
Measurement: IC50 = 0.65 nM (pChEMBL 9.1899995803833)
Descriptors: MW 384.48, ALogP 1.64, HBA 5, HBD 3, PSA 103.86, QED 0.74
Compound (SMILES): O=C(NCCCOc1cccc([C@@](O)(C(=O)OCC2CCN(Cc3ccccc3)CC2)c2ccccc2)c1)c1ccc(CNCC(O)c2ccc(O)c3[nH]c(=O)ccc23)cc1
InChIKey: DGTRJTZMXLDJAT-WJCINHJDSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter
Measurement: Ki = 0.05012 nM (pChEMBL 10.300000190734863)
Descriptors: MW 824.98, ALogP 5.95, HBA 10, HBD 6, PSA 173.45, QED 0.04
Compound (SMILES): CN1CCC[C@@H](OC(=O)[C@](O)(c2ccccc2)c2cccc(OCCCNC(=O)c3cccc(CNC[C@H](O)c4ccc(O)c5[nH]c(=O)ccc45)c3)c2)C1
InChIKey: LHEDAJCFTHJHJR-WFRZLGIJSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 734.85, ALogP 4.13, HBA 10, HBD 6, PSA 173.45, QED 0.07
Compound (SMILES): COc1cc(C(=O)NCCCOc2cccc([C@](O)(C(=O)O[C@@H]3CCCN(C)C3)c3ccccc3)c2)c(OC)cc1CNC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12
InChIKey: PUJDPHOMQUAXSL-WPVDXGJHSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter
Measurement: Ki = 0.0631 nM (pChEMBL 10.199999809265137)
Descriptors: MW 794.9, ALogP 4.15, HBA 12, HBD 6, PSA 191.91, QED 0.06
Compound (SMILES): CN1CCC[C@@H](OC(=O)[C@](O)(c2ccccc2)c2cccc(OCCCNC(=O)c3ccc(CNC[C@H](O)c4ccc(O)c5[nH]c(=O)ccc45)c(F)c3)c2)C1.O=CO
InChIKey: QZWOLOIRKGCSJT-ZPOSWYPZSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter
Measurement: Ki = 0.01259 nM (pChEMBL 10.899999618530273)
Descriptors: MW 752.84, ALogP 4.27, HBA 10, HBD 6, PSA 173.45, QED 0.07
Compound (SMILES): O=C(c1ccc(CCNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)cc1)N1CCC(c2cccc([C@](O)(C(=O)OCC3CCN(Cc4ccccc4)CC3)c3ccccc3)c2)CC1
InChIKey: WKRZFUUGOIWNNT-HWPOXGSQSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter
Measurement: Ki = 0.3981 nM (pChEMBL 9.399999618530273)
Descriptors: MW 849.04, ALogP 6.81, HBA 9, HBD 5, PSA 155.43, QED 0.06
Compound (SMILES): COc1ccc(Nc2cc3c(cn2)n(C)c(=O)n3CC2CCN(C)CC2)c(C)c1
InChIKey: HVSWEYWJPNFCCN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha using PI(4,5)P2:PS as substrate in presence of ATP by ADP-Glo assay
Measurement: IC50 = 25300 nM (pChEMBL 4.599999904632568)
Descriptors: MW 395.51, ALogP 3.14, HBA 7, HBD 1, PSA 64.32, QED 0.72
Compound (SMILES): Cc1cc(CN2CCCCC2)cc(C)c1-c1ncn(C)c1-c1ccc2c(c1)OCC(=O)N2
InChIKey: VEWYIWGYIVHOBN-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96028
Assay: Binding affinity to human C-terminal his tagged NSD2 PWWP1 domain (208 to 358 residues) expressed in Escherichia coli Bl21 (DE3) gold cells assessed as dissociation constant measured upto 180 secs by SPR analysis
Measurement: Kd = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 430.55, ALogP 4.69, HBA 5, HBD 1, PSA 59.39, QED 0.65
Compound (SMILES): C[C@@H](COCCC(=O)NC1CCN(c2ncc(C(=O)NO)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: MPNZKBPNAZNHSB-LBPRGKRZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of full length C-terminal 6his-tagged human recombinant HDAC1 (1 to 482 residues) preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 528.49, ALogP 0.69, HBA 10, HBD 5, PSA 174.46, QED 0.17
Compound (SMILES): COc1ccc(S(=O)(=O)NCC(=O)Nc2ccc3c(=O)n4c(nc3c2)CCC4)c(OC)c1
InChIKey: NXKMOXOZHCNNDK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butyrylthiocholine iodide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 458.5, ALogP 1.28, HBA 8, HBD 2, PSA 128.62, QED 0.55
Compound (SMILES): CN1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3ccccn3)CC2)C[C@@H]1C1CCCC1
InChIKey: BXQJJJJXRPQHOA-IZZNHLLZSA-N
Target: Chitinase-3-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36222
Assay: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 453.07, ALogP 5.12, HBA 4, HBD 0, PSA 22.61, QED 0.63
Compound (SMILES): O=C1[C@H](c2ccccc2)[C@@H](c2ccccc2)N1C1CCN(C(=O)n2cncn2)CC1
InChIKey: GUHHGBPJTRBDRL-NHCUHLMSSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8R431
Assay: Inhibition of rat MAGL expressed in human HeLa cells using 2-arachidonoylglycerol as substrate preincubated with compound for 20 mins followed by substrate addition and measured after 30 mins by scintillation counting analysis
Measurement: IC50 = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 401.47, ALogP 3.08, HBA 5, HBD 0, PSA 71.33, QED 0.63
Compound (SMILES): N[C@@H](Cc1ccccc1)C(=O)NCCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: MAHWZMBJQNFHAJ-NRFANRHFSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE by microplate reader based analysis
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 402.54, ALogP 3.6, HBA 4, HBD 3, PSA 80.04, QED 0.5
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](CC(=O)O)NC(=O)S[C@@H](C(=O)O)NC(=O)[C@H]([C@H](C)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@H](C)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccc(O)cc2)NC1=O
InChIKey: CGYMRGTYHRRNMJ-CVLDGCJCSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Affinity Biochemical interaction: (Biolayer interferometry) EUB0002543a KDM4A
Measurement: Kd = 29.8 nM (pChEMBL 7.53000020980835)
Descriptors: MW 1996.15
Compound (SMILES): CO[C@@]12CC[C@@]3(CC1[C@](C)(O)CCc1cccs1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CCN1CC1CC1)C2O5
InChIKey: WTGSHWLSWVFVAH-KLJRBQEWSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for μ opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human μ opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 μM naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid.
Measurement: Ki = 0.43 nM (pChEMBL 9.369999885559082)
Descriptors: MW 521.72, ALogP 5.06, HBA 6, HBD 2, PSA 62.16, QED 0.53
Compound (SMILES): C[C@@H](C1CC1)N1CC[C@@]23CCCC[C@@H]2[C@H]1Cc1ccc(O)cc13
InChIKey: XLDNVUOEHMTAKQ-XVPDYNCKSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 M naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid. IC50 values were calculated by least squares fit to a logarithm-probit analysis. Ki values of unlabelled compounds were calculated from the equation Ki=(IC50)/1+S where S=(concentration of radioligand)/(Kd of radioligand) (Cheng and Prusoff, 1973).
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 311.47, ALogP 4.25, HBA 2, HBD 1, PSA 23.47, QED 0.88
Compound (SMILES): CO[C@@]12CC[C@@]3(C[C@@H]1[C@](C)(O)C(C)(C)C)[C@H]1Cc4ccc(C(N)=O)c5c4[C@@]3(CCN1CC1CC1)C2O5
InChIKey: PNSGSIISNKYAEX-LQNISFKASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for μ opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human μ opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 μM naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid.
Measurement: Ki = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 494.68, ALogP 3.81, HBA 5, HBD 2, PSA 85.02, QED 0.65
Compound (SMILES): CC(C)=CCN1CC[C@@]23CC(=O)CC[C@@]2(O)[C@H]1Cc1ccc(C(N)=O)c(O)c13
InChIKey: APTNTDOSAMTDKL-VOQZNFBZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 M naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid. IC50 values were calculated by least squares fit to a logarithm-probit analysis. Ki values of unlabelled compounds were calculated from the equation Ki=(IC50)/1+S where S=(concentration of radioligand)/(Kd of radioligand) (Cheng and Prusoff, 1973).
Measurement: EC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 384.48, ALogP 1.81, HBA 5, HBD 3, PSA 103.86, QED 0.69
Compound (SMILES): C=C1CC[C@@]2(O)[C@H]3Cc4ccc(C(N)=O)c(O)c4[C@]2(CCN3CC=C(C)C)C1
InChIKey: NMTVXFMUGDYYGM-YFXJRYMSSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 M naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid. IC50 values were calculated by least squares fit to a logarithm-probit analysis. Ki values of unlabelled compounds were calculated from the equation Ki=(IC50)/1+S where S=(concentration of radioligand)/(Kd of radioligand) (Cheng and Prusoff, 1973).
Measurement: EC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 382.5, ALogP 2.8, HBA 4, HBD 3, PSA 86.79, QED 0.7
Compound (SMILES): C[C@H](C1CC1)N1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(C(N)=O)cc13
InChIKey: WKSWYCJGHDWJFK-XKWBKWALSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 M naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid. IC50 values were calculated by least squares fit to a logarithm-probit analysis. Ki values of unlabelled compounds were calculated from the equation Ki=(IC50)/1+S where S=(concentration of radioligand)/(Kd of radioligand) (Cheng and Prusoff, 1973).
Measurement: EC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 338.5, ALogP 3.64, HBA 2, HBD 1, PSA 46.33, QED 0.91
Compound (SMILES): C[C@H](C1CC1)N1CC[C@@]23CC(=O)CC[C@@]2(O)[C@H]1Cc1ccc(C(N)=O)c(O)c13
InChIKey: PEWWIMGLMQXNCF-RCLMMODESA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 M naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid. IC50 values were calculated by least squares fit to a logarithm-probit analysis. Ki values of unlabelled compounds were calculated from the equation Ki=(IC50)/1+S where S=(concentration of radioligand)/(Kd of radioligand) (Cheng and Prusoff, 1973).
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 384.48, ALogP 1.64, HBA 5, HBD 3, PSA 103.86, QED 0.74
Compound (SMILES): C[C@H](C1CCC1)N1CC[C@@]23CC(=O)CC[C@@]2(O)[C@H]1Cc1ccc(C(N)=O)c(O)c13
InChIKey: JWIGXHPEGWQVAB-ANKAOXSHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Opioid Receptor Binding Assay: The Ki (binding affinity) for opioid receptors was determined using a competitive displacement assay as previously described in Neumeyer (Journal of Med. Chem. 2012, p 3878), which is incorporated herein in its entirety. Briefly, membrane protein from CHO (Chinese Hamster Ovarian) cells that stably expressed the cloned human opioid receptor were incubated with 12 different concentrations of the compound set forth herein in the presence of 0.25 nM [3H]DAMGO (see Tiberi et al., Can. J. Physiol. Pharmacol. 1988, Vol. 66, p 1368, which is incorporated by reference herein in its entirety) in a final volume of 1 mL of 50 mM Tris-HCl, pH 7.5 at 25° C. Incubation times of 60 min were used for [3H]DAMGO (see Gulati et al., Life Sci. 1990, Vol. 47, p 159, which is incorporated by reference herein in its entirety). Nonspecific binding was measured by inclusion of 10 M naloxone. The binding was terminated by filtering the samples through Schleicher & Schuell No. 32 glass fiber filters using a Brandel 48-well cell harvester. The filters were subsequently washed three times with 3 mL of cold 50 mM Tris-HCl, pH 7.5, and were counted in 2 mL Ecoscint A scintillation fluid. IC50 values were calculated by least squares fit to a logarithm-probit analysis. Ki values of unlabelled compounds were calculated from the equation Ki=(IC50)/1+S where S=(concentration of radioligand)/(Kd of radioligand) (Cheng and Prusoff, 1973).
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 398.5, ALogP 2.03, HBA 5, HBD 3, PSA 103.86, QED 0.72
Compound (SMILES): COc1ccc(-c2nnc3n2C[C@H]2CCC[C@@H]3N2C(=O)c2cccc(C(F)(F)F)c2Cl)nc1
InChIKey: RSXAXRWRVKMMQX-PXAZEXFGSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Ca2+ Flux Assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)).
Measurement: IC50 = 1906 nM (pChEMBL 5.71999979019165)
Descriptors: MW 477.87, ALogP 4.77, HBA 6, HBD 0, PSA 73.14, QED 0.54