lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C(=O)Cc1ccc(Cl)c(Cl)c1)C1CCCCC1N1CCCC1.Cl
InChIKey: KGMMGVIYOHGOKQ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Agonist activity at mouse kappa opioid receptor-1 expressed in CHO cell membranes assessed as [35S]GTPgammaS binding incubated for 60 mins by scintillation spectroscopic analysis
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 369.34, ALogP 4.4, HBA 2, HBD 0, PSA 23.55, QED 0.79
Compound (SMILES): CN(C(=O)Cc1ccc(Cl)c(Cl)c1)C1CCCCC1N1CCCC1.O=C(O)[C@H](O)[C@@H](O)C(=O)O
InChIKey: DMBKHRMAGYYBJM-LREBCSMRSA-N
Target: Beta-lactamase (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P00811
Assay: PUBCHEM_BIOASSAY: qHTS Inhibitors of AmpC Beta-Lactamase (assay with detergent). (Class of assay: confirmatory) [Related pubchem assays: 1002 (Confirmation Concentration-Response Assay for Inhibitors of AmpC Beta-Lactamase (assay with detergent)), 585 (Promiscuous and Specific Inhibitors of AmpC Beta-Lactamase (assay without detergent) - a screen old NIH MLSMR collection), 584 (Promiscuous and Specific Inhibitors of AmpC Beta-Lactamase (assay with detergent) - a screen of the old NIH MLSMR collection), 1003 (Confirmation Cuvette-Based Assay for Inhibitors of AmpC Beta-Lactamase (assay with detergent))]
Measurement: Potency = 5011.9 nM (pChEMBL 5.300000190734863)
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: Prelamin-A/C (SINGLE PROTEIN), Homo sapiens
UniProt: P02545
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Modulators of Lamin A Splicing. (Class of assay: confirmatory) 
Measurement: Potency = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 325.48, ALogP 4.3, HBA 1, HBD 1, PSA 29.1, QED 0.76
Compound (SMILES): COc1cc2c(cc1O)CN1CC[C@@]23C=CC(O)C[C@H]13
InChIKey: TZTBAJFJEZRQCV-BPWRPNSKSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine as substrate assessed as concentration of 5-thio-2-nitrobenzoic acid ion formed by spectrophotometric/Ellman's method
Measurement: IC50 = 57400 nM (pChEMBL 4.239999771118164)
Descriptors: MW 273.33, ALogP 1.55, HBA 4, HBD 2, PSA 52.93, 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), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 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.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: In Vitro Delta-Opioid Receptor Binding Assay: δ-Opioid Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: In Vitro Delta-Opioid Receptor Binding Assay: δ-Opioid Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 21.7 nM (pChEMBL 7.659999847412109)
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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: In Vitro Delta-Opioid Receptor Binding Assay: δ-Opioid Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: In Vitro Delta-Opioid Receptor Binding Assay: δ-Opioid Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: In Vitro Delta-Opioid Receptor Binding Assay: δ-Opioid Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 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: 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 = 6 nM (pChEMBL 8.220000267028809)
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: 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 = 4.9 nM (pChEMBL 8.3100004196167)
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: 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 = 6.7 nM (pChEMBL 8.170000076293945)
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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: In Vitro Delta-Opioid Receptor Binding Assay: δ-Opioid Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hrs. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 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: Antagonist activity at RXRalpha (unknown origin) expressed in HEK293T cells assessed as inhibition of receptor transactivation after 12 hrs in presence of 9-cis-RA by luciferase reporter gene assay
Measurement: IC50 = 2810 nM (pChEMBL 5.550000190734863)
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: Ki = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 384.48, ALogP 1.64, HBA 5, HBD 3, PSA 103.86, QED 0.74
Compound (SMILES): O=C(O[C@@H]1C[N+]2(CCCCc3ccccc3)CCC1CC2)C(O)(c1cccs1)c1cccs1
InChIKey: TWCNWISPABVKII-TUSHJWFTSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: [3H]-NMS Binding Assay: The binding of [3H]-NMS to human muscarinic receptors was performed according to Waelbroek et al (1990) (1). Assays were carried out at 25° C. Membrane preparations from stably transfected chinese hamster ovary-K1 cells (CHO) expressing the genes for the human muscarinic receptors Hm3 were used.
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 482.69, ALogP 5.22, HBA 5, HBD 1, PSA 46.53, QED 0.26
Compound (SMILES): Cc1ncccc1-c1cc2c(n3cnnc13)NCc1c(F)ccc3c1[C@H](CO3)CO2
InChIKey: JQBUTSBIFNKJMW-CYBMUJFWSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: Binding affinity to EED (unknown origin) assessed as dissociation constant
Measurement: Kd = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 403.42, ALogP 3.72, HBA 7, HBD 1, PSA 73.57, QED 0.52
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: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter
Measurement: Ki = 10 nM (pChEMBL 8)
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: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter
Measurement: Ki = 0.3981 nM (pChEMBL 9.399999618530273)
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: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter
Measurement: Ki = 0.3162 nM (pChEMBL 9.5)
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: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter
Measurement: Ki = 0.7943 nM (pChEMBL 9.100000381469727)
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: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter
Measurement: Ki = 0.0631 nM (pChEMBL 10.199999809265137)
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: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of human DNA-PK using EPPLSQEAFADLWK as substrate in presence of ATP by kinase hotspot assay
Measurement: IC50 > 100 nM (pChEMBL 7)
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: Inhibition of human C-terminal his tagged NSD2 PWWP1 domain (208 to 358 residues) expressed in Escherichia coli Bl21 (DE3) gold cells incubated for 45 mins by biochemical assay
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 430.55, ALogP 4.69, HBA 5, HBD 1, PSA 59.39, QED 0.65
Compound (SMILES): Cc1ccc(CO)cc1-c1ncn(C)c1-c1ccc2c(c1)OCC(=O)N2
InChIKey: GFIQDMKDUFQAHX-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96028
Assay: Inhibition of human C-terminal his tagged NSD2 PWWP1 domain (208 to 358 residues) expressed in Escherichia coli Bl21 (DE3) gold cells incubated for 45 mins by biochemical assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 349.39, ALogP 2.89, HBA 5, HBD 2, PSA 76.38, QED 0.76
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: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Inhibition of N-terminal FLAG tagged human PARP7 (400 to 657 residues) preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 528.49, ALogP 0.69, HBA 10, HBD 5, PSA 174.46, QED 0.17
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)N)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O
InChIKey: JHPLDUFKMYOICI-HIQIDBLNSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at human FPR2 expressed in HL-60 cells assessed as inhibition of WKYMVM-induced calcium mobilization
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 2320.82
Compound (SMILES): COc1ccc(S(=O)(=O)NCC(=O)Nc2ccc3c(=O)n4c(nc3c2)CCC4)c(OC)c1
InChIKey: NXKMOXOZHCNNDK-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine 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 = 9190 nM (pChEMBL 5.039999961853027)
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 ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay
Measurement: IC50 = 194 nM (pChEMBL 6.710000038146973)
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), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL (1 to 303 residues) expressed in human HeLa cells using 2-arachidonoylglycerol as substrate preincubated with compound for 20 mins followed by substrate addition and measured after 20 mins by scintillation counting analysis
Measurement: IC50 = 11.51 nM (pChEMBL 7.940000057220459)
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: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE by microplate reader based analysis
Measurement: IC50 = 239 nM (pChEMBL 6.619999885559082)
Descriptors: MW 402.54, ALogP 3.6, HBA 4, HBD 3, PSA 80.04, QED 0.5
Compound (SMILES): O=C1NC(=O)/C(=C/c2ccc(OCCNc3nc4c(cnn4C4CCCC4)c(=O)[nH]3)c(F)c2)S1
InChIKey: BQRJSNGPMNBZKA-YVLHZVERSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of PDE9A (unknown origin)
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 484.51, ALogP 3.19, HBA 9, HBD 3, PSA 131, QED 0.34
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: (AlphaScreen) EUB0002543a KDM4A
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
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: IC50 = 0.28 nM (pChEMBL 9.550000190734863)
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: Ki = 18 nM (pChEMBL 7.75)
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: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
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: Ki = 0.56 nM (pChEMBL 9.25)
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: Ki = 0.5 nM (pChEMBL 9.300000190734863)
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: Ki = 0.083 nM (pChEMBL 10.079999923706055)
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: Ki = 5.8 nM (pChEMBL 8.239999771118164)
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: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 398.5, ALogP 2.03, HBA 5, HBD 3, PSA 103.86, QED 0.72
Compound (SMILES): O=C(O[C@H]1C[N+]2(CCCc3cccs3)CCC1CC2)C1(O)C2C=CC=CC2C2C=CC=CC21
InChIKey: CNJZRYJQSFDHSO-SQWRETMTSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: [3H]-NMS Binding Assay: Assays were carried out at 25° C. Membrane preparations from stably transfected chinese hamster ovary-K1 cells (CHO) expressing the genes for the human muscarinic receptors Hm3 were used. For determination of IC, membrane preparations were suspended in DPBS to a final concentration of 89 μg/ml for the Hm3 subtype. The membrane suspension was incubated with the tritiated compound for 60 min. After incubation the membrane fraction was separated by filtration and the bound radioactivity determined. Non specific binding was determined by addition of 10^−4 M atropine. At least six concentrations were assayed in duplicate to generate individual displacement curves.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 464.65, ALogP 4.29, HBA 4, HBD 1, PSA 46.53, QED 0.5
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: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 477.87, ALogP 4.77, HBA 6, HBD 0, PSA 73.14, QED 0.54
Compound (SMILES): Cc1cc(Nc2cc3ncccc3c(N[C@@H]3C[C@H]4CCC[C@@](C)(C3)N4C(=O)c3ccc(C#N)nc3)n2)n[nH]1
InChIKey: FMEUWZNHLJAMGP-CJYOKPGZSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Biochemical JAK Assay: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies.Serially diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for lh. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for lh before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.Test compounds having a higher pKi value in each of the four JAK assays show greater inhibition of JAK activity. Compounds of the invention tested in this assay typically exhibited pKi values between about 7 and about 10.3
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 507.6, ALogP 4.7, HBA 8, HBD 3, PSA 135.51, QED 0.35
Compound (SMILES): COc1cc(Nc2cc(CO)[nH]n2)nc(N[C@@H]2C[C@H]3CCC[C@@H](C2)N3S(=O)(=O)C2CC(C#N)C2)n1
InChIKey: XTYCAGFJNDEYTK-ODXPNFLKSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Biochemical JAK Kinase Assay: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies.Serially diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for 1 h. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for 1 h before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.
Measurement: Ki < 0.1 nM (pChEMBL 10)
Descriptors: MW 502.6, ALogP 1.87, HBA 10, HBD 4, PSA 169.15, QED 0.42