lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CS(=O)(=O)NCCN1CC[C@@H](Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: CNIZVMPOGMXZSM-MVQHYNIRSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro ORL-1 Receptor Binding Assay: ORL-1 Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at −80° C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. The data from screening and dose-displacement experiments were analyzed using Microsoft Excel and the curve fitting functions in GraphPad PRISM¿, v. 3.0, respectively, or an in-house function for one-site competition curve-fitting.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 581.87, ALogP 5.37, HBA 6, HBD 1, PSA 70.47, QED 0.45
Compound (SMILES): CCN(CC)C(=O)CN1CCC[C@@H](Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: ITKASYXFOFGZNO-CCMYSEMPSA-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 = 47.9 nM (pChEMBL 7.320000171661377)
Descriptors: MW 587.9, ALogP 7.08, HBA 5, HBD 0, PSA 44.61, QED 0.33
Compound (SMILES): CCN(CC)C(=O)CN1CC[C@@H](Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)C1
InChIKey: RMSTWPKEPDMVNK-QXGXYANZSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro ORL-1 Receptor Binding Assay: ORL-1 Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at −80° C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. The data from screening and dose-displacement experiments were analyzed using Microsoft Excel and the curve fitting functions in GraphPad PRISM¿, v. 3.0, respectively, or an in-house function for one-site competition curve-fitting.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 573.87, ALogP 6.69, HBA 5, HBD 0, PSA 44.61, QED 0.35
Compound (SMILES): OC1=N[C@H](Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)CC1
InChIKey: OFOHXKVALJQEPL-SUJRTSPLSA-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 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 474.69, ALogP 6.61, HBA 4, HBD 1, PSA 53.65, QED 0.54
Compound (SMILES): c1ccc2c(c1)nc(C[C@H]1COCCN1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: ZFJWLWOSYSURLC-XMVZRQGPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro ORL-1 Receptor Binding Assay: ORL-1 Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at −80° C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. The data from screening and dose-displacement experiments were analyzed using Microsoft Excel and the curve fitting functions in GraphPad PRISM¿, v. 3.0, respectively, or an in-house function for one-site competition curve-fitting.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 476.71, ALogP 5.48, HBA 5, HBD 1, PSA 42.32, QED 0.63
Compound (SMILES): c1ccc2c(c1)nc(C[C@@H]1COCCN1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: ZFJWLWOSYSURLC-VIQQYPKZSA-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 = 1669 nM (pChEMBL 5.78000020980835)
Descriptors: MW 476.71, ALogP 5.48, HBA 5, HBD 1, PSA 42.32, QED 0.63
Compound (SMILES): Cn1ccnc1CN1CCOC[C@H]1Cc1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: KNVZCDCWXGRYIU-QIPLTTJJSA-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 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 570.83, ALogP 6.13, HBA 7, HBD 0, PSA 51.35, QED 0.36
Compound (SMILES): O=C(O)CCN1CCC[C@H]1Cc1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: HCRKFMPEDIKLJD-WCSHMYRTSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro ORL-1 Receptor Binding Assay: ORL-1 Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at −80° C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. The data from screening and dose-displacement experiments were analyzed using Microsoft Excel and the curve fitting functions in GraphPad PRISM¿, v. 3.0, respectively, or an in-house function for one-site competition curve-fitting.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 532.77, ALogP 6.43, HBA 5, HBD 1, PSA 61.6, QED 0.44
Compound (SMILES): O=C(O)CN1CCCC[C@H]1Cc1nc2ccccc2n1[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: DSWUBPMMBDNJSP-WCSHMYRTSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro ORL-1 Receptor Binding Assay: ORL-1 Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at −80° C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hrs. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. The data from screening and dose-displacement experiments were analyzed using Microsoft Excel and the curve fitting functions in GraphPad PRISM¿, v. 3.0, respectively, or an in-house function for one-site competition curve-fitting.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 532.77, ALogP 6.43, HBA 5, HBD 1, PSA 61.6, QED 0.46
Compound (SMILES): c1ccc2c(c1)nc(Cc1cnccn1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@@H]1C[C@@H]2CCCC[C@@H](C2)C1
InChIKey: BGPVEBATJGVAJE-KEQUZKIMSA-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 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 469.68, ALogP 6.33, HBA 5, HBD 0, PSA 46.84, QED 0.45
Compound (SMILES): Cc1nc(Cc2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@@H]2C[C@@H]3CCCC[C@@H](C3)C2)n[nH]1
InChIKey: JRRQXSDUQMJLBB-ZWZZYCPGSA-N
Target: 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 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 472.68, ALogP 5.97, HBA 5, HBD 1, PSA 62.63, QED 0.51
Compound (SMILES): c1ccc2c(c1)nc(-c1cnccn1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@H]1C[C@@H]2CCC[C@@H](C2)C1
InChIKey: WAXPTENBBCNPBM-JYWISYRRSA-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 = 21.6 nM (pChEMBL 7.670000076293945)
Descriptors: MW 441.62, ALogP 6.02, HBA 5, HBD 0, PSA 46.84, QED 0.5
Compound (SMILES): Cc1nc(C)c(-c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@H]2C[C@@H]3CCC[C@@H](C3)C2)s1
InChIKey: JELMLDMWPYFDOT-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 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 474.72, ALogP 7.3, HBA 5, HBD 0, PSA 33.95, QED 0.4
Compound (SMILES): c1ccc2c(c1)nc(-c1ccno1)n2[C@H]1C[C@H]2CCC[C@@H](C1)N2[C@H]1C[C@@H]2CCC[C@@H](C2)C1
InChIKey: VCYFDNASPXMJOM-FGGOGHJKSA-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 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 430.6, ALogP 6.22, HBA 5, HBD 0, PSA 47.09, QED 0.49
Compound (SMILES): Cc1cc(-c2nc3ccccc3n2[C@H]2C[C@H]3CCC[C@@H](C2)N3[C@H]2C[C@@H]3CCC[C@@H](C3)C2)no1
InChIKey: HRBNMCQBXRYPRZ-JYWISYRRSA-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 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 444.62, ALogP 6.53, HBA 5, HBD 0, PSA 47.09, QED 0.46
Compound (SMILES): Cc1cccc(-n2nccc2-c2cc3cnccc3s2)n1
InChIKey: NTOWMPDTXYCCPD-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 292.37, ALogP 3.85, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): Cc1cccc(-n2nc(C)cc2-c2cc3cnccc3s2)n1
InChIKey: JNXNNFRGVXEOSW-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 306.39, ALogP 4.16, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): CCc1cc(-c2cc3cnccc3s2)n(-c2cccc(C)n2)n1
InChIKey: MHHYZOIPYYNHIX-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 403 nM (pChEMBL 6.389999866485596)
Descriptors: MW 320.42, ALogP 4.41, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): CCc1cnn(-c2cccc(C)n2)c1-c1cc2cnccc2s1
InChIKey: NIQVUPWBHUGPKD-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 21.5 nM (pChEMBL 7.670000076293945)
Descriptors: MW 320.42, ALogP 4.41, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): Cc1cccc(-n2nc3c(c2-c2cc4cnccc4s2)CCC3)n1
InChIKey: JQKNNVYRFRWQST-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 30.8 nM (pChEMBL 7.510000228881836)
Descriptors: MW 332.43, ALogP 4.34, HBA 5, HBD 0, PSA 43.6, QED 0.55
Compound (SMILES): Cc1cccc(-n2nc(C)c(C)c2-c2cc3cnccc3s2)n1
InChIKey: TVXWXMHIKISOHR-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 244 nM (pChEMBL 6.610000133514404)
Descriptors: MW 320.42, ALogP 4.47, HBA 5, HBD 0, PSA 43.6, QED 0.55
Compound (SMILES): Cc1cccc(-n2ncc(C)c2-c2cc3cnccc3s2)n1
InChIKey: VRQZQTWWFHBPNK-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 35.9 nM (pChEMBL 7.449999809265137)
Descriptors: MW 306.39, ALogP 4.16, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): Cc1cccc(-n2ncc(C)c2-c2cc3ccncc3s2)n1
InChIKey: QLZNPZBCUHGMCT-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 42.5 nM (pChEMBL 7.369999885559082)
Descriptors: MW 306.39, ALogP 4.16, HBA 5, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): Cc1cccc(-n2nc3c(c2-c2cc4ccncc4s2)CCC3)n1
InChIKey: UVJODQMWHIJIMO-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: ALK-5 Gene : ALK-5 gene reporter assay methods have been described in the art (see e.g., Maliekal et al. (2004) J Biol Chem 279(35):36287-36292). The compounds named in the specified Examples were tested as follows for inhibition of Smad binding element (SBE) luciferase reporter activity in TGFbeta1 stimulated NIH-3T3 cells. The following luciferase assay employs NIH/3T3 (murine fibroblast) cells, which are transiently transfected with a Smad binding element (SBE) luciferase reporter construct. This expressed construct is responsive to agents that stimulate the Smad signaling pathway.
Measurement: IC50 = 57.5 nM (pChEMBL 7.239999771118164)
Descriptors: MW 332.43, ALogP 4.34, HBA 5, HBD 0, PSA 43.6, QED 0.55
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cnc(N4CCCC4C4CCCCN4C)cc2OCC3)n(CC(F)(F)F)n1
InChIKey: BTRBVLVZBYMHDD-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.107 nM (pChEMBL 9.970000267028809)
Descriptors: MW 516.57, ALogP 3.92, HBA 9, HBD 0, PSA 77.13, QED 0.52
Compound (SMILES): CC(C)n1ncnc1-c1cn2c(n1)-c1cc(CN3CCN(C(C)(C)C)CC3)ccc1OCC2
InChIKey: MBNYACZBQVCQMH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 449.6, ALogP 3.7, HBA 8, HBD 0, PSA 64.24, QED 0.61
Compound (SMILES): CC(C)n1ncnc1-c1cn2c(n1)-c1cc(C(=O)N3CCN(C(C)(C)C)CC3)ccc1OCC2
InChIKey: ORAFSXNAIORUHG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 463.59, ALogP 3.34, HBA 8, HBD 0, PSA 81.31, QED 0.59
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CCCN(C(C)(C)CO)C4)cc2OCC3)n(C(C)C)n1
InChIKey: MANLYGWZZVOIHV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.485 nM (pChEMBL 9.3100004196167)
Descriptors: MW 544.7, ALogP 4.44, HBA 10, HBD 1, PSA 99.05, QED 0.38
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4ccnn4C4CCCN(C(C)(C)CO)C4)cc2OCC3)n(C(C)C)n1
InChIKey: XPPGOMOXJOINTN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.292 nM (pChEMBL 9.539999961853027)
Descriptors: MW 530.68, ALogP 4.36, HBA 10, HBD 1, PSA 99.05, QED 0.4
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC4C4CCN(CC(C)(C)O)CC4)cc2OCC3)n(C(C)C)n1
InChIKey: KKGAZYXSQJZBNU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 533.72, ALogP 4.54, HBA 9, HBD 1, PSA 84.47, QED 0.5
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CCCN(C(C)C)C4)cc2OCC3)n(C(C)C)n1
InChIKey: KIYKQIDKJXPBAJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.494 nM (pChEMBL 9.3100004196167)
Descriptors: MW 514.68, ALogP 5.08, HBA 9, HBD 0, PSA 78.82, QED 0.37
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCC4C4CCN(C)CC4)cc2OCC3)n(C(C)C)n1
InChIKey: HJZZIFQOTCGMQP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.708 nM (pChEMBL 9.149999618530273)
Descriptors: MW 461.61, ALogP 4.01, HBA 8, HBD 0, PSA 64.24, QED 0.59
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@@H](C)N4CCN(C(C)(C)C)CC4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: XLJFYTCFZPOLIV-GOSISDBHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 495.65, ALogP 4.71, HBA 8, HBD 0, PSA 64.24, QED 0.52
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CC(N(C)C)CCO4)cc2OCC3)n(C(C)C)n1
InChIKey: AYZRGQPKPDHNAX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 1.65 nM (pChEMBL 8.779999732971191)
Descriptors: MW 516.65, ALogP 4.27, HBA 10, HBD 0, PSA 88.05, QED 0.39
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@H](C)N4CCN(C(C)(C)C)CC4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: XLJFYTCFZPOLIV-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 495.65, ALogP 4.71, HBA 8, HBD 0, PSA 64.24, QED 0.52
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@@H](C)N4CCN(C(C)(C)C)CC4)c(C)cc2OCC3)n(C(C)C)n1
InChIKey: ROEMKOMVFBZVIY-HXUWFJFHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 491.68, ALogP 4.88, HBA 8, HBD 0, PSA 64.24, QED 0.52
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@H](C)N4CCN(C(C)(C)C)CC4)c(C)cc2OCC3)n(C(C)C)n1
InChIKey: ROEMKOMVFBZVIY-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 0.88 nM (pChEMBL 9.0600004196167)
Descriptors: MW 491.68, ALogP 4.88, HBA 8, HBD 0, PSA 64.24, QED 0.52
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@H](C)N4CCN(C(C)(C)C)CC4)ncc2OCC3)n(C(C)C)n1
InChIKey: DKDCWBXTCFPFMR-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 478.65, ALogP 3.96, HBA 9, HBD 0, PSA 77.13, QED 0.56
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc([C@@H](C)N4CCN(C(C)(C)C)CC4)ncc2OCC3)n(C(C)C)n1
InChIKey: DKDCWBXTCFPFMR-GOSISDBHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to PI3Kdelta (unknown origin)
Measurement: Ki = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 478.65, ALogP 3.96, HBA 9, HBD 0, PSA 77.13, QED 0.56
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC4C4CCCN(C)C4)cc2OCC3)n(C(C)C)n1
InChIKey: XUSKNOLOZFGDSE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 2.81 nM (pChEMBL 8.550000190734863)
Descriptors: MW 475.64, ALogP 4.4, HBA 8, HBD 0, PSA 64.24, QED 0.56
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC45CCCN(C)C5)cc2OCC3)n(C(C)C)n1
InChIKey: BEPHFNMMVHDLQJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.178 nM (pChEMBL 9.75)
Descriptors: MW 461.61, ALogP 4.15, HBA 8, HBD 0, PSA 64.24, QED 0.58