lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(CN(C)C(=O)c2cccc(C(=O)N[C@@H](Cc3ccccc3)[C@H](O)C3NCCN(Cc4ccccc4)C3=O)c2)cs1
InChIKey: JCNCCHUDAASMSY-GAVYTZHXSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: The potencies of compounds were determined by measurement of their inhibition of memapsin 2 catalytic activity toward a fluorescent substrate. Kinetic inhibition experiments were performed using the procedure as described in Ermolieff, et al. Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety. Briefly, assays were performed at pH 4, 37° C., by pre-incubation of memapsin 2 enzyme with compound for 20 minutes. Activity measure was initiated by addition of a fluorogenic substrate FS-2 (Bachem Americas, Torrance, Calif.).
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 611.77, ALogP 3.43, HBA 7, HBD 3, PSA 114.87, QED 0.24
Compound (SMILES): CC(=O)CCCOc1nc(Oc2ccc3c(c2)COB3O)cc(C(F)(F)F)c1C#N
InChIKey: NSVZCMUAFBWPEB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 420.15
Compound (SMILES): Cc1cc(Oc2nc(OCCOC(C)C)c(C#N)cc2Cl)cc2c1B(O)OC2
InChIKey: XQZSDSGBZZUHKR-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 402.64
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: PKOKZOVQUJMMJL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 338.8, ALogP 4.38, HBA 5, HBD 2, PSA 59.07, QED 0.64
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: HOLZGQKSANGENU-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 = 1530 nM (pChEMBL 5.820000171661377)
Descriptors: MW 352.83, ALogP 4.42, HBA 5, HBD 2, PSA 59.07, QED 0.63
Compound (SMILES): O=S1(=O)Nc2cccc(c2)CNc2nc(ncc2Cl)Nc2cccc1c2
InChIKey: ARCKFUMURBKDRR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 387.85, ALogP 3.6, HBA 6, HBD 3, PSA 96.01, QED 0.55
Compound (SMILES): O=C1Nc2cccc(c2)CNc2nc(ncc2Cl)Nc2cccc1c2
InChIKey: WKFDYXPIKYJBDD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 351.8, ALogP 4.05, HBA 5, HBD 3, PSA 78.94, QED 0.57
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCCc1cccc(c1)N2
InChIKey: WILMKMPUMOSDLH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 366.85, ALogP 4.81, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): C[C@H]1Nc2nc(ncc2Cl)Nc2cccc(c2)COc2cccc1c2
InChIKey: OMIMDZMFZXMMGS-GFCCVEGCSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 352.83, ALogP 4.94, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCOc1cccc(c1)N2
InChIKey: JRMWFZSAQXNBSZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 368.82, ALogP 4.26, HBA 6, HBD 2, PSA 68.3, QED 0.62
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: BBVOVZFYMUEXGT-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.83, ALogP 4.42, HBA 5, HBD 2, PSA 59.07, QED 0.63
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: DDEPHNOBUQYIBZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 366.85, ALogP 4.46, HBA 5, HBD 2, PSA 59.07, QED 0.61
Compound (SMILES): Clc1cnc2nc1NCCCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: PGBXYNXDKMTLPH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 366.85, ALogP 4.81, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): C[C@@H]1Nc2nc(ncc2Cl)Nc2cccc(c2)COc2cccc1c2
InChIKey: OMIMDZMFZXMMGS-LBPRGKRZSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 352.83, ALogP 4.94, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCCCc1cccc(c1)N2
InChIKey: YCEQOGSAKUVGII-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 380.88, ALogP 4.85, HBA 5, HBD 2, PSA 59.07, QED 0.58
Compound (SMILES): Clc1cnc2nc1NCCCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: NLGCDKKLEZPXLI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 380.88, ALogP 4.85, HBA 5, HBD 2, PSA 59.07, QED 0.58
Compound (SMILES): Clc1cnc2nc1NCc1cc(ccc1Br)OCCCc1cccc(c1)N2
InChIKey: YYZSNJQQGCXQNG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 445.75, ALogP 5.57, HBA 5, HBD 2, PSA 59.07, QED 0.47
Compound (SMILES): Clc1cnc2nc1NCc1cc(ccc1-c1ccccc1)OCCCc1cccc(c1)N2
InChIKey: JHMLRNFFLKYFAU-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 442.95, ALogP 6.48, HBA 5, HBD 2, PSA 59.07, QED 0.35
Compound (SMILES): Clc1cnc2nc1NCc1cc(Br)cc(c1)OCCCc1cccc(c1)N2
InChIKey: IBAVCNVUPMTBKJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 445.75, ALogP 5.57, HBA 5, HBD 2, PSA 59.07, QED 0.47
Compound (SMILES): Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)NC2
InChIKey: FKLWUWJYBORMDH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 352.83, ALogP 3.56, HBA 6, HBD 3, PSA 88.75, QED 0.54
Compound (SMILES): O=C(Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)NC2)c1ccccc1
InChIKey: DZOSAHMEHFLHAZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.94, ALogP 5.23, HBA 6, HBD 3, PSA 91.83, QED 0.38
Compound (SMILES): N#Cc1ccccc1S(=O)(=O)Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)NC2
InChIKey: AVINPMJXOWDOIE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518, ALogP 4.65, HBA 8, HBD 3, PSA 132.69, QED 0.36
Compound (SMILES): CC1CCN(c2nc(C(F)(F)F)ccc2CNC(=O)Nc2ccc(CNS(C)(=O)=O)c(F)c2)CC1
InChIKey: NAXMRUCVDLYTPD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The FLIPR protocol consists of 2 substance additions. First the compounds to be tested (10 μM) are pipetted onto the cells and the Ca2+ influx is compared with the control (capsaicin 10 μM). This provides the result in % activation based on the Ca2+ signal after the addition of 10 μM of capsaicin (CP). After 5 minutes incubation, 100 nM of capsaicin are applied and the Ca2+ influx is also determined. Desensitising agonists and antagonists lead to suppression of the Ca2+ influx. The % inhibition is calculated compared to the maximum achievable inhibition with 10 μM of capsazepine. Starting from the percentage displacement caused by different concentrations of the compounds to be tested of general formula I, IC50 inhibitory concentrations which cause a 50-percent displacement of capsaicin were calculated. K1 values for the test substances were obtained by conversion by means of the Cheng-Prusoff equation (Cheng, Prusoff; Biochem. Pharmacol. 22, 3099-3108, 1973).
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 517.55, ALogP 3.85, HBA 5, HBD 3, PSA 103.43, QED 0.48
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4nnc(NC5CC5)s4)ccn23)c1
InChIKey: IBSMXTBTUWUZJT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 473.48, ALogP 4.78, HBA 7, HBD 3, PSA 96.24, QED 0.37
Compound (SMILES): Cn1ccnc1C#Cc1ccn2c(-c3cccc(NC(=O)NCC(F)(F)F)c3)cnc2c1
InChIKey: VDVHTIUPAJLKPX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 438.41, ALogP 3.82, HBA 5, HBD 2, PSA 76.25, QED 0.48
Compound (SMILES): COCc1cc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)nc(N)n1
InChIKey: UNDXJKNUAVWPOA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 471.44, ALogP 3.87, HBA 7, HBD 3, PSA 119.46, QED 0.39
Compound (SMILES): Nc1nc(-n2cccn2)nc(-n2cccn2)c1Br
InChIKey: ATFXVNUWQOXRRU-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Antagonist activity at human adenosine A3 receptor expressed in HeLa cells by radioligand competition binding assay
Measurement: Ki = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 306.13, ALogP 1.19, HBA 7, HBD 1, PSA 87.44, QED 0.77
Compound (SMILES): CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3cn(-c4ccccc4)nn3)n2)cc1
InChIKey: GJAQQKJDEHDCCU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HCT116 cells assessed as reduction in histone H2AX phosphorylation by Hoechst staining-based immunofluorescence microscopic analysis
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 420.5, ALogP 3.16, HBA 8, HBD 1, PSA 116.65, QED 0.53
Compound (SMILES): CC(C)(C)OC(=O)N1CC2CN(c3nc4ccccc4n(C4CCN(C5CCCCCCC5)CC4)c3=O)CC2C1
InChIKey: YPKXYQGFBGHFRA-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 135.8 nM (pChEMBL 6.869999885559082)
Descriptors: MW 549.76, ALogP 5.45, HBA 7, HBD 0, PSA 70.91, QED 0.51
Compound (SMILES): O=c1c(NCC(O)CO)nc2ccccc2n1[C@H]1C[C@H]2CC[C@@H](C1)N2C1CCCCCCC1
InChIKey: BKBGBNKHUNQUQH-PZDACTEOSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 224 nM (pChEMBL 6.650000095367432)
Descriptors: MW 454.62, ALogP 3.44, HBA 7, HBD 3, PSA 90.62, QED 0.62
Compound (SMILES): NC(=O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: LSINLLSZBVYZJF-BWTSREIZSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 408.55, ALogP 3.78, HBA 5, HBD 1, PSA 81.22, QED 0.84
Compound (SMILES): O=C(O)C1CCN(c2nc3ccccc3n([C@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)CC1
InChIKey: BIIKQRYVAUBKEY-UBRQYEGLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 657 nM (pChEMBL 6.179999828338623)
Descriptors: MW 492.66, ALogP 4.98, HBA 6, HBD 1, PSA 78.67, QED 0.65
Compound (SMILES): N[C@@H]1CCN(c2nc3ccccc3n([C@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)C1
InChIKey: SMXDKYPJJWXFLI-LGKPFJOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 14.9 nM (pChEMBL 7.829999923706055)
Descriptors: MW 449.64, ALogP 4.21, HBA 6, HBD 1, PSA 67.39, QED 0.76
Compound (SMILES): NC(=O)[C@H](CO)Nc1nc2ccccc2n([C@@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: YSTQEMAOTSXQDC-IIZPIQPGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 5350 nM (pChEMBL 5.269999980926514)
Descriptors: MW 467.61, ALogP 2.94, HBA 7, HBD 3, PSA 113.48, QED 0.6
Compound (SMILES): O=C(O)CNc1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: OBZVJUBYNSDNFQ-PMOLBWCYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 2840 nM (pChEMBL 5.550000190734863)
Descriptors: MW 438.57, ALogP 4.17, HBA 6, HBD 2, PSA 87.46, QED 0.73
Compound (SMILES): O=C(O)Cc1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: RSYJMTSEPZEHFW-AERCQKQUSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 19250 nM (pChEMBL 4.71999979019165)
Descriptors: MW 437.58, ALogP 4.69, HBA 5, HBD 1, PSA 75.43, QED 0.75
Compound (SMILES): O=C(O)CC1CCN(c2nc3ccccc3n([C@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)C1
InChIKey: HSXPNGSPJHVJRG-WIXXOLQWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 1203 nM (pChEMBL 5.920000076293945)
Descriptors: MW 492.66, ALogP 4.98, HBA 6, HBD 1, PSA 78.67, QED 0.63
Compound (SMILES): O=C(O)[C@@H](CO)Nc1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: UWTSOPBZAAXFLK-FCIYXJNOSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 998 nM (pChEMBL 6)
Descriptors: MW 468.6, ALogP 3.53, HBA 7, HBD 3, PSA 107.69, QED 0.6
Compound (SMILES): O=C1CCN(c2nc3ccccc3n(C3CCN(C4CCCCCCC4)CC3)c2=O)N1
InChIKey: BFATVKDIMUJHBW-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 381 nM (pChEMBL 6.420000076293945)
Descriptors: MW 423.56, ALogP 3.39, HBA 6, HBD 1, PSA 70.47, QED 0.82
Compound (SMILES): COc1ccc(NC(=O)c2nc3ccccc3n([C@@]3(C)C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)cn1
InChIKey: KYASHZYLJWGTDL-NGBRXVAQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 55.8 nM (pChEMBL 7.25)
Descriptors: MW 529.69, ALogP 5.51, HBA 7, HBD 1, PSA 89.35, QED 0.47
Compound (SMILES): CONC(=O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: CFUUKUMETCMVLI-PMOLBWCYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 438.57, ALogP 3.97, HBA 6, HBD 1, PSA 76.46, QED 0.73
Compound (SMILES): O=C(Nc1ccc(=O)[nH]c1)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: XWIXHXXFVCJUJZ-JKHIJQBDSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 501.63, ALogP 4.62, HBA 6, HBD 2, PSA 100.09, QED 0.54
Compound (SMILES): COc1ccc(NC(=O)c2nc3ccccc3n([C@@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)cn1
InChIKey: MQPHXDFBKUCNOD-BKFWDETESA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 743 nM (pChEMBL 6.130000114440918)
Descriptors: MW 515.66, ALogP 5.33, HBA 7, HBD 1, PSA 89.35, QED 0.49