lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NC(=O)c1c(-c2ccc(NC(=O)Nc3ccccc3)cc2)nsc1NC(=O)NCCCN1CCOCC1
InChIKey: DVMIIUOULRDNLG-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 523.62, ALogP 3.4, HBA 7, HBD 5, PSA 150.71, QED 0.27
Compound (SMILES): Cc1ccc(F)c(NC(=O)Nc2ccc(-c3nsc(NC(=O)NCCCN4CCOCC4)c3C(N)=O)cc2)c1
InChIKey: FAIYNQQPUQQMIC-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 555.64, ALogP 3.84, HBA 7, HBD 5, PSA 150.71, QED 0.25
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(-c3nsc(NC(=O)NCCCN4CCOCC4)c3C(N)=O)cc2)c1
InChIKey: CNIWCJQSFDYIDI-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 537.65, ALogP 3.71, HBA 7, HBD 5, PSA 150.71, QED 0.26
Compound (SMILES): NC(=O)c1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)cc2)nsc1NC(=O)NCCCN1CCOCC1
InChIKey: FWBUUGDBUKHCQX-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 609.61, ALogP 4.55, HBA 7, HBD 5, PSA 150.71, QED 0.18
Compound (SMILES): Cc1ccc(NC(=O)Nc2ccc(-c3nsc(NC(=O)NCCCN4CCOCC4)c3C(N)=O)cc2)cc1
InChIKey: HHPVWJJNJSJOLQ-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 537.65, ALogP 3.71, HBA 7, HBD 5, PSA 150.71, QED 0.26
Compound (SMILES): COCCCNC(=O)Nc1snc(-c2ccc(N)cc2)c1C(N)=O
InChIKey: LDCQPCHMNOJESG-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 349.42, ALogP 1.65, HBA 6, HBD 4, PSA 132.36, QED 0.45
Compound (SMILES): NC(=O)c1c(-c2ccc(NC(=O)c3cccc(C(F)(F)F)c3)cc2)nsc1NC(=O)NCCCN1CCOCC1
InChIKey: JJKVPTCDYLGUKC-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 576.6, ALogP 4.02, HBA 7, HBD 4, PSA 138.68, QED 0.28
Compound (SMILES): Cc1ccncc1-c1cccc2c(-c3ccccc3)noc12
InChIKey: OQORIDVPVHCIRH-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 286.33, ALogP 4.87, HBA 3, HBD 0, PSA 38.92, QED 0.53
Compound (SMILES): Cc1c([C@@H](O)CN2CCN(C[C@H](O)c3ccc4c(c3C)COC4=O)CC2)ccc2c1COC2=O
InChIKey: OCKGFTQIICXDQW-ZEQRLZLVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG after 6 mins by electrophysiological assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 466.53, ALogP 2.03, HBA 8, HBD 2, PSA 99.54, QED 0.62
Compound (SMILES): Cc1c([C@H](O)CN2CCN(C[C@@H](O)c3ccc4c(c3C)COC4=O)CC2)ccc2c1COC2=O
InChIKey: OCKGFTQIICXDQW-DNQXCXABSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]MK-499 from human ERG
Measurement: IC50 = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 466.53, ALogP 2.03, HBA 8, HBD 2, PSA 99.54, QED 0.62
Compound (SMILES): Cc1c([C@H](O)CN2CCN(C[C@H](O)c3ccc4c(c3C)COC4=O)CC2)ccc2c1COC2=O
InChIKey: OCKGFTQIICXDQW-PSWAGMNNSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]MK-499 from human ERG
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 466.53, ALogP 2.03, HBA 8, HBD 2, PSA 99.54, QED 0.62
Compound (SMILES): Cc1c(CCN2CCN(CC(O)c3ccc4c(c3C)COC4=O)CC2)ccc2c1COC2=O
InChIKey: FRTFPWJYBDIGEF-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir 1.1 (ROMKl) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391 : 85- 100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, CA). Chinese hamster ovary cells stably expressing Kirl.l channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 0C. Prior to an experiment, Kirl .l expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 ml of Versene (Invitrogen 15040-066) for approximately 6 min at 37 0C and suspended in 10 ml of bath solution containing (in roM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES5 pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 ml of bath solution and placed in the Ion Works instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF5 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 450.54, ALogP 2.54, HBA 7, HBD 1, PSA 79.31, QED 0.68
Compound (SMILES): C[C@H]1Cn2cc(C(N)=O)nc2-c2cc(C#CC(C)(C)O)ccc2O1
InChIKey: FCLUEVDLZSWFCZ-NSHDSACASA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) after 1 to 2 hrs by ADP-FP assay
Measurement: Ki = 547 nM (pChEMBL 6.260000228881836)
Descriptors: MW 325.37, ALogP 1.55, HBA 5, HBD 2, PSA 90.37, QED 0.78
Compound (SMILES): C[C@@H]1Cn2cc(C(N)=O)nc2-c2cc(C#CC(C)(C)O)ccc2O1
InChIKey: FCLUEVDLZSWFCZ-LLVKDONJSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 325.37, ALogP 1.55, HBA 5, HBD 2, PSA 90.37, QED 0.78
Compound (SMILES): CN(C)C1COc2cc(F)c(C#CC(C)(O)c3ccccn3)cc2-c2nc(C(N)=O)sc21
InChIKey: VZWASDXIWDPOPT-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 452.51, ALogP 2.7, HBA 7, HBD 2, PSA 101.57, QED 0.59
Compound (SMILES): Cn1nccc1Cc1c(C(N)=O)nc2n1CCOc1cc(F)c(C#CC(C)(C)O)cc1-2
InChIKey: YEIUTWFMRCCWQY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 423.45, ALogP 1.63, HBA 7, HBD 2, PSA 108.19, QED 0.62
Compound (SMILES): COC[C@@](C)(O)C#Cc1cc2c(cc1F)C1CC(C1)n1c-2nc(C(N)=O)c1[C@H](O)c1ccnn1C
InChIKey: CEDFAOFDDPOULD-IXPZBHSUSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 479.51, ALogP 1.78, HBA 8, HBD 3, PSA 128.42, QED 0.48
Compound (SMILES): COC[C@](C)(O)C#Cc1cc2c(cc1F)C1CC(C1)n1c-2nc(C(N)=O)c1[C@H](O)c1ccnn1C
InChIKey: CEDFAOFDDPOULD-MWSNSZIRSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 479.51, ALogP 1.78, HBA 8, HBD 3, PSA 128.42, QED 0.48
Compound (SMILES): CN1CC[C@@](O)(C#Cc2cc3c(cc2F)C2CC(C2)n2c-3nc(C(N)=O)c2[C@H](O)c2ccnn2C)C1=O
InChIKey: AZAFMASCHOZXJQ-WUUBFYFJSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 504.52, ALogP 0.98, HBA 8, HBD 3, PSA 139.5, QED 0.45
Compound (SMILES): CN1CC[C@@](O)(C#Cc2cc3c(cc2F)C2CC(C2)n2c-3nc(C(N)=O)c2[C@@H](O)c2ccnn2C)C1=O
InChIKey: AZAFMASCHOZXJQ-OTNPQCEHSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 504.52, ALogP 0.98, HBA 8, HBD 3, PSA 139.5, QED 0.45
Compound (SMILES): CN1CC[C@](O)(C#Cc2cc3c(cc2F)C2CC(C2)n2c-3nc(C(N)=O)c2[C@H](O)c2ccnn2C)C1=O
InChIKey: AZAFMASCHOZXJQ-IFHKZOIYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 504.52, ALogP 0.98, HBA 8, HBD 3, PSA 139.5, QED 0.45
Compound (SMILES): CN1CC[C@](O)(C#Cc2cc3c(cc2F)C2CC(C2)n2c-3nc(C(N)=O)c2[C@@H](O)c2ccnn2C)C1=O
InChIKey: AZAFMASCHOZXJQ-AJDSKFFFSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 504.52, ALogP 0.98, HBA 8, HBD 3, PSA 139.5, QED 0.45
Compound (SMILES): COC[C@](C)(O)C#Cc1cc2c(cc1F)C1CC(C1)n1c-2nc(C(N)=O)c1[C@@H](O)c1ccnn1C
InChIKey: CEDFAOFDDPOULD-KKKMIPKYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 479.51, ALogP 1.78, HBA 8, HBD 3, PSA 128.42, QED 0.48
Compound (SMILES): COC[C@@](C)(O)C#Cc1cc2c(cc1F)C1CC(C1)n1c-2nc(C(N)=O)c1[C@@H](O)c1ccnn1C
InChIKey: CEDFAOFDDPOULD-OMBFLKOESA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 479.51, ALogP 1.78, HBA 8, HBD 3, PSA 128.42, QED 0.48
Compound (SMILES): CCCNc1cnn(C2CC(C)(C)CC(C)(C)C2)c(=O)c1Cl
InChIKey: YMCXJOJJPKTDCH-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Radioligand Binding Assay: Plasma membranes prepared from HEK 293 EBNA cells transfected with human CB1 or CB2 cannabinoid receptors (3.7 or 3.3 .mu.mol/mg protein, receptor concentration; PerkinElmer) were used for the radioligand binding studies. The composition of incubation buffer for CB1 assay was 50 mM Tris base, 2.5 mM EDTA, 5 mM MgCl.sub.2 and 0.5 mg/ml fatty acid free BSA and for CB2 assay was 50 mM Tris base, 2.5 mM EGTA, 5 mM MgCl.sub.2 and 1 mg/ml fatty acid free BSA; pH was adjusted to 7.4 by adding 1N HCl. Plasma membranes were diluted with incubation buffer to provide a final protein concentration of 2.4 .mu.g (CB1) or 8 .mu.g (CB2) per well in non-binding surface polystyrene 96-well assay plates (Corning). Compound solutions were prepared in silanized glass tubes and dispensed using pipette tips with SUPERSLIK.TM. surface. Competition studies were performed using a final concentration of 0.72 nM [.sup.3H]-CP 55,940 (100-180 Ci/mmol, specific activity; PerkinElmer) against test compounds.
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 325.88, ALogP 4.5, HBA 4, HBD 1, PSA 46.92, QED 0.89
Compound (SMILES): CC1(C)CC(n2ncc(NCCN3CCOCC3)c(Br)c2=O)CC(C)(C)C1
InChIKey: LFSXWIRCSGJIBI-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Radioligand Binding Assay: Plasma membranes prepared from HEK 293 EBNA cells transfected with human CB1 or CB2 cannabinoid receptors (3.7 or 3.3 pmol/mg protein, receptor concentration; PerkinElmer) were used for the radioligand binding studies. The composition of incubation buffer for CB1 assay was 50 mM Tris base, 2.5 mM EDTA, 5 mM MgCl2 and 0.5 mg/ml fatty acid free BSA and for CB2 assay was 50 mM Tris base, 2.5 mM EGTA, 5 mM MgCl2 and 1 mg/ml fatty acid free BSA; pH was adjusted to 7.4 by adding 1N HCl. Plasma membranes were diluted with incubation buffer to provide a final protein concentration of 2.4 μg (CB1) or 8 μg (CB2) per well in non-binding surface polystyrene 96-well assay plates (Corning). Compound solutions were prepared in silanized glass tubes and dispensed using pipette tips with SUPERSLIK¿ surface. Competition studies were performed using a final concentration of 0.72 nM [3H]-CP 55,940 (100-180 Ci/mmol, specific activity; PerkinElmer) against test compounds. Non-specific binding was determined using 10 uM of unlabeled CP 55,940. Incubations were performed in 96-well assay plates at a final volume of 200 ul for 90 min (CB1) or 60 min (CB2) at room temperature. Binding reactions were terminated by the addition of ice-cold incubation buffer and rapid filtration through a glass fiber filter using a cell harvester (Inotech). This was followed by 8 additional washes. The glass fiber filter (0.26 mm thickness, 1-1.5 um retention; Inotech) was presoaked in cold incubation buffer containing 0.05% polyethylenimine. The filters were oven-dried at 50° C. for 60 min and counting performed using a Beckman Coulter LS 6500 Multi-Purpose Scintillation Counter (Beckman-Coulter). Binding was determined in duplicate for at least 4 separate experiments.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 441.41, ALogP 3.53, HBA 6, HBD 1, PSA 59.39, QED 0.76
Compound (SMILES): CN(C)CCN(C)c1cnn(C2CC(C)(C)CC(C)(C)C2)c(=O)c1Cl
InChIKey: VTKUBMALEHEFPX-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Radioligand Binding Assay: Plasma membranes prepared from HEK 293 EBNA cells transfected with human CB1 or CB2 cannabinoid receptors (3.7 or 3.3 .mu.mol/mg protein, receptor concentration; PerkinElmer) were used for the radioligand binding studies. The composition of incubation buffer for CB1 assay was 50 mM Tris base, 2.5 mM EDTA, 5 mM MgCl.sub.2 and 0.5 mg/ml fatty acid free BSA and for CB2 assay was 50 mM Tris base, 2.5 mM EGTA, 5 mM MgCl.sub.2 and 1 mg/ml fatty acid free BSA; pH was adjusted to 7.4 by adding 1N HCl. Plasma membranes were diluted with incubation buffer to provide a final protein concentration of 2.4 .mu.g (CB1) or 8 .mu.g (CB2) per well in non-binding surface polystyrene 96-well assay plates (Corning). Compound solutions were prepared in silanized glass tubes and dispensed using pipette tips with SUPERSLIK.TM. surface. Competition studies were performed using a final concentration of 0.72 nM [.sup.3H]-CP 55,940 (100-180 Ci/mmol, specific activity; PerkinElmer) against test compounds.
Measurement: IC50 = 2630 nM (pChEMBL 5.579999923706055)
Descriptors: MW 368.95, ALogP 3.67, HBA 5, HBD 0, PSA 41.37, QED 0.79
Compound (SMILES): Cc1cc2ccccc2n1-c1nc2c(c(NCc3ccccc3)n1)CNCC2
InChIKey: KEXDPSXGMWVJRT-UHFFFAOYSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Inhibition of p97 ATPase in human A549 cells assessed as accumulation of CHOP poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay
Measurement: IC50 = 9150 nM (pChEMBL 5.039999961853027)
Descriptors: MW 369.47, ALogP 3.99, HBA 5, HBD 2, PSA 54.77, QED 0.57
Compound (SMILES): O=C(O)c1ccc2c(c1)[nH]c(=O)c1ccncc12
InChIKey: FNBQKJSMQWRTEK-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: In Vitro Cell-Free Assay: Test compounds in aqueous solution were added at a volume of 10 microliters, to a reaction mixture comprising 10 microliters Assay Dilution Buffer (ADB; 20 mM MOPS, pH 7.2, 25 mM beta-glycerolphosphate, 5 mM EGTA, 1 mM sodium orthovanadate and 1 mM dithiothreitol), 10 microliters of substrate peptide (RRRDDDSDDD, dissolved in ADB at a concentration of 1 mM), 10 microliters of recombinant human CK2 (25 ng dissolved in ADB; Upstate). Reactions were initiated by the addition of 10 microliters of ATP Solution (90% 75 mM MgCl2, 75 micromolar ATP dissolved in ADB; 10% [gamma-33P]ATP (stock 1 mCi/100 ul; 3000 Ci/mmol (Perkin Elmer) and maintained for 10 minutes at 30 degrees C. The reactions were quenched with 100 microliters of 0.75% phosphoric acid, then transferred to and filtered through a phosphocellulose filter plate (Millipore). After washing each well 5 times with 0.75% phosphoric acid, the plate was dried under vacuum for 5 min.
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 240.22, ALogP 1.77, HBA 3, HBD 2, PSA 83.05, QED 0.63
Compound (SMILES): COc1cc([S+]([O-])c2ccccc2)cc2c3c(oc12)CCNC3
InChIKey: YWYGTUVVTYHDMB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Radioligand Binding Assay: For binding analysis vs. the human receptor, samples were incubated in 50 mM Tris-HCl, pH 7.5, 5 mM MgCl2, 1 mM EDTA (4% DMSO final) with 10 nM [N-methyl-3H]-LSD (Perkin Elmer), 2.5 ng of human 5-HT6 receptor membranes (Millipore) and 50 ug SPA beads (PVT-PEI-WGA, GE Healthcare) per well in a final volume of 0.2 mL. For binding analysis vs. the rat receptor, samples were incubated in the same buffer with 3.5 nM [N-methyl-3H]-LSD, 50 ug of rat 5-HT6 receptor membranes (Perkin Elmer) and 0.4 mg SPA beads (PVT-PEI-WGA Type B, GE Healthcare) per well also in a final volume of 0.2 mL. Binding reactions were performed in PicoPlate96 microtiter plates (Perkin Elmer) by consecutively adding 50 uL of each competing compound or buffer, SPA beads, radioligand and 5-HT6 receptor membranes. After an overnight incubation at room temperature on a Nutator mixer, plates were centrifuged for 15 min at 1,500 rpm, followed by incubation in the dark for 10 min.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 327.4, ALogP 3.25, HBA 4, HBD 1, PSA 57.46, QED 0.75
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3Oc3ncccn3)cc2F)cn1
InChIKey: APXMBHWSNKRFRO-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 359.36, ALogP 4.11, HBA 6, HBD 1, PSA 86.81, QED 0.59
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1ccccc1-c1ccc(-c2cn3cc(C(N)=O)ccc3n2)c(F)c1
InChIKey: DWSBTOKGRIBIBS-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 466.54, ALogP 3.98, HBA 5, HBD 2, PSA 106.56, QED 0.46
Compound (SMILES): Nc1ncc(-c2ccc(-c3ccccc3OCC(=O)O)cc2F)cn1
InChIKey: GJHIQVDUCYGFQU-UHFFFAOYSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 339.33, ALogP 3, HBA 5, HBD 2, PSA 98.33, QED 0.74
Compound (SMILES): Nc1ccc(-c2ccc(-c3ccccc3S(=O)(=O)N3C[C@@H]4C[C@H]3CO4)cc2F)cn1
InChIKey: NELGVJOKSYDWGT-IRXDYDNUSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 425.49, ALogP 3.3, HBA 5, HBD 1, PSA 85.52, QED 0.69
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(CN4CCOCC4)cc3)cc(N(C)C3CCCC3)c2C)c(=O)[nH]1
InChIKey: XMEUHPWGPJFKLD-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 542.72, ALogP 5.11, HBA 5, HBD 2, PSA 77.67, QED 0.41
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1C2CCCC1c1nnc(-c3ncccn3)n1C2
InChIKey: FCWVNMGJKGGYLS-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Ca2+ Flux Assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)).
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 448.84, ALogP 4.16, HBA 6, HBD 0, PSA 76.8, QED 0.59
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@H]2CCC[C@@H]1c1nnc(-c3ncccn3)n1C2
InChIKey: FCWVNMGJKGGYLS-SMDDNHRTSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Ca2+ Flux Assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)).
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 448.84, ALogP 4.16, HBA 6, HBD 0, PSA 76.8, QED 0.59
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@@H]2CCC[C@H]1c1nnc(-c3ncccn3)n1C2
InChIKey: FCWVNMGJKGGYLS-RISCZKNCSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding: Human or rat P2X7-1321N1 cells were collected and frozen @-80.degree. C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 .mu.l:10 .mu.l compound (10.times.)+(b) 40 .mu.l tracer (2.5.times.)+50 .mu.l membrane (2.times.). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2009, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4.degree. C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 448.84, ALogP 4.16, HBA 6, HBD 0, PSA 76.8, QED 0.59
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1C2CCCC1c1nnc(-c3ccc(F)cc3)n1C2
InChIKey: NRHCTGLCTSKNEY-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 464.85, ALogP 5.51, HBA 4, HBD 0, PSA 51.02, QED 0.47
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@H]2CCC[C@@H]1c1nnc(-c3ccc(F)cc3)n1C2
InChIKey: NRHCTGLCTSKNEY-WMLDXEAASA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 464.85, ALogP 5.51, HBA 4, HBD 0, PSA 51.02, QED 0.47