lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CC=C(c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)CC1
InChIKey: JIHSVBWAKKLMNO-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 552.62, ALogP 5.4, HBA 5, HBD 1, PSA 65.54, QED 0.43
Compound (SMILES): CN1CC=C(c2ccc(C(F)(F)F)cc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)CC1
InChIKey: GPFJATGTAHFICK-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 552.62, ALogP 5.4, HBA 5, HBD 1, PSA 65.54, QED 0.43
Compound (SMILES): CN1CCN(c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)CC1
InChIKey: JMHSSFSYBUYYML-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 555.62, ALogP 4.43, HBA 6, HBD 1, PSA 68.78, QED 0.47
Compound (SMILES): Cc1cn(-c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)cn1
InChIKey: MVOYXQLNULAYDH-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 7340 nM (pChEMBL 5.130000114440918)
Descriptors: MW 537.56, ALogP 5.18, HBA 6, HBD 1, PSA 80.12, QED 0.36
Compound (SMILES): Cc1cncn1-c1cc(C(F)(F)F)ccc1-c1cccc2c1CCN(S(=O)(=O)Nc1ncc(F)s1)C2
InChIKey: KCAFDAXZAOOGJL-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 537.56, ALogP 5.18, HBA 6, HBD 1, PSA 80.12, QED 0.36
Compound (SMILES): O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2c(Br)cc(C(F)(F)F)cc2C2=CCNCC2)C1
InChIKey: BPHPTRAVFDEGTB-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 600.49, ALogP 5.08, HBA 6, HBD 2, PSA 87.22, QED 0.43
Compound (SMILES): COc1cc(C(F)(F)F)cc(C2=CCNCC2)c1-c1cccc2c1CCN(S(=O)(=O)Nc1ccncn1)C2
InChIKey: YWWAYPYVBCLLLY-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 6190 nM (pChEMBL 5.210000038146973)
Descriptors: MW 545.59, ALogP 4.26, HBA 6, HBD 2, PSA 96.45, QED 0.48
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Ribosomal protein S6 kinase alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15418
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): O=C(Nc1csc(-c2nncn2C2CC2)n1)c1cc(-n2cnc(C3CC3)c2)c(N2CCOCC2)cn1
InChIKey: HIQBMNWLSRWMLZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.44 nM (pChEMBL 8.84000015258789)
Descriptors: MW 503.59, ALogP 3.28, HBA 11, HBD 1, PSA 115.88, QED 0.41
Compound (SMILES): CC1(O)CN(c2cnc(C(=O)Nc3csc(-c4nncn4C4CC4)n3)cc2-n2cnc(C3CC3)c2)C1
InChIKey: NJWBDKFUMFVDNV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.58 nM (pChEMBL 8.800000190734863)
Descriptors: MW 503.59, ALogP 3.02, HBA 11, HBD 2, PSA 126.88, QED 0.39
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCOCC3)cn2)cs1)C(F)(F)F
InChIKey: MELCFJDTTAZADC-AWEZNQCLSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2.62 nM (pChEMBL 8.579999923706055)
Descriptors: MW 559.58, ALogP 4.07, HBA 11, HBD 1, PSA 115.88, QED 0.36
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CC(C)(O)C3)cn2)cs1)C(F)(F)F
InChIKey: UYKUWFVECUXJLS-ZDUSSCGKSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.69 nM (pChEMBL 8.770000457763672)
Descriptors: MW 559.58, ALogP 3.81, HBA 11, HBD 2, PSA 126.88, QED 0.35
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N(C)C)cn2)cs1)C(F)(F)F
InChIKey: RLSCTEQIUJARIV-LBPRGKRZSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.88 nM (pChEMBL 8.729999542236328)
Descriptors: MW 517.54, ALogP 4.3, HBA 10, HBD 1, PSA 106.65, QED 0.39
Compound (SMILES): O=C(Nc1csc(-c2nncn2C2CC2)n1)c1cc(-n2cnc(C3CC3)c2)c(N2CCC2)cn1
InChIKey: DCJRKVUYWUYOAK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 473.57, ALogP 3.66, HBA 10, HBD 1, PSA 106.65, QED 0.44
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCC3)cn2)cs1)C(F)(F)F
InChIKey: NXORGDZYJJFVBX-ZDUSSCGKSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 529.55, ALogP 4.45, HBA 10, HBD 1, PSA 106.65, QED 0.38
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCCC3)cn2)cs1)C(F)(F)F
InChIKey: ITXKFABJUPGBQB-AWEZNQCLSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 543.58, ALogP 4.84, HBA 10, HBD 1, PSA 106.65, QED 0.36
Compound (SMILES): O=C(Nc1csc(-c2nncn2C2CC2)n1)c1cc(-n2cnc(C3CC3)c2)c(N2CCCC2)cn1
InChIKey: XBRXHRRXQWRKBE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 487.59, ALogP 4.05, HBA 10, HBD 1, PSA 106.65, QED 0.42
Compound (SMILES): O=C(Nc1csc(-c2nncn2C2CC2)n1)c1cc(-n2cnc(C3CC3)c2)c(N2CCC(O)C2)cn1
InChIKey: OYQMZDDDXIGQFI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 503.59, ALogP 3.02, HBA 11, HBD 2, PSA 126.88, QED 0.39
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCC(O)C3)cn2)cs1)C(F)(F)F
InChIKey: ZCPPMCSIWGHRLA-CFMCSPIPSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 559.58, ALogP 3.81, HBA 11, HBD 2, PSA 126.88, QED 0.35
Compound (SMILES): O=C(Nc1csc(-c2nncn2C2CC2)n1)c1cc(-n2cnc(C3CC3)c2)c(N2CCCCC2)cn1
InChIKey: MPBCXZFLFOKYBG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 501.62, ALogP 4.44, HBA 10, HBD 1, PSA 106.65, QED 0.4
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCCCC3)cn2)cs1)C(F)(F)F
InChIKey: ZOJDZQWISFZXHI-HNNXBMFYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 557.61, ALogP 5.23, HBA 10, HBD 1, PSA 106.65, QED 0.33
Compound (SMILES): CC(C)(Cc1nc2cc(OCc3ccc4ccccc4n3)ccc2n1Cc1ccc(-n2nccn2)cc1)C(=O)O
InChIKey: ZLKLUVPHHKRUAI-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 532.6, ALogP 5.45, HBA 8, HBD 1, PSA 107.95, QED 0.26
Compound (SMILES): O=C(O)[C@H]1CCCCC1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(Br)cc1
InChIKey: PKOYWFOHHRGCON-KEKNWZKVSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 576.52, ALogP 7.39, HBA 6, HBD 1, PSA 77.24, QED 0.22
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(Br)cc1
InChIKey: PKOYWFOHHRGCON-FCHUYYIVSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 576.52, ALogP 7.39, HBA 6, HBD 1, PSA 77.24, QED 0.22
Compound (SMILES): CC1(C)C(c2nc3cc(OCc4nc5ccccc5s4)ccc3n2Cc2ccc(Br)cc2)[C@H]1C(=O)O
InChIKey: MMLYXRWVZASXHB-BBMPLOMVSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 562.49, ALogP 6.86, HBA 6, HBD 1, PSA 77.24, QED 0.23
Compound (SMILES): O=C(O)[C@@H]1CCCCC1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(Br)cc1
InChIKey: PKOYWFOHHRGCON-FOIFJWKZSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 576.52, ALogP 7.39, HBA 6, HBD 1, PSA 77.24, QED 0.22
Compound (SMILES): CCC(CC)(Cc1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(Br)cc1)C(=O)O
InChIKey: BICKZVYJKORXKM-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 578.53, ALogP 7.47, HBA 6, HBD 1, PSA 77.24, QED 0.19
Compound (SMILES): COc1ncc(-c2ccc(Cn3c([C@H]4CCCC[C@H]4C(=O)O)nc4cc(OCc5nc6ccccc6s5)ccc43)cc2)cn1
InChIKey: VKYUIQKRODVFRU-IZZNHLLZSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 605.72, ALogP 7.1, HBA 9, HBD 1, PSA 112.25, QED 0.19
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(-c2cncnc2)cc1
InChIKey: GJNLEKAYYLZNSF-IZZNHLLZSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 575.69, ALogP 7.09, HBA 8, HBD 1, PSA 103.02, QED 0.21
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(-c2ccc(C(F)(F)F)nc2)cc1
InChIKey: YCKRYZSZZLLPOZ-IZZNHLLZSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 642.7, ALogP 8.71, HBA 7, HBD 1, PSA 90.13, QED 0.18
Compound (SMILES): COc1ccc(-c2ccc(Cn3c([C@H]4CCCC[C@H]4C(=O)O)nc4cc(OCc5nc6ccccc6s5)ccc43)cc2)cn1
InChIKey: CKTRIHBHQJSVJA-RRPNLBNLSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 604.73, ALogP 7.7, HBA 8, HBD 1, PSA 99.36, QED 0.18
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(-c2ncccn2)cc1
InChIKey: SWBVCKJHQJDHEU-LOSJGSFVSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 575.69, ALogP 7.09, HBA 8, HBD 1, PSA 103.02, QED 0.21
Compound (SMILES): CCC(CC)(Cc1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(-c2ncccn2)cc1)C(=O)O
InChIKey: RCQZBLBAGUFMMC-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 577.71, ALogP 7.16, HBA 8, HBD 1, PSA 103.02, QED 0.17
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(N2CCCCC2)cc1
InChIKey: ONMWMWRKFGRSIS-RRPNLBNLSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 580.75, ALogP 7.62, HBA 7, HBD 1, PSA 80.48, QED 0.2
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3ccc4ccccc4n3)ccc2n1Cc1ccc(Br)cc1
InChIKey: SBLFULGYUXMXLD-IZZNHLLZSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 570.49, ALogP 7.33, HBA 5, HBD 1, PSA 77.24, QED 0.22
Compound (SMILES): O=C(O)[C@H]1CCCC[C@H]1c1nc2cc(OCc3ccc4ccccc4n3)ccc2n1Cc1ccc(Br)cc1
InChIKey: SBLFULGYUXMXLD-FTJBHMTQSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 570.49, ALogP 7.33, HBA 5, HBD 1, PSA 77.24, QED 0.22
Compound (SMILES): O=C(O)[C@@H]1CCCC[C@@H]1c1nc2cc(OCc3ccc4ccccc4n3)ccc2n1Cc1ccc(OC(F)(F)F)cc1F
InChIKey: HHTSKRULZHVWQT-LOSJGSFVSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 ug/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.
Measurement: Ki = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 593.58, ALogP 7.61, HBA 6, HBD 1, PSA 86.47, QED 0.19
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of NaV1.7 (unknown origin) by electrophysiology assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CCc1cccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)c1
InChIKey: UHPDJNKZEVRIHV-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition Assay: Assay compound plates were prepared by diluting the compounds of formula (I) with chloride-free buffer (125 mM Na-gluconate, 4.8 mM K-gluconate, 1.3 mM Ca-gluconate, 1.2 mM KH2PO4, 1.2 mM MgSO4, 5.6 mM D-glucose, 25 mM HEPES, pH 7.4 with NaOH) in 100% DMSO to a final concentration of 1% DMSO. [14C]-Uric Uric acid working stock was made by addition of radiolabeled compound to a final concentration of 120 nM in chloride-free buffer. In all wells, the final assay concentration of solvent (DMSO) was 0.25%; the final assay concentration of [14C]-uric acid was 30 nM in chloride-free buffer and the final compound of formula (I) concentrations ranged from 0 to 10 uM. The vehicle comparator was DMSO (i.e. no inhibition of uric acid transport) and the pharmacological blockade (i.e. 100% inhibition of uric acid transport) was defined by benzbromarone at 10 uM final assay concentration.After pre-incubation, cells were washed with 50 uL of chloride-free buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 397.43, ALogP 4.25, HBA 5, HBD 1, PSA 92.08, QED 0.67