lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NCC1CC1)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: UZDLGBNHYREMCH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: Human recombinant HDAC4 was expressed in full length form (aa 2-1084) in Sf9 insect cells (obtained from ATCC) using baculovirus generated with Bac-to-Bac system (Invitrogen). Test compounds were serially diluted to reach final test concentrations from 0.000128 uM to 10 uM. HDAC4 and test compounds were incubated in 25 mM Tris buffer pH 8.0 containing 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 0.05% (w/v) bovine serum albumine and 0.005% (v/v) Triton-X-100 for 2 hours at room temperature in presence of 5 uM of acetyl-Gly-Ala-Lys(E-trifluoroacetyl)-AMC (AMC=7-amino-4-methyl coumarin) in a final volume of 9 ul. Control wells with HDAC4 only (positive control).
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 311.26, ALogP 2.9, HBA 4, HBD 1, PSA 68.02, QED 0.94
Compound (SMILES): CC(C)CNC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: BAEVURPLUCNNJZ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: Human recombinant HDAC4 was expressed in full length form (aa 2-1084) in Sf9 insect cells (obtained from ATCC) using baculovirus generated with Bac-to-Bac system (Invitrogen). Test compounds were serially diluted to reach final test concentrations from 0.000128 uM to 10 uM. HDAC4 and test compounds were incubated in 25 mM Tris buffer pH 8.0 containing 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 0.05% (w/v) bovine serum albumine and 0.005% (v/v) Triton-X-100 for 2 hours at room temperature in presence of 5 uM of acetyl-Gly-Ala-Lys(E-trifluoroacetyl)-AMC (AMC=7-amino-4-methyl coumarin) in a final volume of 9 ul. Control wells with HDAC4 only (positive control).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 313.28, ALogP 3.14, HBA 4, HBD 1, PSA 68.02, QED 0.94
Compound (SMILES): C[C@H](CO)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: OVJXKZYFRSLKOB-SSDOTTSWSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: Human recombinant HDAC4 was expressed in full length form (aa 2-1084) in Sf9 insect cells (obtained from ATCC) using baculovirus generated with Bac-to-Bac system (Invitrogen). Test compounds were serially diluted to reach final test concentrations from 0.000128 uM to 10 uM. HDAC4 and test compounds were incubated in 25 mM Tris buffer pH 8.0 containing 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 0.05% (w/v) bovine serum albumine and 0.005% (v/v) Triton-X-100 for 2 hours at room temperature in presence of 5 uM of acetyl-Gly-Ala-Lys(E-trifluoroacetyl)-AMC (AMC=7-amino-4-methyl coumarin) in a final volume of 9 ul. Control wells with HDAC4 only (positive control).
Measurement: IC50 = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 315.25, ALogP 1.87, HBA 5, HBD 2, PSA 88.25, QED 0.9
Compound (SMILES): N#Cc1cc(S(=O)(=O)Nc2ccc(F)cn2)ccc1Oc1ccc(CO)c(Cl)c1
InChIKey: LSWMNYFPGSRIIB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 433.85, ALogP 3.83, HBA 6, HBD 2, PSA 112.31, QED 0.61
Compound (SMILES): O=S(=O)(c1ccccc1)N(Cc1ccc(F)c(C(F)(F)F)c1)c1nc2ccc(Cl)cn2c1Cl
InChIKey: DHXLOLBJAMMIQL-UHFFFAOYSA-N
Target: Transient receptor potential M8 protein (SINGLE PROTEIN), Canis lupus familiaris
UniProt: Q1A7N1
Assay: FLIPR Assay: The functional activity of compounds of the formula (I) was determined by measuring changes in intracellular calcium concentration using a Ca2+-sensitive fluorescent dye. The changes in fluorescent signal were monitored by a fluorescence plate reader, either a FLIPR (Molecular Devices) or FDSS (Hamamatsu). Increases in intracellular Ca2+ concentration were readily detected upon activation with icilin.At 24 hrs prior to assay, HEK293 cells stably expressing canine TRPM8 were seeded in culture medium in black wall, clear-base poly-D-lysine coated 384-well plates (BD Biosciences, NJ, USA) and grown overnight in 5% CO2 at 37° C. On assay day, growth media was removed and cells were loaded with Calcium 3 Dye (Molecular Devices) for 35 min at 37° C., under 5% CO2 and then for 25 min at room temperature and atmosphere.
Measurement: IC50 = 28.6 nM (pChEMBL 7.539999961853027)
Descriptors: MW 518.32, ALogP 6.19, HBA 4, HBD 0, PSA 54.68, QED 0.3
Compound (SMILES): CC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(Cl)c3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: DKZYXHCYPUVGAF-JCNLHEQBSA-N
Target: Tyrosine-protein kinase ABL2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42684
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 487.43, ALogP 6.04, HBA 6, HBD 2, PSA 78.35, QED 0.41
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3S(N)(=O)=O)cc2F)cn1
InChIKey: SXONKUBZFICRAY-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 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 344.37, ALogP 2.18, HBA 5, HBD 2, PSA 111.96, QED 0.76
Compound (SMILES): C[C@@H](NS(=O)(=O)c1ccccc1-c1ccc(-c2cnc(N)cn2)c(F)c1)C(F)(F)F
InChIKey: MMJYJAOZVYCUHZ-LLVKDONJSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence 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 pFastBacl (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 [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]. 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].
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 440.42, ALogP 3.76, HBA 5, HBD 2, PSA 97.97, QED 0.59
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3S(=O)(=O)N[C@@H]3CCc4ccccc43)cc2F)cn1
InChIKey: DVFDVBNWZABMIE-JOCHJYFZSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence 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 pFastBacl (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 [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]. 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].
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 460.53, ALogP 4.5, HBA 5, HBD 2, PSA 97.97, QED 0.46
Compound (SMILES): C[C@H](CO)NS(=O)(=O)c1ccccc1-c1ccc(-c2cnc(N)cn2)c(F)c1
InChIKey: UYLVAELNTHKHTI-GFCCVEGCSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in human whole blood assessed as reduction in LTB4 level preincubated for 15 mins followed by calcium ionophore A23187 addition and measured after 30 min
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 402.45, ALogP 2.19, HBA 6, HBD 3, PSA 118.2, QED 0.58
Compound (SMILES): CN1CCN(S(=O)(=O)c2ccccc2-c2ccc(-c3cnc(N)cn3)c(F)c2)CC1
InChIKey: NMRJITSYFSSBEJ-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence 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 pFastBacl (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 [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]. 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].
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 427.51, ALogP 2.47, HBA 6, HBD 1, PSA 92.42, QED 0.69
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3S(=O)(=O)N3CC[C@H](N)C3)cc2F)cn1
InChIKey: HNVMXIICKHNIJC-AWEZNQCLSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence 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 pFastBacl (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 [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]. 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].
Measurement: Ki = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 413.48, ALogP 2.25, HBA 6, HBD 2, PSA 115.2, QED 0.68
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3S(=O)(=O)N[C@H]3CCCC[C@@H]3O)cc2F)cn1
InChIKey: ZQPHTXPTKFVEIA-ICSRJNTNSA-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 = 1 nM (pChEMBL 9)
Descriptors: MW 442.52, ALogP 3.11, HBA 6, HBD 3, PSA 118.2, QED 0.56
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3CSc3nccc(N)n3)cc2F)cn1
InChIKey: FMYWOZJEAYVIEO-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 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 404.47, ALogP 4.2, HBA 7, HBD 2, PSA 103.6, QED 0.38
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2ccc(Cl)c([C@]3(C(F)F)N=C(N)O[C@H]4C[C@H]43)c2)cn1
InChIKey: OZDFQUNLUMSOKL-RAJNIJHNSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Fluorescence Resonance Energy Transfer Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 65800 nM (pChEMBL 4.179999828338623)
Descriptors: MW 447.83, ALogP 2.59, HBA 7, HBD 2, PSA 111.72, QED 0.66
Compound (SMILES): CC#CCOc1cnc(C(=O)Nc2ccc(Cl)c([C@@]3(CF)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: IOBHUULPCQQFMD-AVBTWRTFSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of recombinant Cathepsin D (unknown origin) expressed in CHO cells preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 = 1835 nM (pChEMBL 5.739999771118164)
Descriptors: MW 443.87, ALogP 2.68, HBA 7, HBD 2, PSA 111.72, QED 0.66
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(Cl)c([C@]3(CF)N=C(N)O[C@H]4C[C@H]43)c2)cn1
InChIKey: IHCBQIHTSNGMPW-LQGCGHSZSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: In Vitro Enzymatic FRET Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p 379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 86900 nM (pChEMBL 4.059999942779541)
Descriptors: MW 447.83, ALogP 2.43, HBA 7, HBD 2, PSA 111.72, QED 0.66
Compound (SMILES): N#Cc1cnc2c(Nc3ccc(Cl)c([C@]4(C(F)F)N=C(N)O[C@H]5C[C@H]54)c3)ncc(F)c2c1
InChIKey: SQFZDAOSJQBZRX-QTPGKHNVSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Fluorescence Resonance Energy Transfer Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 88357 nM (pChEMBL 4.050000190734863)
Descriptors: MW 458.83, ALogP 4.23, HBA 7, HBD 2, PSA 109.21, QED 0.61
Compound (SMILES): N#Cc1cnc2c(Nc3ccc(Cl)c([C@@]4(C(F)F)N=C(N)O[C@@H]5C[C@@H]54)c3)ncc(F)c2c1
InChIKey: SQFZDAOSJQBZRX-CQURBHOASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: In Vitro Enzymatic FRET Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 39.1 nM (pChEMBL 7.409999847412109)
Descriptors: MW 458.83, ALogP 4.23, HBA 7, HBD 2, PSA 109.21, QED 0.61
Compound (SMILES): NC1=N[C@@](c2cc(N[C@H]3CCc4cc(Br)cnc43)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: OANSAWVWHAEMIE-WBZSCFCESA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Fluorescence Resonance Energy Transfer Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 83300 nM (pChEMBL 4.079999923706055)
Descriptors: MW 467.29, ALogP 4.28, HBA 5, HBD 2, PSA 72.53, QED 0.7
Compound (SMILES): C[C@H](C(=O)NCc1cc(C(C)(C)C)nn1-c1cccc(Cl)c1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: WVJARZWJWNGZDX-HNNXBMFYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the rat-species vanilloid receptor 1 (VR1/TRPV1) can be determined using the following assay. In this assay, the influx of Ca2+ through the receptor channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Complete medium: 50 ml HAMS F12 nutrient mixture (Gibco Invitrogen GmbH, Karlsruhe, Germany) with10% by volume of FCS (foetal calf serum, Gibco Invitrogen GmbH, Karlsruhe, Germany, heat-inactivated);2 mM L-glutamine (Sigma, Munich, Germany);1% by weight of AA solution (antibiotic/antimyotic solution, PAA, Pasching, Austria) and 25 ng/ml NGF medium (2.5 S, Gibco Invitrogen GmbH, Karlsruhe, Germany).
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 507.03, ALogP 4.75, HBA 5, HBD 2, PSA 93.09, QED 0.48
Compound (SMILES): CC(C(=O)NCc1cc(C(F)(F)F)nn1-c1ccc(Cl)cc1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: QSMNOKNPEPLVBN-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: IC50 = 179 nM (pChEMBL 6.75)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 93.09, QED 0.45
Compound (SMILES): C[C@H](C(=O)NCc1cc(C(F)(F)F)nn1-c1ccc(Cl)cc1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: QSMNOKNPEPLVBN-LBPRGKRZSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: IC50 = 47.1 nM (pChEMBL 7.329999923706055)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 93.09, QED 0.45
Compound (SMILES): CC(C(=O)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: REFSKWWRGFCGDO-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: IC50 = 39.2 nM (pChEMBL 7.409999847412109)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 93.09, QED 0.45
Compound (SMILES): C[C@@H](C(=O)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: REFSKWWRGFCGDO-GFCCVEGCSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: IC50 = 2585 nM (pChEMBL 5.590000152587891)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 93.09, QED 0.45
Compound (SMILES): C[C@H](C(=O)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: REFSKWWRGFCGDO-LBPRGKRZSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 93.09, QED 0.45
Compound (SMILES): COc1cc(N2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: UAFDWTTZIJTWGE-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 514.55, ALogP 3.47, HBA 7, HBD 3, PSA 105.4, QED 0.4
Compound (SMILES): COc1cc(C2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: FJMPEQKEWCBVKU-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 0.74 nM (pChEMBL 9.130000114440918)
Descriptors: MW 513.56, ALogP 4.53, HBA 6, HBD 3, PSA 102.16, QED 0.39
Compound (SMILES): COc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: AWJVIOYPZZZYAX-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 527.59, ALogP 4.87, HBA 6, HBD 2, PSA 93.37, QED 0.41
Compound (SMILES): COc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2cccc(C(N)=O)c2)n1
InChIKey: JAXOLKSOAOTUCK-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 513.56, ALogP 4.94, HBA 6, HBD 2, PSA 93.37, QED 0.44
Compound (SMILES): CCc1cc(C2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: JMXXELDLOUPZFT-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 511.59, ALogP 5.08, HBA 5, HBD 3, PSA 92.93, QED 0.37
Compound (SMILES): CCc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: SXMOIWLLBKAOGR-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 525.62, ALogP 5.42, HBA 5, HBD 2, PSA 84.14, QED 0.39
Compound (SMILES): NC(=O)Cc1ccccc1CCc1nc(Nc2ccc(C3CCNCC3)cc2OC(F)(F)F)ncc1C(F)(F)F
InChIKey: WEXDYWPJRYUSAD-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 0.79 nM (pChEMBL 9.100000381469727)
Descriptors: MW 567.53, ALogP 5.42, HBA 6, HBD 3, PSA 102.16, QED 0.3
Compound (SMILES): CN1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4CC(N)=O)n3)c(OC(F)(F)F)c2)CC1
InChIKey: QSOOWIITUXDNSS-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 581.56, ALogP 5.76, HBA 6, HBD 2, PSA 93.37, QED 0.31
Compound (SMILES): COC(=O)N[C@@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: GXSHWBSAHCQKFV-OEDDDKJZSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 513.52, ALogP 4.38, HBA 6, HBD 3, PSA 119.23, QED 0.47
Compound (SMILES): COc1cc(C(F)(F)F)ccc1-c1ncnc2cc(S(=O)(=O)Nc3nccs3)ccc12
InChIKey: VSUDRCZPHWUXEW-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells assessed as inhibition of sodium current at holding potential of -125 mV measured for 3 to 5 mins by whole cell voltage clamp method
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 466.47, ALogP 4.58, HBA 7, HBD 1, PSA 94.07, QED 0.46
Compound (SMILES): COc1cc(-c2cccc(F)c2)c(Cl)cc1-c1nccc2cc(S(=O)(=O)Nc3ccncn3)ccc12
InChIKey: CUAWFKPONCJPMJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 520.97, ALogP 5.96, HBA 6, HBD 1, PSA 94.07, QED 0.3
Compound (SMILES): COc1cc(-c2cccc(F)c2)c(Cl)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12
InChIKey: PLEDPBLRULDFLA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 509.95, ALogP 6.16, HBA 6, HBD 1, PSA 94.32, QED 0.29
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CCO1
InChIKey: VXKBREQCYRAEHY-XUDSTZEESA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 312.45, ALogP 4.45, HBA 2, HBD 0, PSA 26.3, QED 0.62
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C(F)(F)F)c1c2=O
InChIKey: OICPOZZKXXBDTD-CYBMUJFWSA-N
Target: Prolyl endopeptidase FAP (SINGLE PROTEIN), Homo sapiens
UniProt: Q12884
Assay: Inhibition of FAP (unknown origin) preincubated for 20 mins followed by Nle-Pro-AMC addition measured for 40 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 479.44, ALogP 1.7, HBA 8, HBD 1, PSA 102.28, QED 0.57
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3ccccc3C#N)c1c2=O
InChIKey: PNGZLJFKFMSBJO-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of QPP (unknown origin) preincubated for 30 mins followed by Nle-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 418.46, ALogP 0.42, HBA 9, HBD 1, PSA 126.07, QED 0.65
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3F)c1c2=O
InChIKey: YAWOUZPWJKYFDX-CYBMUJFWSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of QPP (unknown origin) preincubated for 30 mins followed by Nle-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 429.43, ALogP 0.82, HBA 8, HBD 1, PSA 102.28, QED 0.66
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2nc3n(c(=O)c21)CC(=O)N3C
InChIKey: PPMZXTYNICRHMC-LLVKDONJSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay: DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37 C. The 30 ul assay solution contained 20 pM recombinant human DPP4 and 50 uM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37 C. prior to start of the experiment. Test compounds were serially diluted (3-fold) in 100% DMSO to avoid solubility issues; working solutions in 3% DMSO were prepared using assay buffer. 10 ul each of enzyme and compound solutions were mixed and pre-incubated at 37 C. for 30 minutes.
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 355.4, ALogP -0.48, HBA 8, HBD 1, PSA 102.28, QED 0.73
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3F)c1c2=O
InChIKey: ULGAIQGMBBLSSH-CQSZACIVSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay: DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37 C. The 30 ul assay solution contained 20 pM recombinant human DPP4 and 50 uM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37 C. prior to start of the experiment. Test compounds were serially diluted (3-fold) in 100% DMSO to avoid solubility issues; working solutions in 3% DMSO were prepared using assay buffer. 10 ul each of enzyme and compound solutions were mixed and pre-incubated at 37 C. for 30 minutes.
Measurement: IC50 = 625 nM (pChEMBL 6.199999809265137)
Descriptors: MW 443.46, ALogP 1.21, HBA 8, HBD 1, PSA 102.28, QED 0.65
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C(F)(F)F)c1c2=O
InChIKey: NHQURNPIJLKKLF-CQSZACIVSA-N
Target: Prolyl endopeptidase FAP (SINGLE PROTEIN), Homo sapiens
UniProt: Q12884
Assay: Inhibition of FAP (unknown origin) preincubated for 20 mins followed by Nle-Pro-AMC addition measured for 40 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 493.47, ALogP 2.09, HBA 8, HBD 1, PSA 102.28, QED 0.56
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C#N)c1c2=O
InChIKey: KMOYVYIQCXEQDG-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin) preincubated for 20 mins followed by Gly-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 436.45, ALogP 0.56, HBA 9, HBD 1, PSA 126.07, QED 0.64
Compound (SMILES): O=C(NCCO)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: NCMUYLGLYZSHBA-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition Assay: Human recombinant HDAC4 was expressed in full length form (aa 2-1084) in Sf9 insect cells (obtained from ATCC) using baculovirus generated with Bac-to-Bac system (Invitrogen). Test compounds were serially diluted to reach final test concentrations from 0.000128 uM to 10 uM. HDAC4 and test compounds were incubated in 25 mM Tris buffer pH 8.0 containing 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 0.05% (w/v) bovine serum albumine and 0.005% (v/v) Triton-X-100 for 2 hours at room temperature in presence of 5 uM of acetyl-Gly-Ala-Lys(E-trifluoroacetyl)-AMC (AMC=7-amino-4-methyl coumarin) in a final volume of 9 ul. Control wells with HDAC4 only (positive control) and without HDAC4 (negative control) were included on the microplate. Bovine trypsin (4.5 ul of a 300 nM solution) was added and the plate incubated for additional 15 minutes at room temperature. The plate was placed in a fluorescence microplate reader, and read at an excitation wavelength of 360 nm.
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 301.22, ALogP 1.48, HBA 5, HBD 2, PSA 88.25, QED 0.89
Compound (SMILES): N#Cc1cc(S(=O)(=O)Nc2ccc(F)cn2)ccc1Oc1ccc(CO)c(Cl)c1
InChIKey: LSWMNYFPGSRIIB-UHFFFAOYSA-N
Target: Solute carrier family 22 member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSA0
Assay: Inhibition of OAT4 (unknown origin)
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 433.85, ALogP 3.83, HBA 6, HBD 2, PSA 112.31, QED 0.61
Compound (SMILES): CC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(Cl)c3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: DKZYXHCYPUVGAF-JCNLHEQBSA-N
Target: Acyl-CoA dehydrogenase family member 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6JQN1
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 487.43, ALogP 6.04, HBA 6, HBD 2, PSA 78.35, QED 0.41