lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@@H](NC(=O)c1cc(C(=O)NCC2CCCCC2)n2c1CCCC2)c1ccccc1
InChIKey: XXNWMINYOUBVGX-JOCHJYFZSA-N
Target: Potassium channel subfamily K member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14649
Assay: TASK-1 Inhibiition Assay: Human TASK-1 channels were expressed in Xenopus oocytes. For this purpose, oocytes were isolated from Xenopus laevis and defoliculated. Subsequently, TASK-1-encoding RNA synthesized in vitro was injected into the oocytes. After two days of TASK-1 protein expression, TASK-1 currents were measured by two-microelectrode voltage clamp. Data were acquired and analyzed using a TEC-10cx amplifier (NPI Electronic, Tamm, Germany) connected to an ITC-16 interface (Instrutech Corp., Long Island, USA) and Pulse software (HEKA Elektronik, Lambrecht, Germany). Oocytes were clamped to -90 mV and TASK-1 mediated currents were measured during 500 ms voltage pulses to 40 mV. Oocytes were continuously superfused with ND96 buffer containing 96 mM sodium chloride, 2 mM potassium chloride, 1.8 mM calcium chloride, 1 mM magnesium chloride, 5 mM 4-(2-hydroxyethyl)-piperazine-1-ethanesulfonic acid (HEPES; pH adjusted to 7.4 with sodium hydroxide). All experiments were performed at room temperature.
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 421.59, ALogP 5.02, HBA 3, HBD 2, PSA 63.13, QED 0.66
Compound (SMILES): Cn1ncc(NC(=O)c2csc(-c3c(F)ccc(S(C)(=O)=O)c3F)n2)c1[C@@H]1CC[C@@H](N)[C@H](F)CO1
InChIKey: GCPYNKDBHSSQNT-JMSVASOKSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: PIM Kinase Binding Assay: LC3K assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO. PIM reactions were carried out in a final volume of 10 μL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 μL 2×ATP and test compound to 5 μL of 2× enzyme and FAM-peptide, contained 20 pM PIM1, 50 pM PIM2, or 55 pM PIM3, 1 μM FAM-peptide, and 10 μM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 μL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000® (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of −500V, an upstream voltage of −2150V, and a screening pressure of −1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm.
Measurement: Ki = 1.85 nM (pChEMBL 8.729999542236328)
Descriptors: MW 529.57, ALogP 2.99, HBA 9, HBD 2, PSA 129.2, QED 0.49
Compound (SMILES): Cn1ncc(NC(=O)c2csc(-c3cccc(Cl)c3F)n2)c1[C@@H]1CC[C@@H](N)[C@H](F)CO1
InChIKey: LJWZDMYZHCYQGJ-IOASZLSFSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: PIM Kinase Binding Assay: LC3K assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO. PIM reactions were carried out in a final volume of 10 μL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 μL 2×ATP and test compound to 5 μL of 2× enzyme and FAM-peptide, contained 20 pM PIM1, 50 pM PIM2, or 55 pM PIM3, 1 μM FAM-peptide, and 10 μM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 μL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000® (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of −500V, an upstream voltage of −2150V, and a screening pressure of −1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm.
Measurement: Ki = 0.054 nM (pChEMBL 10.270000457763672)
Descriptors: MW 467.93, ALogP 4.11, HBA 7, HBD 2, PSA 95.06, QED 0.6
Compound (SMILES): CCC(=O)N(C)[C@H]1CC[C@@H](C(=O)N2CC[C@@]3(C)c4cccc(O)c4C[C@@H]2C3(C)C)CC1
InChIKey: GHHULKUVNUQNMO-DGYXAIABSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Homogeneous Time-Resolved Fluorescence (HTRF): In vitro inhibition of 11beta -HSD1 by test compounds was determined with HTRF (Homogeneous Time-Resolved Fluorescence) technology (cisbio international, France) detecting cortisol generated from cortisterone by human liver microsomes. Briefly, compounds were incubated for 1 hour at 37 C. in Tris buffer (20 mM tris, 5 mM EDTA, pH 6.0) containing NADPH (200 uM) and cortisone (80 nM). Cortisol generated in the reaction is then detected with a competitive immunoassay, involving two HTRF conjugates: cortisol linked to XL665 and anti-cortisol antibody labeled with Europium cryptate. The incubation period for detection reaction was typically 2 hours. The amount of cortisol is determined by reading the time-resolved fluorescence of the wells (Ex 320/75 nm; Em 615/8.5 nm and 665/7.5 nm). The ratio of the two emission signals is then calculated (Em665*10000/Em615).
Measurement: IC50 = 695 nM (pChEMBL 6.159999847412109)
Descriptors: MW 426.6, ALogP 4.26, HBA 3, HBD 1, PSA 60.85, QED 0.79
Compound (SMILES): COc1ccc(C2=C[C@@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)NC(=O)C2(F)C#N)cc1
InChIKey: BHSJXNNODPQRCT-FOIFJWKZSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: MGAT LCMS Assay: The MGAT enzyme reactions were performed in CORNING Falcon 96-well Polypropylene plates, in a total volume of 60 uL of 50 mM Potassium Phosphate buffer pH 7.4, containing a final concentration of 100 uM 2-oleoylglycerol, 15 uM oleoyl-Coenzyme A and 0.0013 ug/uL Human or Mouse MGAT-2 or 0.0026 ug/uL Rat recombinant MGAT-2 membranes expressed in Sf9 cells. Assay plates were run through a fully automated robotics system and shaken for 5 seconds every minute for a total 10 minutes. The reactions were then quenched with 120 uL of ice cold methanol containing 1 ug/mL 1,2-distearoyl-rac-glycerol as the internal standard. Plates were shaken for 2 minutes and spun down to remove protein precipitation. After the spin, samples were transferred to LC/MS compatible PCR plates. For LC/MS analysis, a ThermoFisher Surveyor pump, utilizing a Waters Symmetry C8, 50x2.1 mm column, was used for the chromatography of enzyme products.
Measurement: IC50 = 756 nM (pChEMBL 6.119999885559082)
Descriptors: MW 516.41, ALogP 5.62, HBA 4, HBD 1, PSA 71.35, QED 0.38
Compound (SMILES): N#Cc1ccc(-c2cc(C(=O)Nc3ccc(OC(F)(F)F)cc3)cnc2N2CC[C@@H](O)C2)[nH]1
InChIKey: SJHGRVSGRQFAEW-MRXNPFEDSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Radiometric Filter-Binding Assay: The assay was performed by mixing 10 μL of the compound pre-diluted with 10 μL of ATP (20 μM ATP with 0.1 μCi [γ-33P]-ATP) with the phospho-acceptor peptide poly[Ala6Glu2LysHBr5Tyr1]=polyAEKY) in 20 mM Tris/HCl pH 7.5, 1 mM DTT, 10 mM MgCl2, 0.01 mM Na3VO4, 50 mM NaCl. 10 μL of enzyme (ranging between 5 nM to 20 nM) was added to initiate the reaction. Pre-incubation of enzyme with compounds (when stated) was performed by exposing the enzyme to compounds prior to addition of the substrate mixture (ATP and/or peptide substrate). After 15 min at room temperature, the reaction was stopped by the addition of 50 μL 125 mM EDTA, and the peptide-bound 33P separated on filter-plates (PVDF or MAIP; Millipore, Volketswil, Switzerland) prepared according to the manufacturer's instructions. Filter-plates were washed 3× with 0.5% H3PO4, followed by addition of 30 μL scintillation cocktail (Microscint, Perkin Elmer) per well and then analysed in a TopCount NXT scintillation counter (Perkin Elmer).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 457.41, ALogP 3.67, HBA 6, HBD 3, PSA 114.27, QED 0.54
Compound (SMILES): O=c1[nH]c(N2CCOCC2)nc(N[C@@H]2CCCNC2)c1-c1csc(-c2ccccc2)n1
InChIKey: GDXKJYBYUSVTHJ-MRXNPFEDSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: IMAP technology (Molecular Devices): A 20 ul reaction mixture contains 10 mM TriHCl, pH 7.2, 0.5 nM GST tagged IRAK4 (SignalChem), 100 nM fluorescent peptide substrate (RP7030, Molecular Devices), 100 uM ATP, 1 mM DTT, 1 mM MgCl2, and 0.01% Tween 20. The reaction is initiated by the addition of ATP. After incubation for 30 minutes at 25° C., 60 ul of Progressive IMAP Reagent (Molecular Devices) is added to stop the reaction. Change in RP7030's FP is determined by a FP reader (Analyst HT, LJL BioSystems).
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 438.56, ALogP 2.56, HBA 8, HBD 3, PSA 95.17, QED 0.56
Compound (SMILES): Cc1cc(C[C@@H]2C[C@H](c3cccc(Cl)c3)[C@@H](c3ccc(Cl)cc3)N(CC3CC3)C2=O)no1
InChIKey: BASWMXRPLQGFOW-NIJXNBFTSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Homogenous Time-Resolved Fluorescence Assay (HTRF1 Assay): The standard assay conditions for the in vitro HTRF assay consisted of a 50 ul total reaction volume in black 384-well Costar polypropylene plates in 1xPBS buffer pH 7.4, 1 mM DTT, 0.1% BSA, 2.5 nM GST-hMDM2 (aa 1-188), 5 nM biotinylated-p53 (aa 1-83), 1.8 nM SA-XLent (Cisbio; Bedford, Mass.), 0.6 nM anti-GST cryptate monoclonal antibody (Cisbio; Bedford, Mass.) and 200 mM KF. Amino acid residues 1-188 of human MDM2 were expressed as an amino-terminal glutathione-S-transferase (GST) fusion protein (GST-hMDM2) in Escherichia coli. Residues 1-83 of human p53 were expressed as an amino-terminal AviTag-TrxA-6-His fusion protein (biotinylated p53) in E. coli. Each protein was purified from cell paste by affinity chromatography.Specifically, 10 uL of GST-hMDM2 was incubated with 10 ul of diluted compound (various concentrations, serially diluted) in 10% DMSO for 20 minutes at room temperature. 20 uL of biotinylated-p53 was added to the GST-hMDM2+compound mixture, and then incubated at room temperature for 60 min. 10 uL of detection buffer consisting of SA-XLent, anti-GST cryptate antibody and KF was added to GST-hMDM2, biotinylated-p53 and compound reaction and left at room temperature to reach equilibrium for >4 hrs. The final concentration of DMSO in the reaction was 2%. Time-resolved fluorescence readings were measured on a microplate multilabel reader. Percentage of inhibition was calculated relative to nutlin-3.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 469.41, ALogP 6.62, HBA 3, HBD 0, PSA 46.34, QED 0.41
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@H](c1ccc([C@@H](CO)N(CCC(C)(C)C)S(=O)(=O)c2ccc3[nH]ncc3c2)s1)C(F)(F)F)C(c1ccccc1)c1ccccc1
InChIKey: XQVRBQCDTOFNAM-IUXHJFJISA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Inhibition Assay: The inhibition of WT HIV-1 protease was studied using the reaction of the protease (expressed in Eschericia coli) with a peptide substrate [Val-Ser-Gln-Asn-(betanaphthyl)Ala-Pro-Ile-Val (SEQ ID NO:1)]. Compounds were tested using Procedure A. In Procedure A, the test compound was first preincubated with the enzyme in assay buffer (50 mM sodium acetate, pH 5.5, 100 mM NaCl, and 0.1% BSA) for 30 minutes at room temperature. Substrate was then added to 400 micromolar in a total volume of 80 microliters containing 10 picomolar HIV-1 protease and the reaction was incubated for 1 hour at 30° C. The reaction was quenched with the addition of 120 microliters of 10% phosphoric acid. The product formation was determined after separation of product and substrate on a Zorbax Eclipse XDB-C18 column (Agilent Technologies, Santa Clara, Calif.) connected to an Agilent 1100 high performance liquid chromatography system with fluorescence detection (excitation 270 nanometer and emission 330 nanometer).
Measurement: IC50 = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 785.91, ALogP 7.06, HBA 8, HBD 4, PSA 153.72, QED 0.09
Compound (SMILES): COc1cc(-c2nc(-c3ccnc(C)c3)c3n2C[C@@H](CF)OCC3)ccc1C
InChIKey: DSRMEQSMACBSIR-GOSISDBHSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: [35S]GTPgammaS Binding Assay: The frozen cell membrane fraction prepared as described above was thawed before use, and the resultant was diluted with a buffer for a binding assay (final concentrations: 20 mM HEPES, 100 mM NaCl, 1 mM MgCl2, 3 uM GDP, 300 ug/mL saponin, 0.1% BSA). The compound of each example was added to a cell membrane fraction containing 1.8 to 3 ug/assay of membrane protein on a plate, followed by incubation at room temperature for 30 minutes. Thereafter, with glutamic acid (in a final concentration of 10 uM) added thereto, incubation was performed at room temperature for 15 minutes, and thereafter, [35S]GTPγS (in a final concentration of 0.8 kBq) and 588 ug WGA-SPA beads were added thereto, followed by incubation at room temperature for 1 hour. After the incubation, the plate was subjected to the centrifugal separation at 2,500 rpm and room temperature, and then, membrane cell binding radioactivity was measured with a top count. A [35S]GTPγS binding amount obtained in the presence of glutamic acid was defined as specific binding. On the basis of ratios of inhibiting the specific binding at various concentrations of the compounds of the respective examples, inhibition curves were obtained. Concentrations of the compounds of the respective examples at which the specific [35S]GTPγS binding amount was suppressed by 50% (IC50 values) were calculated on the basis of the inhibition curves.
Measurement: IC50 = 29.4 nM (pChEMBL 7.53000020980835)
Descriptors: MW 381.45, ALogP 4.15, HBA 5, HBD 0, PSA 49.17, QED 0.68
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(N2CC[C@@H](O)C2)c(-c2ccc(C(F)(F)F)nc2)c1
InChIKey: FGMQZTUTUMIVRQ-MRXNPFEDSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Radio ABL1 (64-515) Assay: For determination of ABL kinase activity, the radiometric filter-binding assay was used. The assay was performed by mixing 10 uL of the compound pre-diluted with 10 uL of ATP (20 uM ATP with 0.1 uCi [γ-33P]-ATP) with the phospho-acceptor peptide poly[Ala6Glu2LysHBr5Tyr1]=polyAEKY) in 20 mM Tris/HCl pH 7.5, 1 mM DTT, 10 mM MgCl2, 0.01 mM Na3VO4, 50 mM NaCl. 10 uL of enzyme (ranging between 5 nM to 20 nM) was added to initiate the reaction. Pre-incubation of enzyme with compounds (when stated) was performed by exposing the enzyme to compounds prior to addition of the substrate mixture (ATP and/or peptide substrate). After 15 mM at room temperature, the reaction was stopped by the addition of 50 uL 125 mM EDTA, and the peptide-bound 33P separated on filter-plates (PVDF or MAIP; Millipore, Volketswil, Switzerland) prepared according to the manufacturer's instructions. Filter-plates were washed 3x with 0.5% H3PO4, followed by addition of 30 uL scintillation cocktail (Microscint, Perkin Elmer) per well and then analysed in a TopCount NXT scintillation counter (Perkin Elmer).
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 512.41, ALogP 4.88, HBA 6, HBD 2, PSA 87.58, QED 0.47
Compound (SMILES): c1ccc(OC[C@H]2CN(CCN3CCc4ccccc43)CCO2)nc1
InChIKey: DSTWBFPFQZUGGQ-GOSISDBHSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Mus musculus
UniProt: Q64264
Assay: Radioligand Binding Assay: The detailed experimental protocols for the radioligand and functional receptor assays are available on the NIMH PDSP website at http://pdsp.med.unc.edu/UNC-CH %20Protocol %20Book.pdf. A. Serotonin receptors: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT6 and 5-HT7. Assay Buffer: Standard Binding Buffer (50 mM Tris-HCl, 10 mM MgCl2, 1 mM EDTA, pH 7.4) Membrane Fraction Source: Transiently or stably transfected cell lines (e.g., HEK293, COS, CHO, NIH3T3). Protocol adapted from Roth et al. (1986), J. Pharmacol. Exp. Ther., 238(2): 480-485; and Roth et al. (1994), J. Pharmacol. Exp. Ther., 268(3): 1403-1410. Adrenergic Receptors: alpha1A, alpha1B, alpha2A, alpha2B, alpha2C, beta1, beta2, beta3 Assay Buffers: For alpha1 receptors, alpha1 Binding Buffer (20 mM Tris-HCl, 145 mM NaCl, pH 7.4); for alpha2 receptors, alpha2 Binding Buffer (50 mM Tris-HCl, 5 mM MgCl2, pH 7.7); for beta receptors.
Measurement: Ki = 2883 nM (pChEMBL 5.539999961853027)
Descriptors: MW 339.44, ALogP 2.22, HBA 5, HBD 0, PSA 37.83, QED 0.81
Compound (SMILES): Cc1nccc(-c2ccc(C[C@H](NC(=O)[C@@H]3Cc4cc5c(cc4CN3C(=O)N[C@H](C)c3ccccc3)O[C@@H](c3ccc(OCCc4ccc(Cl)cc4)cc3)CO5)C(=O)O)cc2)c1C
InChIKey: KRJSNKJYELEHEL-PAEUQOBWSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: cAMP Functional Assay: The efficacy of GLP-1 receptor agonists was studied in a cAMP functional assay using HEK-293 Cells expressing the cloned human GLP-1 receptor. GLP-1-expressing cells (10,000-20,000 cells per 0.1 mL) were plated in 96-well plates in Dulbecco's modified eagles media (DMEM) containing 10% fetal bovine serum, 2 mg/mL G418 and penicillin-streptomycin. Following overnight incubation of cells, media was removed, and compounds (at concentrations ranging from 0.0001 to 100 μM) were added to monolayer cells in Iscove's modified dulbecco's medium (IMDM), 100 μM RO 20-1724 PDE inhibitor, 0.1% BSA, 2% DMSO in a final volume of 100 μL, and incubated for 30 min at 37° C. 95%02, 5% CO2 in a humidified incubator. Alternatively, cells were harvested and combined with compounds in suspension using the buffer and protocol described above. cAMP was quantified using a homogenous time-resolved fluorescence detection system (cAMP dynamic, CIS bio International).
Measurement: EC50 = 179 nM (pChEMBL 6.75)
Descriptors: MW 865.43, ALogP 9.16, HBA 7, HBD 3, PSA 139.32, QED 0.1
Compound (SMILES): CS(=O)(=O)N[C@@H]1CCCN(c2nc(C(N)=O)c(Nc3ccccn3)s2)C1
InChIKey: YGFCENSHEQSPLT-SNVBAGLBSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: TR-FRET (Time Resolved FRET) Assay: This BTK competition assay measures compound potency (IC50) for the inactivated state of Bruton's Tyrosine Kinase using FRET (Forster/Fluorescence Resonance Energy Transfer) technology. The BTK-Eu complex was incubated on ice one hour prior to use at a starting concentration of 50 nM BTK-Bioease™: 10 nM Eu-streptavidin (Perkin-Elmer Catalog# AD0062). The assay buffer consisted of 20 mM HEPES (pH 7.15), 0.1 mM DTT, 10 mM MgCl2, 0.5 mg/ml BSA with 3% Kinase Stabilizer (Fremont Biosolutions, Catalog # STB-K02). After 1 h, the reaction mixture from above was diluted 10 fold in assay buffer to make 5 nM BTK: 1 nM Eu-Streptavidin complex (donor fluorophore). 18 μl of a mixture of 0.11 nM BTK-Eu and 0.11 nM Kinase Tracer 178 (Invitrogen, Catalog # PV5593,) with BTK-Eu alone as no negative control, was then dispensed into 384-well flat bottom plates (Greiner, 784076). Compounds to be tested in assay were prepared as 10× concentrations and serial dilution in half-log increments was performed in DMSO so as to generate 10 point curves. To initiate the FRET reaction, compounds prepared as 10× stock in DMSO was added to the plates and the plates were incubated 18-24 h at 14° C. After the incubation the plates were read on a BMG Pherastar Fluorescent plate reader (or equivalent) and used to measure the emission energy from the europium donor fluorophore (620 nm emission) and the FRET (665 nm emission).
Measurement: IC50 = 5065.1 nM (pChEMBL 5.289999961853027)
Descriptors: MW 396.5, ALogP 0.9, HBA 8, HBD 3, PSA 130.31, QED 0.66
Compound (SMILES): Cc1ccc([C@H]2C[C@@H]2COc2nc(C)ncc2-c2nn(C)c(=O)cc2C)nc1
InChIKey: MKQLWQRZNTXJFZ-CVEARBPZSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: PDE10 Fluorescence Polarization (FP) Assay: The fluorescence polarization assay for cyclic nucleotide phosphodiesterases was performed using an IMAP FP kit supplied by Molecular Devices, Sunnyvale, Calif. (product # R8139). IMAPU technology has been applied previously to phosphodiesterase assays (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). Assays were performed at room temperature in 384-well microtiter plates with an incubation volume of 20.2 uL. Solutions of test compounds were prepared in DMSO and serially diluted with DMSO to yield 8 uL of each of 10 solutions differing by 3-fold in concentration, at 32 serial dilutions per plate.
Measurement: Ki = 9.683 nM (pChEMBL 8.010000228881836)
Descriptors: MW 377.45, ALogP 2.74, HBA 7, HBD 0, PSA 82.79, QED 0.68
Compound (SMILES): OC[C@@H](O)c1nc(-c2ccc(Oc3ccc(F)cc3)cc2)c2ccccc2n1
InChIKey: ZOMXULDFQVDHIF-HXUWFJFHSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FLIPR Assay: The assay buffer was formulated by removing 120 mL from a 1 L bottle of fresh, sterile dH2O (Mediatech, Herndon, Va.) and adding 100 mL of 10xHBSS that does not contain Ca++ or Mg++ (Gibco, Invitrogen, Grand Island, N.Y.) followed by 20 mL of 1.0 M Hepes, pH 7.3 (Fisher Scientific, BP299-100). The final buffer consisted of 20 mM Hepes, pH 7.3, 1.261 mM CaCl2, 0.493 mM MgCl2, 0.407 mM Mg(SO)4, 5.33 mM KCl, 0.441 mM KH2PO4, 137 mM NaCl, 0.336 mM Na2HPO4 and 0.556 mM D-glucose (flanks et al., Proc. Soc. Exp. Biol. Med. 71:196 (1949)), and the simple formulation was typically the basic buffer throughout the assay (i.e., all wash and addition steps).
Measurement: IC50 = 849 nM (pChEMBL 6.070000171661377)
Descriptors: MW 376.39, ALogP 4.25, HBA 5, HBD 2, PSA 75.47, QED 0.54
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(N2CC[C@@H](O)C2)c(-c2cccc(CO)c2)c1
InChIKey: TXPXPQQJSTYTNG-LJQANCHMSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Radio ABL1 (64-515) Assay: For determination of ABL kinase activity, the radiometric filter-binding assay was used. The assay was performed by mixing 10 uL of the compound pre-diluted with 10 uL of ATP (20 uM ATP with 0.1 uCi [γ-33P]-ATP) with the phospho-acceptor peptide poly[Ala6Glu2LysHBr5Tyr1]=polyAEKY) in 20 mM Tris/HCl pH 7.5, 1 mM DTT, 10 mM MgCl2, 0.01 mM Na3VO4, 50 mM NaCl. 10 uL of enzyme (ranging between 5 nM to 20 nM) was added to initiate the reaction. Pre-incubation of enzyme with compounds (when stated) was performed by exposing the enzyme to compounds prior to addition of the substrate mixture (ATP and/or peptide substrate). After 15 mM at room temperature, the reaction was stopped by the addition of 50 uL 125 mM EDTA, and the peptide-bound 33P separated on filter-plates (PVDF or MAIP; Millipore, Volketswil, Switzerland) prepared according to the manufacturer's instructions. Filter-plates were washed 3x with 0.5% H3PO4, followed by addition of 30 uL scintillation cocktail (Microscint, Perkin Elmer) per well and then analysed in a TopCount NXT scintillation counter (Perkin Elmer).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 473.45, ALogP 3.96, HBA 6, HBD 3, PSA 94.92, QED 0.5
Compound (SMILES): COC(=O)[C@H]1CCCN1C(=O)c1cc(C(=O)N[C@@H](c2ccc(F)cc2)C(C)C)n2c1COCC2
InChIKey: OUDMNRXDROKPJS-DENIHFKCSA-N
Target: Potassium channel subfamily K member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14649
Assay: TASK-1 Inhibiition Assay: Human TASK-1 channels were expressed in Xenopus oocytes. For this purpose, oocytes were isolated from Xenopus laevis and defoliculated. Subsequently, TASK-1-encoding RNA synthesized in vitro was injected into the oocytes. After two days of TASK-1 protein expression, TASK-1 currents were measured by two-microelectrode voltage clamp. Data were acquired and analyzed using a TEC-10cx amplifier (NPI Electronic, Tamm, Germany) connected to an ITC-16 interface (Instrutech Corp., Long Island, USA) and Pulse software (HEKA Elektronik, Lambrecht, Germany). Oocytes were clamped to -90 mV and TASK-1 mediated currents were measured during 500 ms voltage pulses to 40 mV. Oocytes were continuously superfused with ND96 buffer containing 96 mM sodium chloride, 2 mM potassium chloride, 1.8 mM calcium chloride, 1 mM magnesium chloride, 5 mM 4-(2-hydroxyethyl)-piperazine-1-ethanesulfonic acid (HEPES; pH adjusted to 7.4 with sodium hydroxide). All experiments were performed at room temperature.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 471.53, ALogP 3.06, HBA 6, HBD 1, PSA 89.87, QED 0.65
Compound (SMILES): CC(C)(O)[C@H](F)CNC(=O)c1cnc(-n2ncc3cc(C#N)cnc32)cc1NCC(F)(F)F
InChIKey: GSPQMNLLHHKGRT-OAHLLOKOSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 L prepared from 15 L additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.2, 10 mM MgCl2, 0.015% Brij 35 and 4 mM DTT). The reaction was initiated by the combination of IRAK4 with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 min. and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentrations of reagents in the assays are ATP, 500 μM; FL-IPTSPITTTYFFFKKK peptide 1.5 μM; IRAK4, 0.6 nM; and DMSO, 1.6%.
Measurement: IC50 = 11.9 nM (pChEMBL 7.920000076293945)
Descriptors: MW 465.41, ALogP 2.5, HBA 8, HBD 3, PSA 128.75, QED 0.46
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2cc(-c3ccncc3)on2)C1
InChIKey: ZXSWQIGDJADBQU-LLVKDONJSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl.Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 283.29, ALogP 1.02, HBA 6, HBD 1, PSA 95.05, QED 0.84
Compound (SMILES): C#CCN1CCC(/C=C\c2ccc(C#N)cc2)CC1
InChIKey: CMMBAZNRQYFLFC-ARJAWSKDSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human microsomal MAOB expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 15 mins followed by substrate addition and measured over 20 mins by amplex red reagent-based horseradish peroxidase-coupled fluorometric assay
Measurement: IC50 = 1745.3 nM (pChEMBL 5.760000228881836)
Descriptors: MW 250.35, ALogP 2.92, HBA 2, HBD 0, PSA 27.03, QED 0.77
Compound (SMILES): COc1ncc(-c2cccc(N3CCN(c4cnc(N)nc4N)CC3)c2)cn1
InChIKey: GUZBZPCNAJDYMO-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of human DHFR expressed in Escherichia coli BL21 competent cells using DHF as substrate preincubated for 15 mins followed by substrate and NADPH addition and measured after 60 mins by resazurin dye based diaphorase-coupled assay
Measurement: IC50 = 308 nM (pChEMBL 6.510000228881836)
Descriptors: MW 378.44, ALogP 1.43, HBA 9, HBD 2, PSA 119.31, QED 0.69
Compound (SMILES): O=C(NCCN1CCCCC1)c1ccc(OC2CCN(C3CCC3)CC2)cc1.O=C(O)[C@H](O)[C@@H](O)C(=O)O
InChIKey: KAJCHRWKXYJNCC-LREBCSMRSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3]-RAMH from recombinant human histamine H3 receptor expressed in CHO-K1 cell membranes after 60 mins by scintillation counting
Measurement: Ki = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 385.55, ALogP 3.3, HBA 4, HBD 1, PSA 44.81, QED 0.78
Compound (SMILES): CCN(CC)CCCNc1nc(/C=C/c2ccc(C(C)C)cc2)nc2ccc(Cl)cc12
InChIKey: FSQXNAHEBFNFAZ-XNTDXEJSSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin) using TAMRA-Src-tide as substrate measured after 1 hr in presence of ATP at its Km concentration by IMAP-FP assay
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 437.03, ALogP 6.72, HBA 4, HBD 1, PSA 41.05, QED 0.36
Compound (SMILES): Clc1cc(NC2CCOCC2)c2ncc(-c3ccc4[nH]ncc4c3)n2n1
InChIKey: CLMCEBACAXFRMA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of dephosphorylated IRE1alpha (G547 to L977 residues) (unknown origin) -dependent cleavage of FAM-labeled stem-loop RNA containing the XBP1 cleavage site preincubated for 30 mins followed by RNA XBP1 substrate addition and measured after 15 mins by FRET assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 368.83, ALogP 3.52, HBA 6, HBD 2, PSA 80.13, QED 0.58
Compound (SMILES): CC1(C)O[C@H]2O[C@H](CNCCCCn3c(-c4ccccc4)nc(-c4ccccc4)c3-c3ccccc3)[C@H](O)[C@H]2O1
InChIKey: CPAWJRGSKSVSMA-KHHZTBOTSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: P21836
Assay: Inhibition of AChE in Swiss mouse brain using acetylthiocholine iodide as substrate incubated for 10 mins followed by substrate addition and measured after 10 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 539.68, ALogP 5.49, HBA 7, HBD 2, PSA 77.77, QED 0.26
Compound (SMILES): CN1Cc2cc(NC(=O)c3cnn4cccnc34)c(N3CCOCC3)cc2C1=O
InChIKey: VFBUHDWSAHILTP-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full-length N-terminal His6-tagged human IRAK4 expressed in baculovirus expression system using H-KKARFSRFAGSSPSQSSMVAR peptide as substrate after 90 mins by fluorescence polarisation assay
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 392.42, ALogP 1.4, HBA 7, HBD 1, PSA 92.07, QED 0.72
Compound (SMILES): Cl.Nc1nc(N)c(-c2cccc(Cl)c2)c(COc2cccc(OCCCC(=O)O)c2)n1
InChIKey: HTFSJBQCOYERLA-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of human dihydrofolate reductase using dihydrofolate as substrate in presence of NADPH by UV-vis spectrophotometry analysis
Measurement: Ki = 74.16 nM (pChEMBL 7.130000114440918)
Descriptors: MW 428.88, ALogP 3.78, HBA 7, HBD 3, PSA 133.58, QED 0.44
Compound (SMILES): CCOC(=O)CCCCCCOc1cc2oc3cc4c(c(O)c3c(=O)c2c(CC=C(C)C)c1OC)C=CC(C)(C)O4
InChIKey: GGEKMXWCBAWKNU-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of human PDE4D2 (86 to 413 residues) expressed in Escherichia coli BL21 codon-plus cells using [3H]cAMP as substrate incubated for 15 mins by liquid scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 564.68, ALogP 7.25, HBA 8, HBD 1, PSA 104.43, QED 0.11
Compound (SMILES): CCC(CC)CN(CCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)C(=O)CO
InChIKey: VTPKDSOSROLKKH-KOUNCHBCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-DPN from guinea pig kappa opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 0.1259 nM (pChEMBL 9.899999618530273)
Descriptors: MW 415.58, ALogP 2.75, HBA 4, HBD 2, PSA 86.87, QED 0.62
Compound (SMILES): O=C(NC(=S)Nc1cc([N+](=O)[O-])ccc1O)c1ccccc1
InChIKey: HJPFGQQNQIEPHT-UHFFFAOYSA-N
Target: Fructose-bisphosphate aldolase class 2 (SINGLE PROTEIN), Synechocystis sp. (strain PCC 6803 / Kazusa)
UniProt: Q55664
Assay: Inhibition of recombinant Synechocystis sp. PCC 6803 FBA2 expressed in Escherichia coli BL21 (DE3) using FBP as substrate measured over 5 mins
Measurement: Ki = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 317.33, ALogP 2.43, HBA 5, HBD 3, PSA 104.5, QED 0.35
Compound (SMILES): COc1ccc(/C=C(\C)C(=O)c2cc(OC)c(OC)c(OC)c2)cc1OCCCCCCCC(=O)NO
InChIKey: NDWVAHMCNHGVBK-XDJHFCHBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 15.2 nM (pChEMBL 7.820000171661377)
Descriptors: MW 515.6, ALogP 5.23, HBA 8, HBD 2, PSA 112.55, QED 0.1
Compound (SMILES): COc1cc(OC)c(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1CC=C(C)C
InChIKey: HSFXRTBLDWBKAW-GXDHUFHOSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp-mediated multidrug resistance in human MCF7/Dox cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 12.5 uM after 48 hrs by MTT assay (Rvb = 51.19 +/- 0.95 microM)
Measurement: IC50 = 17410 nM (pChEMBL 4.760000228881836)
Descriptors: MW 395.5, ALogP 4.88, HBA 5, HBD 1, PSA 59, QED 0.39
Compound (SMILES): c1ccc(COc2cccc(-c3cn(C4CN5CCC4CC5)nn3)c2)cc1
InChIKey: VJEPFPRUUZASOL-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]epibatidine from human alpha4beta2 nAChR transfected in HEK293 cell membranes after 120 mins by liquid scintillation counting
Measurement: Ki = 668 nM (pChEMBL 6.170000076293945)
Descriptors: MW 360.46, ALogP 3.79, HBA 5, HBD 0, PSA 43.18, QED 0.69
Compound (SMILES): Cl.Cn1cc2c(nc(NCCCCCN)n3nc(-c4ccco4)nc23)n1
InChIKey: MXJCRFLTIIYAHA-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]-CCPA from human adenosine A1 receptor expressed in CHO cells by radioligand competition analysis
Measurement: Ki = 778 nM (pChEMBL 6.110000133514404)
Descriptors: MW 340.39, ALogP 1.81, HBA 9, HBD 2, PSA 112.09, QED 0.49
Compound (SMILES): Cl.Cl.Cl.O=C(NCc1cccnn1)c1csc(CCNCCc2nc3ccccc3[nH]2)n1
InChIKey: FLPDAOUYYFILCP-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as induction of ferroportin internalization and degradation incubated overnight by FACS assay
Measurement: EC50 = 3015 nM (pChEMBL 5.519999980926514)
Descriptors: MW 407.5, ALogP 2.11, HBA 7, HBD 3, PSA 108.48, QED 0.37
Compound (SMILES): Nc1ccccc1-n1cc(-c2ccc(C(=O)O)cc2)nn1
InChIKey: HWTUOLQHJYZYDN-UHFFFAOYSA-N
Target: ORF 73 (SINGLE PROTEIN), Human herpesvirus 8
UniProt: O40947
Assay: Inhibition of fluorescent labelled LBS1 DNA binding to human herpesvirus 8 C-terminal His-tagged LANA oligomerization deficient mutant DBD (1008 to 1146 residues) expressed in Escherichia coli BL21 (DE3) preincubated for 60 mins followed by fluorescent labelled LBS2 addition and measured after 90 mins by fluorescence polarization assay
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 280.29, ALogP 2.21, HBA 5, HBD 2, PSA 94.03, QED 0.72
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)c2cccc(c2)-c2cccc3c(c[nH]c23)C[C@@H](C(N)=O)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC1=O
InChIKey: JUVWMVYEUFVLOP-ZXYZSCNASA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of human vitronectin binding to human integrin alphavbeta3 receptor after 1 hr by ELISA
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 780.84, ALogP -0.47, HBA 8, HBD 11, PSA 303.58, QED 0.06
Compound (SMILES): c1ccc(N2CCN=C2c2ccc(C3=NCCN3c3ccccc3)cc2)cc1
InChIKey: KYODUKMDIQJBCW-UHFFFAOYSA-N
Target: Polymerase acidic protein (SINGLE PROTEIN), Influenza A virus (A/Puerto Rico/8/1934(H1N1))
UniProt: P03433
Assay: Inhibition of Influenza A virus (A/Puerto Rico/8/34(H1N1)) PA endonuclease infected in MDCK cells assessed as reduction in virus titer treated with cells for 1 hr prior to viral infection for 1 hr followed by compound washout and subsequent compound addition measured after 48 hrs by hemagglutination test
Measurement: IC50 = 77000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 366.47, ALogP 4.22, HBA 4, HBD 0, PSA 31.2, QED 0.69
Compound (SMILES): CNC(=O)Nc1cc(Oc2c(F)cccc2F)ccn1
InChIKey: QUSPGQBMMOFJNY-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of human recombinant glucokinase using 5 mM glucose monitored over 5 mins in presence of NAD+ by glucose 6-phosphate dehydrogenase coupled assay
Measurement: EC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 279.25, ALogP 2.9, HBA 3, HBD 2, PSA 63.25, QED 0.91
Compound (SMILES): Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)nc(NCC3(N)COC3)c2c1
InChIKey: GAAICKUTDBZCMT-UHFFFAOYSA-N
Target: Fusion glycoprotein F0 (SINGLE PROTEIN), Human respiratory syncytial virus A (strain A2)
UniProt: P03420
Assay: Inhibition of Human respiratory syncytial virus Fusion protein D486N mutant expressed in Hep2 cells as reduction in virus induced cytopathic effect by CCK-8 assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 439.54, ALogP 1.87, HBA 8, HBD 2, PSA 110.44, QED 0.63
Compound (SMILES): CCCCC[C@H](O)CC[C@H]1C(=O)C=C[C@@H]1C/C=C/CCCC(=O)O
InChIKey: ASJSFCMKCZVQDY-IHPGZOJESA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of P300 (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 336.47, ALogP 4.28, HBA 3, HBD 2, PSA 74.6, QED 0.39
Compound (SMILES): COc1cc(/C=C/C(=O)NO)ccc1OCCCNC(=O)c1ccccc1O
InChIKey: VIZRRSCMOZSAAT-CSKARUKUSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 386.4, ALogP 2.12, HBA 6, HBD 4, PSA 117.12, QED 0.23
Compound (SMILES): Nc1nc(C(=O)Nc2cc(-c3ccc(OCC4CCCNC4)nc3)ccc2Cl)co1
InChIKey: OMKCQAFXNZNGMG-UHFFFAOYSA-N
Target: Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (SINGLE PROTEIN), Homo sapiens
UniProt: P22234
Assay: Inhibition of wild type full length human PAICS using CAIR as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by ADP2 tracer-based fluorescence assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 427.89, ALogP 3.6, HBA 7, HBD 3, PSA 115.3, QED 0.55
Compound (SMILES): OB1Oc2ccc(O)cc2C=C1c1ccc(O)c(O)c1
InChIKey: YZUGZQGGNCOEBI-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of self-induced aggregation of amyloid beta (1 to 42) (unknown origin) after 48 hrs by thioflavin T-based fluorescence method
Measurement: IC50 = 17500 nM (pChEMBL 4.760000228881836)
Descriptors: MW 270.05
Compound (SMILES): Cl.NOC(c1ccccc1)c1cccc(Cl)c1Cl
InChIKey: LPWUOLCWLJCNRE-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin) using L-tryptophan as substrate by spectrophotometric method
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 268.14, ALogP 3.97, HBA 2, HBD 1, PSA 35.25, QED 0.85
Compound (SMILES): Cc1cc(N2CC(N)C2)nc(N)n1
InChIKey: NNRWOZRAHOUFDJ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]NAMH from human H3R expressed in HEK293T cells incubated for 2 hrs by microbeta scintillation counting analysis
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 179.23, ALogP -0.49, HBA 5, HBD 2, PSA 81.06, QED 0.61
Compound (SMILES): Cn1ccc2cc(C3CC(c4c(-c5ccccc5)c5cc(Cl)ccc5[nH]c4=O)=NN3C(=O)CCC(=O)O)ccc21
InChIKey: NOUQJRRABGAABZ-UHFFFAOYSA-N
Target: DNA repair protein RAD51 homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06609
Assay: Inhibition of biotinylated BRC4 peptide binding to His-tagged human RAD51 expressed in Escherichia coli Rosetta(DE3) pLysS cells assessed as BRC4-RAD51 protein -protein interaction by competitive ELISA
Measurement: EC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 553.02, ALogP 5.88, HBA 5, HBD 2, PSA 107.76, QED 0.27
Compound (SMILES): COc1cc(C(=O)NNS(=O)(=O)c2ccccc2F)cc(-c2ccccn2)c1
InChIKey: BPRHUJQGPQDKMZ-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 401.42, ALogP 2.52, HBA 5, HBD 2, PSA 97.39, QED 0.62
Compound (SMILES): CCCCNC(=O)c1cc(S(N)(=O)=O)c(Br)cc1SCCc1ccccc1
InChIKey: AUUAQVXOSSGYPF-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 471.44, ALogP 3.96, HBA 4, HBD 2, PSA 89.26, QED 0.43
Compound (SMILES): CC(C)N1N=C(C2CCCCC2)c2ccc(Cl)cc2N(c2ccc(CC3=NCCN3)cc2)C1=O
InChIKey: NPYKQNWNSLWPBX-UHFFFAOYSA-N
Target: Parathyroid hormone/parathyroid hormone-related peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q03431
Assay: Antagonist activity at human PTHR1 expressed in CHOK1 cells co-expressing Gs/Gq assessed as reduction in human PTH (1 to 34 residues)-induced cAMP accumulation incubated for 30 mins by HTRF assay
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 478.04, ALogP 6.15, HBA 4, HBD 1, PSA 60.3, QED 0.56
Compound (SMILES): CCC(=O)N(c1ccccc1)C1CCN(CC(F)c2ccccc2)CC1
InChIKey: VLXGGMZFUUJXRR-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from rat MOR stably extracted from HEK293 cell membranes incubated for 90 mins at pH 6.5 by liquid scintillation spectrophotometry
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 354.47, ALogP 4.6, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): COc1ccc(-c2cnc3[nH]cc(C#Cc4ccc(F)cc4)c3c2)cc1OC
InChIKey: HGIRXUUITBCEFW-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Displacement of tracer 222 from GST-tagged recombinant human AAK1 catalytic domain (1 to 510 amino acids) expressed in insect cells shaken for 30 secs and incubated for 1 hr by LanthaScreen Eu kinase binding assay
Measurement: IC50 = 387 nM (pChEMBL 6.409999847412109)
Descriptors: MW 372.4, ALogP 4.79, HBA 3, HBD 1, PSA 47.14, QED 0.53
Compound (SMILES): CCC(C)c1cc2c(N/N=C/c3nc(CNC)cs3)ncnc2s1
InChIKey: XVJGPSBOQZKQIQ-IFRROFPPSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/cyclin D1 (unknown origin) expressed in baculovirus infected Sf9 insect cells using GST-Rb as substrate in presence of [33P] ATP incubated for 30 mins
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 360.51, ALogP 3.83, HBA 8, HBD 2, PSA 75.09, QED 0.49
Compound (SMILES): COc1ncc(-c2ccc3cn[nH]c3c2)cc1NS(C)(=O)=O
InChIKey: NGHNUOBLVOFWKE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3KD (unknown origin) by HTRF assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 318.36, ALogP 2, HBA 5, HBD 2, PSA 96.97, QED 0.77
Compound (SMILES): Cc1cccc2c1C(=O)C1=C3CCCN3CCC1O2
InChIKey: OFYQSFDHNYPXAD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human erythrocyte BuChE using S-butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured every 30 secs for 1 hr by Ellman's method
Measurement: IC50 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 255.32, ALogP 2.69, HBA 3, HBD 0, PSA 29.54, QED 0.71
Compound (SMILES): CC(=O)OCCCOc1ccc(C2=N[C@]3(Cc4ccccc4)C(=O)N(CCS(=O)(=O)c4ccccc4)Cc4ccccc4[C@@H]3O2)cc1
InChIKey: VVMFLRARZHSLML-UNVMMQEESA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of Myc (unknown origin) expressed in HEK293T cells incubated for 16 hrs by firefly/renilla luciferase reporter gene assay
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 652.77, ALogP 5.33, HBA 8, HBD 0, PSA 111.57, QED 0.15
Compound (SMILES): CC(C)(C)c1cc2ccccc2n1Cc1ccc(C(=O)NO)cc1
InChIKey: YTLCVCCFNDIFMM-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of tubastatin-Alexa647-tracer binding to recombinant GST-tagged HDAC10 (unknown origin) measured after 1 hr by TR-FRET assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 322.41, ALogP 4.11, HBA 3, HBD 2, PSA 54.26, QED 0.56
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(OS(=O)(=O)O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: ROJMLIUODNIIEZ-PZENOAITSA-N
Target: Cholecystokinin receptor type A (SINGLE PROTEIN), Homo sapiens
UniProt: P32238
Assay: Displacement of [125I]-CCK-8 from human CCK1R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay
Measurement: IC50 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 1839.05