lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCN(CCNc2nc(-c3ccccc3)nc3c2nc(-c2ccccc2)c(=O)n3CCN2CCN(C)CC2)CC1
InChIKey: BDUVFMBQNZWZEI-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonism Assay: Day 1: A cell suspension of HEK-Blue™-hTLR9 cells at ~450,000 cells per ml in test medium which contained 5% (v/v) heat inactivated FBS was prepared. 180 μl of cell suspension (Ë¿80,000 cells) was added per well of a flat-bottom 96-well plate and place in an incubator at 37° C. for overnight. Day 2: Test compounds were serially diluted in test medium, generally starting at 10 μM, and diluting by 3 fold in a 96 well master plate. 20 μl of diluted test compound was transferred using a 12 channel multi-channel pipet to the cell plate and incubated at 37° C. for 1 hour. Then 20 μl of an hTLR9 agonist (such as ODN 2006, 1 μM) was added to each well and the plate incubated at 37° C. overnight. Day 3: Invivogen's QUANTI-Blue™ was prepared following the manufacturer's instructions. 180 ml of resuspended QUANTI-Blue™ was added per well of a flat bottom 96-well plate. 20 μl per well of induced HEK-Blue™-hTLR9 cells supernatant was then added to the plate and the plate was incubated at 37° C. for 1-3 h. SEAP levels were determined using a spectrophotometer at 620 nm.
Measurement: IC50 = 124 nM (pChEMBL 6.909999847412109)
Descriptors: MW 567.74, ALogP 2.43, HBA 10, HBD 1, PSA 85.66, QED 0.33
Compound (SMILES): CN(C)CCn1cc(NC(=O)c2ccc3cc4n(c3c2)CCCNC4=O)cn1
InChIKey: RMOMXCDBCHQPSZ-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Kinase Glo Plus Assay: Human RSK2 protein, purchased from Invitrogen, is used to measure kinase activity utilizing Kinase Glo Plus (Promega) a homogeneous assay technology, which uses a luciferin-luciferase based ATP detection reagent to quantify residual ATP. The assay is performed using 0.75 nM His-RSK2, 0.75 .mu.M ATP and 1.0 uM S6 Kinase/RSK Substrate Peptide 1 (Upstate, catalog #12-124), in assay buffer consisting of 25 mM HEPES, pH 7.5, 10 mM MgCl2, 5 mM MnCl2, 50 mM KCl, 0.2% BSA, 0.01% CHAPS, 100 uM Na3VO4, 0.5 mM DTT, and 1% DMSO. Solutions of test compounds at various concentrations are prepared by 1:3 fold serial dilution of a 1 mM solution of compound in DMSO. The DMSO solutions are further diluted with assay buffer to a final concentration of DMSO of 5%. The assay is performed in a 384 well, white, non-binding plate (Corning, catalogue #3574). Solutions of test compounds (10 uL) are transferred to a dry assay plate, followed by addition of 20 uL kinase.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 380.45, ALogP 1.79, HBA 6, HBD 2, PSA 84.19, QED 0.71
Compound (SMILES): COc1ccc(Nc2nc(Nc3ccc(OC)cc3)nc(NC(C)C)n2)cc1.Cl
InChIKey: VGPQJBNDABOROI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULD8
Assay: Inhibition of BEC1 (unknown origin) expressed in dihydrofolate reductase-deficient CHO cells assessed as decrease in KCl-induced intracellular 86Rb ion release after 20 mins
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 380.45, ALogP 4.2, HBA 8, HBD 3, PSA 93.22, QED 0.54
Compound (SMILES): CCN(C(=O)c1ccc(NC(=O)N2Cc3ccccc3C2)cc1)C(C)C
InChIKey: BKOHVHHKVMUBLH-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay : Probe 1:The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb-anti-His antibody (Invitrogen, Cat #PV5895), and 200 nM probe (Oregon Green 488-conjugated APO0866; A-1251667.0. Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
Measurement: IC50 = 1920 nM (pChEMBL 5.71999979019165)
Descriptors: MW 351.45, ALogP 4.1, HBA 2, HBD 1, PSA 52.65, QED 0.9
Compound (SMILES): CC[C@H](CN1CC[C@H](CNC(=O)c2ccc(Cl)cc2Cl)N[C@H](CNC(=N)N)C1=O)c1ccccc1
InChIKey: QAKJJRSICLFQDZ-ZWDAVXSWSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Radioligand Binding Assay: Assessments of compound binding to human MC5R (hMC5R)) by displacement of an 125I-labeled NDP-MSH receptor ligand peptide were performed essentially as described in the data sheets produced by Perkin Elmer to accompany their frozen hMC5R membranes (Perkin Elmer catalog number RBXMC5M400UA). [125I] NDP-MSH: Radiolabeled in House and Purified by HPLC: Na125I (0.5 mCi, 17.4 Ci/mg) was added to 50 μL sodium phosphate (50 mM, pH 7.4) in an eppendorf tube precoated with IODOGEN. After incubation for 10 mins the phosphate buffer containing the iodine was added to NDP-MSH (10 μl at 1 mg/mL) in a separate eppendorf tube. This was incubated for a further 10 mins. The iodinated NDP-MSH was purified by HPLC on a Zorbax SB 300 column using solvent A: 0.05% TFA and solvent B: 90% acetonitrile 0.045% TFA with a linear gradient, 0-67% B over 60 mins. The 125I NDP-MSH eluted at 52 mins after the unlabeled starting material (48 min) and was counted and stored in the freezer. It was used within 48 hrs, as radioactive decay and ligand decomposition resulted in greatly reduced specific binding observed after 72 hrs. Incubation buffer: 25 mM HEPES-KOH (pH 7.0), 1.5 mM CaCl2, 1 mM MgSO4, 0.1 M NaCl, 1 mM 1,10-phenanthroline, and 1 Complete™ protease inhibitor tablet/100 mL (Roche, catalog number 1873580). Perkin Elmer frozen hMC5 membranes: catalog number RBXMC5M400UA, 0.4 mL/vial; 400 microassays/vial, 0.78 mg/mL protein concentration. Vials of frozen membranes were thawed rapidly immediately before use, diluted with binding buffer and vortexed. Resuspended membranes were kept on ice until they were added to the wells of the plate. Assays were performed in 96 well polypropylene plates. Membranes (0.78 μg 40 μL of a 1:40 dilution in incubation buffer) were added to [125I] NDP-MSH (0.84 nM; 2200 Ci/mmol) and test compounds in a total volume of 140 μL. This was incubated for 1 hr at 37° C. Non-specific binding was determined with 3 mM NDP-MSH. Plates were filtered using a Tomtec cell harvester with GF/A filters (Wallac) (presoaked in 0.6% polyethylenimine) and washed three times with 1.0 mL ice-cold wash buffer (the above incubation buffer without 1,10-phenanthroline and Complete™ protease inhibitor tablet). The filters were dried in a 37° C. oven, placed in a sample bag and 5 mL Betaplatescint (Wallac) was added. Prepared filters were counted in cassettes in a Microbeta Trilux (Wallac) for 1 min.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 519.48, ALogP 2.96, HBA 4, HBD 5, PSA 123.34, QED 0.26
Compound (SMILES): COc1cc2c(c(OC)c1OC)C(=O)C1(OC)C=CC2C2C(=O)OC(=O)C21
InChIKey: BROAVPPFMVEBMD-UHFFFAOYSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9EPQ1
Assay: Antagonist activity at TLR1/2 in mouse RAW264.7 cells assessed as inhibition of Pam3CSK4-induced receptor activation by measuring NO production after 24 hrs
Measurement: IC50 = 74580 nM (pChEMBL 4.130000114440918)
Descriptors: MW 374.35, ALogP 1.26, HBA 8, HBD 0, PSA 97.36, QED 0.44
Compound (SMILES): COC(=O)Nc1nc2cc(C3(O)c4ccccc4C(=O)N3c3ccc(F)c(F)c3)ccc2[nH]1
InChIKey: ABUWAIFIVKCHQB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf (unknown origin) pre-incubated for 30 mins by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 450.4, ALogP 3.87, HBA 5, HBD 3, PSA 107.55, QED 0.44
Compound (SMILES): CCc1cc(CNc2nc(Nc3cc(C4CC4)n[nH]3)cc(N3CCN(C)CC3)n2)on1
InChIKey: UNZPRIBUQLQLQB-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human IGF1R kinase domain (M954 to C1367 residues) un-phosphorylated apo-enzyme form expressed in baculovirus based expression system using poly-EY peptide incubated for 2 hrs by luciferase-luciferin coupled chemiluminescent assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 423.53, ALogP 2.74, HBA 9, HBD 3, PSA 111.03, QED 0.5
Compound (SMILES): COc1ccccc1Oc1nc(NC2CC2)n2ncc(/C=C3\NC(=O)NC3=O)c2n1
InChIKey: SPWOYXDFAQZQLT-WQLSENKSSA-N
Target: Casein kinase II subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P67870
Assay: Inhibition Assay: Test compounds dissolved and diluted in DMSO (2 μl) were added to a reaction mixture comprising 10 μl of 5× Reaction Buffer (40 mM MOPS pH 7.0, 5 mM EDTA), 10 μl of recombinant human PIM2 solution (4 ng PIM-2 dissolved in dilution buffer (20 mM MOPS pH 7.0; EDTA 1 mM; 5% Glycerol; 0.01% Brij 35; 0.1%; 0.1% 2-mercaptoethanol; 1 mg/ml BSA)) and 8 ul of water. Reactions were initiated by the addition of 10 ul of ATP Solution (49% (15 mM MgCl2; 75 uM ATP) 1% ([γ-33P]ATP: Stock 1 mCi/100 μl; 3000 Ci/mmol (Perkin Elmer)) and 10 ul of substrate peptide solution (RSRSSYPAGT (SEQ ID NO.: 6), dissolved in water at a concentration of 1 mM), Reactions were maintained for 10 min at 30° C. The reactions were quenched with 100 ul of 0.75% Phosphoric acid, then transferred to and filtered through a Phosphocellulose filter plate (Millipore, MSPH-N6B-50). After washing each well 4 times with 0.75% Phosphoric acid, scintillation fluid (20 uL) was added to each well and the resid
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 407.39, ALogP 1.68, HBA 9, HBD 3, PSA 131.77, QED 0.42
Compound (SMILES): CCN1CC(C)(C)Oc2nc(N3C4CCC3COC4)nc(-c3ccc(NC(=O)OCCO)cc3F)c2C1=O
InChIKey: YRNFMYQUBSEIPE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The test detects the phosphorylation of the substrate GFP-4EBP1 using a terbium-labelled antibody that is specific for the phospho-Thr46 epitope. Binding of the Tb-antibody to the phosphorylated GFP peptide allows the transfer of energy from Tb, excited at 340 nm, to GFP with an increase in the fluorescence emission of the GFP at 520 nm. The test is performed in 96-well format (Corning/Costar 96 black flat-bottomed half-wells plate, ref. 3694) in a total volume of 30 ul. To 1 ul of inhibitor in 100% DMSO are added (final concentrations) 400 nM of GFP-4EBP1 (Invitrogen PV4759), 8 uM of ATP, 200 ng/ml of enzyme (human recombinant aa mTOR 1360-2549, Invitrogen PV4753) in a buffer of HEPES 50 mM pH 7.5, EGTA 1 mM, MnCl2 10 mM, BSA 0.1 mg/ml, glycerol 0.5%, NV-10 0.1 mg/ml, DTT 2 mM. The mixture is incubated for 30 minutes at room temperature. 10 ul of solution are taken up and the reaction is quenched by adding 10 ul of Tb-antibody solution (Invitrogen PV4757)/EDTA.
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 529.57, ALogP 2.82, HBA 9, HBD 2, PSA 126.35, QED 0.58
Compound (SMILES): CC(C)(C)c1ccc(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C6CCOCC6)CC5)c([N+](=O)[O-])c4)c(Oc4ccc5[nH]ccc5c4)c3)CC2)c(-c2ccc(Cl)cc2)c1
InChIKey: BJXNNZHPBIDJTA-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Mus musculus
UniProt: P10417
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki = 13.48 nM (pChEMBL 7.869999885559082)
Descriptors: MW 960.6, ALogP 9.98, HBA 11, HBD 3, PSA 162.38, QED 0.07
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc2[nH]ccc12
InChIKey: BXQUXUDGWFIKPO-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Mus musculus
UniProt: P10417
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki = 4.558 nM (pChEMBL 8.34000015258789)
Descriptors: MW 951.49, ALogP 8.15, HBA 11, HBD 3, PSA 153.38, QED 0.09
Compound (SMILES): COCCn1c2ccccc2c2ccnc(CN(CCCN3CCNCC3)[C@H]3CCCc4cccnc43)c21
InChIKey: HBVFWULQULOZOQ-LJAQVGFWSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Calcium Mobilization Assay: Functional modulation of CXCR4 was determined by calcium mobilization assay using leukemic lymphoid CEM cells, which naturally express high levels of CXCR4. Generally, the assay is carried out as follows: Cells are grown in vitro to confluency. On the day of the assay, cells are removed from the incubator, culture medium removed and replaced with a calcium sensitive dye (Calcium3 assay kit; Molecular Devices, Sunnyvale, Calif.). The cells are allowed to dye load for 45-60 min at 37 °C. in the cell culture incubator and then allowed to equilibrate to room temperature for no more than 15 min before assay. Compound plates were generated containing up to 3% dimethyl sulfoxide in media kept at room temperature. Test compounds were added to the cells at a 1:3 dilution, and calcium mobilization was measured using a Flex Station fluorescence imager (Molecular Devices). This first read was used to determine direct agonist activation of the CXCR4 receptor by the test compounds.
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 512.7, ALogP 4.41, HBA 7, HBD 1, PSA 58.45, QED 0.34
Compound (SMILES): CCC1CCCCN1C(=O)n1cc(-c2ccc(-c3ccccc3)cc2)nn1
InChIKey: MOAKLJWNGBAHTR-UHFFFAOYSA-N
Target: Diacylglycerol lipase-beta (SINGLE PROTEIN), Mus musculus
UniProt: Q91WC9
Assay: Inhibition of recombinant mouse DAGLbeta expressed in HEK293T cell membranes using PNP butyrate as substrate by colorimetric assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 360.46, ALogP 4.84, HBA 4, HBD 0, PSA 51.02, QED 0.67
Compound (SMILES): NC(=O)c1nn(-c2ccc(S(=O)(=O)CC3CC3)cc2)c2c1CCc1ccc(NC(=O)c3ccccc3Cl)cc1-2
InChIKey: BMBPFXUPSZIMBS-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of human recombinant C-terminal FLAG-epitope-tagged IKK2 expressed in baculovirus using biotinylated IkappaBalpha peptide as substrate assessed as decrease in [gamma-33P]-ATP incorporation in substrate after 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 561.06, ALogP 4.83, HBA 6, HBD 2, PSA 124.15, QED 0.33
Compound (SMILES): CC(C)C(=O)NC(c1nnc(CNS(N)(=O)=O)o1)c1nc2ccc(-c3ccccc3)cc2s1
InChIKey: NQOPDMVRWMCFFD-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase activity was measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 285 uL, of 1 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 15 uL, of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen and resuspended in 150 uL, of 50 mM HEPES pH 8.0 buffer containing 100 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at rt for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.05 for the FRET substrate.The enzymatic assay was measured using white, opaque 96-well half area plates. Each well contained 60 uL, of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 2 ul of a DMSO solution containing compound of interest. Conditioned media obtained from HT-1080 cells.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 486.58, ALogP 2.5, HBA 8, HBD 3, PSA 153.1, QED 0.35
Compound (SMILES): CCn1nc(-c2cccc(-c3cccc(O)c3F)c2)cc(NC(=O)Nc2c(Cl)cncc2Cl)c1=O
InChIKey: GPQYBMBSGLBMCH-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human recombinant PDE4B1 assessed as reduction in [3H]cAMP hydrolysis to [3H]AMP incubated for 60 mins by PDE-SPA assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 514.34, ALogP 5.79, HBA 6, HBD 3, PSA 109.14, QED 0.31
Compound (SMILES): COc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4c(F)cccc4F)c3F)c12
InChIKey: GVTHJUGFVUSNNB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf (unknown origin) assessed as decrease in biotin-tagged MEK1 phosphorylation after 45 mins
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 479.41, ALogP 4.16, HBA 5, HBD 2, PSA 101.15, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCNS(C)(=O)=O)c4)nc3c2)c1
InChIKey: JLVYDBJMHNJJKE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 645.65 nM (pChEMBL 6.190000057220459)
Descriptors: MW 522.63, ALogP 3.61, HBA 9, HBD 1, PSA 111.47, QED 0.32
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)c1ccc(F)c(-c2cccnc2)c1
InChIKey: IQEVNBWPJXRHBG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Radiometric Filter-Binding Assay: For determination of ABL kinase activity, the radiometric filter-binding assay was used. The assay was performed by mixing 10 μL of the compound pre-diluted with 10 μL of ATP (20 M 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 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 376.31, ALogP 5.04, HBA 3, HBD 1, PSA 51.22, QED 0.65
Compound (SMILES): Cc1ccc(C2=C(c3nnn[nH]3)C(=O)NC(c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)C2)cc1
InChIKey: AEMPUAWUDAMJBV-UHFFFAOYSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: Inhibition of human MGAT2 using 2-oleoylglycerol and oleoyl-coenzyme A as substrate by LC-MS analysis
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 525.45, ALogP 5.12, HBA 5, HBD 2, PSA 92.79, QED 0.33
Compound (SMILES): CS(=O)(=O)c1ccc(Nc2ncnc(OC3C[C@H]4CC[C@H](C3)N4C(=O)OCC3CC3)c2[N+](=O)[O-])c(F)c1
InChIKey: XCVJFKBEJKZIRB-HUUCEWRRSA-N
Target: Glucose-dependent insulinotropic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDV5
Assay: Agonist activity at human GPR119 expressed in HEK293 cells assessed as stimulation of cAMP level measured after 60 mins by HTRF assay
Measurement: EC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 535.55, ALogP 3.59, HBA 10, HBD 1, PSA 153.86, QED 0.39
Compound (SMILES): O=C1CCc2cc(CO)c(OCCCN3CCN(c4cccc5sccc45)CC3)cc2N1
InChIKey: KVJMESRMJOEXDV-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Dopamine D2 Receptor Binding Assay: The assay was performed according to the method by Kohler et al. (Kohler C, Hall H, Ogren S O and Gawell L, Specific in vitro and in vivo binding of 3H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. Biochem. Pharmacol., 1985; 34: 2251-2259). The binding assay was performed using 40 ul of the membrane specimen, 20 ul of [3H]-raclopride (final concentration 1 to 2 nM), 20 ul of a test drug and 50 mM Tris-hydrochloric acid buffer (containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, pH 7.4) so that the total amount was 200 ul (final dimethylsulfoxide concentration 1%). The reaction was performed at room temperature for 1 hour and terminated by conducting suction filtration with a cell harvester on a glass fiber filter plate. The filter plate made of glass fiber was washed with 50 mM Tris-hydrochloric acid buffer (pH 7.4), and after dried, a microplate liquid scintillation cocktail was added.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 451.59, ALogP 3.87, HBA 6, HBD 2, PSA 65.04, QED 0.53
Compound (SMILES): CCCNC(=O)c1ccc(NC(=O)N2Cc3ccc(OC)cc3C2)cc1
InChIKey: AEMMVMFCIBYFIX-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay : Probe 2:The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb-anti-His antibody (Invitrogen, Cat #PV5895), and 200 nM probe (Oregon Green 488-conjugated APO0866; A-1287128.0. Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 353.42, ALogP 3.38, HBA 3, HBD 2, PSA 70.67, QED 0.87
Compound (SMILES): Cc1c([C@@H](O)CN2CCCC3(CCCN(C(=O)c4ccc(-n5cnnn5)nc4)C3)C2)ccc2c1COC2=O
InChIKey: MKXHJPBSXYFHLC-DCCUJTHKSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37° C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25° C.) for 90 min. The loading buffer is replaced with assay buffer test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate. Step Protocol 1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates 2. Allow cells to adhere overnight in humidified 37° C./10% CO2 incubator 3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer 4. Incubate Microplate at room temperature, protected form light, for 90 min 5. Remove loading buffer and replace with 25 ul 1x Assay BufferÂ±test compound.Â  6. Incubate microplate at room temperature, protected form light, for 30 min 7. At FLIPR-Tetra 384: Add stimulant (Thallium/Potassium) solution to microplate and monitor fluorescence. Excitation=400 nm, Emission=460 & 580 nm. Collect data for 10 min.Â  Data Calculation: The fluorescence intensity of wells containing 3 uM of a standard control ROMK inhibitor of the present invention is used to define the ROMK-sensitive component of thallium flux. Fluorescence in the presence of test compounds is normalized to control values to provide % fluorescence change. IC50 values represent the concentration of compound that inhibits 50% of the ROMK thallium flux signal.
Measurement: IC50 = 86.33 nM (pChEMBL 7.059999942779541)
Descriptors: MW 517.59, ALogP 2.09, HBA 10, HBD 1, PSA 126.57, QED 0.51
Compound (SMILES): Cc1cc(Nc2cc(C(F)(F)F)ccn2)nc(-c2ccc(NC3CCN(C(=O)Cc4cccc(Cl)c4)CC3)nc2)c1
InChIKey: SWUHXNWPJDYNRE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Homogeneous Time-Resolved Fluorescence (HTRF) Assay: A recombinant GST-hSyk fusion protein was used to measure potency of compounds to inhibit human Syk activity. The recombinant human GST-Syk (Carna Biosciences #08-176) (5 pM final concentration) was incubated with various concentrations of the inhibitor diluted in DMSO (0.1% final concentration) for 10 minutes at room temperature in 15 mM Tris-HCl (pH 7.5), 0.01% tween 20, 2 mM DTT in 384 well plate format. To initiate the reaction the biotinylated substrate peptide (250 nM final concentration) that contains the phosphorylation site for Syk was added with magnesium (5 mM final concentration) and ATP (25 uM final concentration). Final volume of the reaction was 10 uL. Phosphorylation of the peptide was allowed to proceed for 45x at room temperature. To quench the reaction and detect the phosphorylated product, 2 nM of a Europium-anti-phosphotyrosine antibody (Perkin Elmer #AD0161) and 70 nM SA-APC (Perkin-Elmer #CR130-100) were added together in 15 mM Tris pH 7.5.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 581.04, ALogP 6.91, HBA 6, HBD 2, PSA 83.04, QED 0.25
Compound (SMILES): CCCC(C(=O)O)c1c(C)nc2ccc3c(c2c1-c1ccc(C)cc1)CCCC3
InChIKey: CNBVIGBVPQPTAE-UHFFFAOYSA-N
Target: PC4 and SFRS1-interacting protein (SINGLE PROTEIN), Homo sapiens
UniProt: O75475
Assay: Alpha Screen Interaction Assay: An AlphaScreen assay was performed according to the manufacturer's protocol (Perkin Elmer, Benelux). Reactions were performed in 25 ul final volume in 384-well Optiwell microtiter plates (Perkin Elmer). The reaction buffer contained 25 mM Tris-HCl (pH 7.4), 150 mM NaCl, 1 mM MgCl2, 0.01% (v/v) Tween-20 and 0.1% (w/v) bovine serum albumin. His6-tagged integrase (300 nM final concentration) was incubated with the compounds for 30 min at 4 C. The compounds were added at varying concentrations spanning a wide range from 0.1 up to 100 uM. Afterwards 100 nM flag-LEDGF/p75 was added and incubation was prolonged for an additional hour at 4 C. Subsequently 5 ul of Ni-chelate-coated acceptor beads and 5 ul anti-flag donor beads were added to a final concentration of 20 ug/ml of both beads. Proteins and beads were incubated for 1 h at 30 C. in order to allow association to occur. Exposure of the reaction to direct light was omitted as much as possible.
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 387.52, ALogP 6.37, HBA 2, HBD 1, PSA 50.19, QED 0.55
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4ccc5nc(N)cn5c4)c4c(N)ncnc43)n(-c3ccccc3)c(=O)c12
InChIKey: WVMQKDOKTBOMEO-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 513.57, ALogP 3.97, HBA 10, HBD 2, PSA 134.94, QED 0.36
Compound (SMILES): Cc1c(-c2ccc(C(F)(F)F)cc2)nnc(N2CCN(c3cnc(C(=O)O)cn3)[C@H](C)C2)c1C
InChIKey: RUOYEUMJKZIONP-CYBMUJFWSA-N
Target: Protein smoothened (SINGLE PROTEIN), Mus musculus
UniProt: P56726
Assay: Inhibition of mouse recombinant Shh protein in mouse TMHh12 cells assessed as inhibition of 1 nM Smo agonist-induced hedgehog signalling response by Gli-luciferase reporter gene assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 472.47, ALogP 3.98, HBA 7, HBD 1, PSA 95.34, QED 0.61
Compound (SMILES): COc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1OCC1CN(C)CCO1
InChIKey: ZPNITDGPLQDXIJ-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: Inhibition of recombinant human N-terminal His6-tagged EphB4 kinase domain (E605 to E890 residues) expressed in baculovirus using poly-AEKY as substrate after 150 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 477.33, ALogP 3.99, HBA 7, HBD 1, PSA 68.74, QED 0.58
Compound (SMILES): O=C(NCCCCc1ccc(F)cc1)N1Cc2ccc(CO)cc2C1
InChIKey: YGPPFQAFROZGSQ-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay : Probe 2:The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb-anti-His antibody (Invitrogen, Cat #PV5895), and 200 nM probe (Oregon Green 488-conjugated APO0866; A-1287128.0. Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
Measurement: IC50 = 60.2 nM (pChEMBL 7.21999979019165)
Descriptors: MW 342.41, ALogP 3.37, HBA 2, HBD 2, PSA 52.57, QED 0.79
Compound (SMILES): Cc1ncc(-c2ccn(C)c(=O)c2)c(OC[C@@H]2C[C@H]2c2ccc(F)cn2)n1
InChIKey: OLCBJQIRZNGQJB-GOEBONIOSA-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 = 88.4 nM (pChEMBL 7.050000190734863)
Descriptors: MW 366.4, ALogP 2.87, HBA 6, HBD 0, PSA 69.9, QED 0.69
Compound (SMILES): CN(C)Cc1ccc(CSCCN2C(=O)c3ccccc3C2=O)o1
InChIKey: VCCTWUFHIQYYHA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine as substrate preincubated for 8 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 3570 nM (pChEMBL 5.449999809265137)
Descriptors: MW 344.44, ALogP 2.87, HBA 5, HBD 0, PSA 53.76, QED 0.57
Compound (SMILES): O=C(N[C@H]1CC[C@H](c2ccc(NC(=O)N3Cc4ccncc4C3)cc2)CC1)[C@@H]1CCCO1
InChIKey: DFGBXHILEMKPIA-HYVJGQCMSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay : Probe 2:The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb-anti-His antibody (Invitrogen, Cat #PV5895), and 200 nM probe (Oregon Green 488-conjugated APO0866; A-1287128.0. Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
Measurement: IC50 = 8.81 nM (pChEMBL 8.050000190734863)
Descriptors: MW 434.54, ALogP 3.95, HBA 4, HBD 2, PSA 83.56, QED 0.76
Compound (SMILES): Cc1cc(-c2cccc(F)c2)cc(CNc2c(F)ccc(OCC(=O)O)c2C)c1C
InChIKey: MMANJBFLFZMHPK-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Cellular Functional Assay: Human CHO cells expressing the recombinant human prostanoid EP2 receptor were suspended in assay medium (HBSS buffer (Invitrogen) containing 20 mM HEPES (pH7.4) and 500 μM isobutyl-methylxanthine IBMX) and plated out to yield approximately 1×104 cells/well in a 96-well. Following this, cells were incubated with agonists for 30 min in the presence of the test compounds. For stimulated control measurements, separate assay wells contain 10 μM PGE2 (control specific agonist). All incubations were carried out at 37° C. in a 5% CO2 atmosphere. Following incubation, the amount of cAMP in each well was determined by HTRF method. The cells are lysed and the fluorescence acceptor (D2-labeled cAMP) and fluorescence donor (anti-cAMP antibody labeled with europium cryptate) are added.
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 411.45, ALogP 5.63, HBA 3, HBD 2, PSA 58.56, QED 0.53
Compound (SMILES): CC(C)OC(=O)/C=C\n1cnc(-c2cc(OC(C)C)cc(C(F)(F)F)c2)n1
InChIKey: DEDQCKRCFDIKKK-WAYWQWQTSA-N
Target: Exportin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14980
Assay: Inhibition of Crm1 in human U2OS cells expressing GFP-fused HIV1 Rev assessed as decrease in nuclear export of GFP-fused HIV1 Rev after 1 hr by Hoechst 33258 staining-based assay
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 383.37, ALogP 4.17, HBA 6, HBD 0, PSA 66.24, QED 0.55
Compound (SMILES): COC(=O)c1ccc(S(=O)(=O)N(Cc2ccc(F)c(C(F)(F)F)c2)c2sc3ccccc3c2C(C)C)cc1
InChIKey: YREOKAXVKYKNRD-UHFFFAOYSA-N
Target: Transient receptor potential M8 protein (SINGLE PROTEIN), Canis lupus familiaris
UniProt: Q1A7N1
Assay: Functional 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. Subsequently, cells were tested for agonist-induced increases in intracellular Ca2+ levels using FLIPR or FDSS. Cells were challenged with a compound of the Formula (I) (at varying concentrations) and intracellular Ca2+ was measured for 5 min prior to the addition of icilin to all wells to achieve a final concentration that produces approximately an 80% maximal response. EC50 or IC50 values for compounds of the present invention were determined from eight-point dose-response studies.
Measurement: IC50 = 49.3 nM (pChEMBL 7.309999942779541)
Descriptors: MW 565.61, ALogP 7.36, HBA 5, HBD 0, PSA 63.68, QED 0.17
Compound (SMILES): CC(C)(C)OC(=O)N1CC(c2ccc3c(c2)C(=O)N[C@H](C(=O)NC2(C#N)CC2)Cc2ccc(c(Cl)c2)OCCCCO3)C1
InChIKey: GNVTXPDSHMMZIX-VWLOTQADSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Cathepsin Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide. Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DDT 5 mM. Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat LSubstrate (20 uM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem). Z=Benzyloxycarbonyl. AMC=7-Amino-4-Methyl-Coumarin. Final volume: 100 uL. Excitation 360 nm, Emission 465 nm. Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 25.5 nM (pChEMBL 7.590000152587891)
Descriptors: MW 609.12, ALogP 4.74, HBA 7, HBD 2, PSA 129.99, QED 0.51
Compound (SMILES): Nc1n[nH]c2c1C(c1ccc(F)c(F)c1)c1c(N)n[nH]c1O2
InChIKey: UHOHXUKJFWJNNY-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of N-terminus 6xHis-tagged human IDO1 expressed in Escherichia coli M15 using L-tryptophan as substrate preincubated for 1 hr measured after 15 mins in presence of bovine liver and methylene blue by spectrophotometric analysis
Measurement: IC50 = 239 nM (pChEMBL 6.619999885559082)
Descriptors: MW 304.26, ALogP 1.86, HBA 5, HBD 4, PSA 118.63, QED 0.43
Compound (SMILES): CC(=O)Nc1cc(NC(=O)Nc2ccc(Oc3ccnc(NC(=O)C4CC4)c3)c(F)c2)cc(C(F)(F)F)c1
InChIKey: LGZIXEVNBUGLPI-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: [Experimental method]: Use Lance@Ultra Ulight™-TK assay kit from PerKinElmer to evaluate the inhibitory activity of compounds at KDR kinase. [Instrument]: PerKinElmer's ENVISION plate reader. [Materials]: Optiplate-384 well plate (PerKinElmer), kinase buffer (50 mM Hepes pH7.5, 0.25 mM EGTA, 2 mM DTT, 0.01% Tween 20, 10 mM Mg2+, 0.5 mM Mn2+), KDR kinase (790-1356 AA, Crown Bioscience), KDR kinase substrate (PerKinElmer catalogue # TRF0127-M), Lance@Eu-W1024-anti-phosphotyrosine (PT66) (PerKinElmer, catalogue #AD0068), ATP (Invitrogen), DMSO (Sigma, catalogue #34869), purified water (Millipore, type: Milli-Q). [Study conditions]: Mix KDR (final concentration: 20 nM) and compound (final DMSO: 0.5%), pre-incubate for 20 min at 30° C.; then add ATP (final concentration: 90 μM) and the substrate (final concentration 50 μM). React for 2 hrs at 30° C. After the reaction, add antibody and reaction for 60 min at 30° C. Read the plate (615 nm, 665 nm), calculate the ratio of the value at 665 nm vs 615 nm and analyze the data.
Measurement: IC50 = 14.2 nM (pChEMBL 7.849999904632568)
Descriptors: MW 531.47, ALogP 5.98, HBA 5, HBD 4, PSA 121.45, QED 0.28
Compound (SMILES): CC(C)(C)c1cc(NC(=O)c2ccc3cc4n(c3c2)CCCNC4=O)no1
InChIKey: MSPIIJQNGRPYLL-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Kinase Glo Plus Assay: Human RSK2 protein, purchased from Invitrogen, is used to measure kinase activity utilizing Kinase Glo Plus (Promega) a homogeneous assay technology, which uses a luciferin-luciferase based ATP detection reagent to quantify residual ATP. The assay is performed using 0.75 nM His-RSK2, 0.75 .mu.M ATP and 1.0 uM S6 Kinase/RSK Substrate Peptide 1 (Upstate, catalog #12-124), in assay buffer consisting of 25 mM HEPES, pH 7.5, 10 mM MgCl2, 5 mM MnCl2, 50 mM KCl, 0.2% BSA, 0.01% CHAPS, 100 uM Na3VO4, 0.5 mM DTT, and 1% DMSO. Solutions of test compounds at various concentrations are prepared by 1:3 fold serial dilution of a 1 mM solution of compound in DMSO. The DMSO solutions are further diluted with assay buffer to a final concentration of DMSO of 5%. The assay is performed in a 384 well, white, non-binding plate (Corning, catalogue #3574). Solutions of test compounds (10 uL) are transferred to a dry assay plate, followed by addition of 20 uL kinase.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 366.42, ALogP 3.31, HBA 5, HBD 2, PSA 89.16, QED 0.73
Compound (SMILES): Cc1cccc(F)c1S(=O)(=O)NC1(C(=O)NC2C3CC4CC2CC(C(N)=O)(C4)C3)CC1
InChIKey: YPCUCXCZFDUIFP-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: HTRF Assay : The inhibiting activity of 11β-HSD1 derived from microsomal fractions was measured using the HTRF assay (62CO2PEB, Cisbio). Different concentrations of compounds were added to 96-well plates, followed by the addition of TE buffer (20 mM Tris buffer and 5 mM EDTA, pH 6.0) containing 200 μM NADPH (N1630, Sigma) and 160 nM cortisone (C2755, Sigma), The reactions were initiated by the addition of human microsomal fractions (M0317, Sigma), and were allowed to incubate for 2 h at 37° C. Europium (Eu3+) cryptate and XL665-conjugated cortisol were then added to each well and incubated for an additional 2 h at room temperature.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 449.55, ALogP 1.74, HBA 4, HBD 3, PSA 118.36, QED 0.61
Compound (SMILES): C[C@@H](O)[C@H](CO)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](N)Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@H](Cc2c(C(F)(F)F)[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1
InChIKey: HYPZBXNFDIOACN-WNIOSIORSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Binding affinity to human SST2 receptor
Measurement: Kd = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 1087.26
Compound (SMILES): CCNc1nc(Nc2cnn3c2C(C)OCC3)ncc1C(F)(F)F
InChIKey: OKNQEWAOCLIHFE-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Lanthascreen Binding Assay: This assay was used to determine a compound's potency in inhibiting activity of LRRK2 by determining, Kiapp, IC50, or percent inhibition values. In 384 well proxiplates F black, shallow well plates LRRK2, Eu-anti-GST-antibody, Alexa Fluor Kinase tracer 236 and test compound were incubated together.Binding of the Alexa Fluor tracer to a kinase is detected by addition of a Eu-labeled anti-GST antibody. Binding of the tracer and antibody to a kinase results in a high degree of FRET, whereas displacement of the tracer with a kinase inhibitor results in a loss of FRET. Assay conditions and materials used were as follows: Final Assay Conditions:    GST-LRRK2 G2019S 10 nM Eu-anti-GST-antibody 2 nM    Kinase tracer 236 8.5 nM    Kinase reaction time: 1 hour    Temperature: ambient    Total volume: 15 ul    DMSO 1% Materials: 384 well proxiplates F black shallow well Perkin Elmer cat #6008260Kinase: LRRK2 G2019S, Invitrogen cat # PV4882 (LOT 567054A).
Measurement: Ki = 47.7 nM (pChEMBL 7.320000171661377)
Descriptors: MW 342.32, ALogP 2.96, HBA 7, HBD 2, PSA 76.89, QED 0.89
Compound (SMILES): COc1cc(C(F)(F)F)ccc1N1C(=O)[C@H](C)Oc2cc(S(=O)(=O)Nc3nccs3)ccc21
InChIKey: IQGDMZMIADQDQK-NSHDSACASA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: In Vitro PX Assay: HEK 293 cells stably transfected with human Nav1.7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, Calif.). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to −10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes.
Measurement: IC50 = 596 nM (pChEMBL 6.21999979019165)
Descriptors: MW 499.49, ALogP 4.42, HBA 7, HBD 1, PSA 97.83, QED 0.56
Compound (SMILES): COc1ccc([C@@H]2O[C@H](c3ccc(OC(C)C(O)c4ccc5c(c4)OCO5)c(OC)c3)[C@H](C)[C@@H]2C)cc1OC
InChIKey: HVQJVSACIKTWQR-HZFJSAMJSA-N
Target: Sterol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35610
Assay: Inhibition of human ACAT1
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 536.62, ALogP 6.03, HBA 8, HBD 1, PSA 84.84, QED 0.36
Compound (SMILES): CC(C)(C)c1ccc(-c2c(-c3cccc(OC(F)(F)F)c3)cc3n2[C@@H](CCN)CNC3=O)cc1
InChIKey: AWLKBZZAGUKGIX-IBGZPJMESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Trans-Phosphorylation Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds were determined using a trans-phosphorylation assay.Specific peptide or protein substrates were trans-phosphorylated by their specific ser-thr or tyr kinase in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors. At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP were captured by an excess of the ion exchange dowex resin; the resin then settled down to the bottom of the reaction plate by gravity. Supernatant was subsequently withdrawn and transferred into a counting plate, then evaluated by beta-counting. Kinase Buffer (KB):The buffer for PIM2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 uM Na3VO4, and 0.2 mg/mL BSA.Â  Full-length human PIM2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 471.52, ALogP 5.65, HBA 4, HBD 2, PSA 69.28, QED 0.51
Compound (SMILES): O=C(c1cc(-c2cc(Cl)ccc2C(=O)N2Cc3ccccc3C[C@H]2CN2CCOCC2)n2c1CCCC2)N(c1ccc(O)cc1)c1ccc(F)c(F)c1
InChIKey: YLTHERAEXXNQEQ-YTTGMZPUSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Mus musculus
UniProt: P10417
Assay: Fluorescence Polarisation Assay: The fluorescence polarisation tests were carried out on microplates (384 wells). The Bcl-2 protein, at a final concentration of 2.50×10−8 M, is mixed with a fluorescent peptide (Fluorescein-REIGAQLRRMADDLNAQY), at a final concentration of 1.00×10−8 M in a buffer solution (Hepes 10 mM, NaCl 150 mM, Tween20 0.05%, pH 7.4), in the presence or in the absence of increasing concentrations of test compounds. After incubation for 2 hours, the fluorescence polarisation is measured.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 737.25, ALogP 8.01, HBA 6, HBD 1, PSA 78.25, QED 0.18
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4C)nc3c2)c1
InChIKey: SQPOQDJDYNYPIZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 123.03 nM (pChEMBL 6.909999847412109)
Descriptors: MW 460.58, ALogP 4.49, HBA 8, HBD 1, PSA 77.33, QED 0.39