lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCCC[C@H]2C(=O)N1
InChIKey: ZDTMGSSRQLKYTK-UGSOOPFHSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 520.39, ALogP 4.56, HBA 7, HBD 2, PSA 88.61, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CCN2C[C@@H]3C[C@H]2CN3)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: NQVUICANYJFDGS-CQERKEQDSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 485.59, ALogP 3.23, HBA 9, HBD 1, PSA 80.57, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VQXBFPOCHKNAOT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 26.3 nM (pChEMBL 7.579999923706055)
Descriptors: MW 492, ALogP 6.1, HBA 8, HBD 0, PSA 65.3, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2cccc(Br)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JBJLDYOTZAKYCV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 8.318 nM (pChEMBL 8.079999923706055)
Descriptors: MW 531.41, ALogP 5.54, HBA 8, HBD 0, PSA 78.19, QED 0.26
Compound (SMILES): Cc1ccc(NC(=O)CCCCCC(=O)Nc2ccccc2N)cc1
InChIKey: WTKBRPXPNAKVEQ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: HDAC enzyme inhibitionAssay: HDAC enzyme inhibition assays were performed using purified HDACs 1-10 essentially as described in Beckers et al., 2007, Int. J. Cancer., 121:1138-48 and Perez-Balado et al., 2007, J. Med. Chem., 50:2497-2505. Inhibition assays using nuclear extract were performed essentially as described in Herman et al., 2006, Nat. Chem. Biol., 2:551-558. Briefly, the purified HDACs or nuclear extract were incubated with an acetylated substrate in the absence of the compound to be assayed and with increasing concentrations of the compound. The rate of substrate deacetylation was measured under each condition, and half-maximal inhibitory concentration with regard to each HDAC was determined by standard means.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 339.44, ALogP 4.1, HBA 3, HBD 3, PSA 84.22, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(C/C(=N/O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HRMKTZOBLPIBBW-GNVQSUKOSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 46.77 nM (pChEMBL 7.329999923706055)
Descriptors: MW 460.54, ALogP 4.67, HBA 9, HBD 1, PSA 97.89, QED 0.23
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(O)cc(Br)c12
InChIKey: JKAWTKSLLNVOJM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 379.25, ALogP 3.28, HBA 4, HBD 2, PSA 65.56, QED 0.8
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CCNC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JJPFEPQJBUBRFW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 484.56, ALogP 2.91, HBA 9, HBD 2, PSA 97.56, QED 0.4
Compound (SMILES): Cc1nc2c(C(N)=O)cc(N3CCOCC3)nn2c1Cc1cccc(C(F)(F)F)c1C
InChIKey: LIQQLHSREQDUHL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 433.43, ALogP 2.89, HBA 6, HBD 1, PSA 85.75, QED 0.68
Compound (SMILES): COc1cccc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NTDPWPKQOCPZDC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 407.38 nM (pChEMBL 6.389999866485596)
Descriptors: MW 505.58, ALogP 5.25, HBA 8, HBD 0, PSA 74.53, QED 0.28
Compound (SMILES): Cc1nc(C(N)=O)ccc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: WEEBXSDEOQNZPK-NLFFAJNJSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in microsomes using ER as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.62, ALogP 4.67, HBA 7, HBD 1, PSA 89.93, QED 0.34
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(OCCCN5CCCC5)nc4)cc23)c1F
InChIKey: UJQYWQCKAHYIAY-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 583.66, ALogP 5.15, HBA 7, HBD 2, PSA 117.28, QED 0.17
Compound (SMILES): COc1cc(OC)cc(N(C[C@H](O)CNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: PUCMKYWRDKWWQJ-ZMBIFBSDSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.455 nM (pChEMBL 8.609999656677246)
Descriptors: MW 476.58, ALogP 3.54, HBA 9, HBD 2, PSA 97.56, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: VFFSRBOFGPSKTB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.818 nM (pChEMBL 8.550000190734863)
Descriptors: MW 432.53, ALogP 4.19, HBA 8, HBD 1, PSA 91.32, QED 0.45
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4ccccc4F)c3F)c2c1
InChIKey: GJXLXHVXNBAYQU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.4, ALogP 3.88, HBA 5, HBD 2, PSA 115.71, QED 0.44
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccccc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GHWXUQIYJKZOLT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 21.38 nM (pChEMBL 7.670000076293945)
Descriptors: MW 451.53, ALogP 5.39, HBA 7, HBD 0, PSA 65.3, QED 0.33
Compound (SMILES): Cl.Clc1ccc2sc(CCCCN3CCC4CCCCC4C3)nc2c1
InChIKey: LLHIQLAPTLWBMG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-mesulergine from human 5-HT2C receptor by liquid scintillation counting method
Measurement: Ki = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 362.97, ALogP 5.78, HBA 3, HBD 0, PSA 16.13, QED 0.63
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(-c2ncco2)cc1
InChIKey: NIFGQHGFOUMQJN-KCWPFWIISA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in microsomes using MMC as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 539.63, ALogP 6.52, HBA 7, HBD 0, PSA 59.98, QED 0.19
Compound (SMILES): COc1cn(C(CC2CCCOC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: SNVIVXDTJLCEGY-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 535.98, ALogP 4.74, HBA 7, HBD 2, PSA 130.65, QED 0.43
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)c(OC(F)(F)F)c2)cc(OC)c1
InChIKey: RNUOMGDKVIMQSL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 446.45, ALogP 4.03, HBA 6, HBD 2, PSA 85.89, QED 0.6
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc4c(=O)n(Cc5ccc(F)cc5)nnc4cc3F)cc12
InChIKey: MKUFAWDAPBDDKS-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase S365A mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 46.7 nM (pChEMBL 7.329999923706055)
Descriptors: MW 647.64, ALogP 5.09, HBA 8, HBD 1, PSA 127.4, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(CCn2cnnc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RUROKZDZIPBDNX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 456.51, ALogP 3.48, HBA 10, HBD 0, PSA 96.01, QED 0.35
Compound (SMILES): C[C@@H]1C[C@H](N)CN(c2ccncc2Nc2ncc3ccc(-c4c(F)cccc4F)nn23)C1
InChIKey: BYFQNMWZRKKFRI-CABCVRRESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: PIM Enzyme Assay: The assay for the determination of Pim activity is based on the formation of phosphorylated biotinylated-BAD peptide at the Serine 112 residue (S112) and employs HTRF (homogeneous time resolved fluorescence) technology to detect the product in a 96-well plate format. The phosphorylation of biotinylated-BAD (S112) peptide by full length recombinant Pim-1, Pim-2, or Pim-3 protein was detected with streptavidin:Allophycocyanin (APC) conjugate and a europium (Eu) labeled antibody directed against phosphorylated-BAD (S112). Excitation of Eu by a high energy laser light (337 nm) leads to a transfer of energy to the APC molecule, and results in an emission at 665 nm. The fluorescence is directly proportional to the amount of phosphorylated BAD peptide present in the reaction.Compounds were prepared in DMSO by conducting 3-fold serial dilutions to give a 10-point dosing curve having a high dose of 1 uM. A reference compound was included on each assay plate in order to validate that plate.
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 435.48, ALogP 3.99, HBA 7, HBD 2, PSA 84.37, QED 0.5
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCN)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NHSCTFBEZPHZRZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.514 nM (pChEMBL 8.819999694824219)
Descriptors: MW 475.55, ALogP 2.74, HBA 9, HBD 2, PSA 120.42, QED 0.36
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnc(N(C)C)nc4)cc23)c1F
InChIKey: CNMJRJRTAYPAML-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 500.53, ALogP 3.75, HBA 7, HBD 2, PSA 120.94, QED 0.35
Compound (SMILES): O=C(CCc1ccc(Cl)cc1CN1CCC[C@H]1c1nc(C(=O)NCCCCC2CCCCC2)co1)NS(=O)(=O)C(F)(F)F
InChIKey: XTSILTSKUZERSP-VWLOTQADSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Cell Based Assay: Ca2+ signaling studies were performed using a FLIPR TETRA system (Molecular Devices, Sunnyvale, Calif., USA) in the 384-format. This is a high-throughput instrument for cell-based assays to monitor Ca2+ signaling associated with GPCRs and ion channels. Cells were seeded at a density of 5×104 cells/well in BioCoat poly-D-lysine coated, black wall, clear bottom 384-well plates (BD Biosciences, Franklin lakes, NJ, USA) and allowed to attach overnight in an incubator at 37° C. The cells were then washed twice with HBSS-HEPES buffer (Hanks' balanced salt solution without bicarbonate and phenol red, 20 mM HEPES, pH 7.4) using an ELx405 Select CW Microplate Washer (BioTek, Winooski, Vt., USA). After 60 min of dye-loading in the dark using the Ca2+-sensitive dye Fluo-4AM (Invitrogen, Carlsbad, Calif., USA), at a final concentration of 2×10^−6M, the plates were washed 4 times with HBSS-HEPES buffer to remove excess dye and leaving 50 μl of buffer in each well. The plates were then placed in the FLIPR TETRA instrument and allowed to equilibrate at 37° C. AGN-211377 was added in a 25 μl volume to each well to give final concentrations of 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, and 30 μM; or 0.067 μM, 0.1 μM, 0.2 μM, 0.3 μM, 0.67 μM, and 1 μM for cells over-expressing TP receptors. After 4.5 minutes, a 7-point serial dilution of the standard agonist for the corresponding receptor, in a 25 μl volume was injected at the final concentrations from 10^−11M to 10^−5M in 10-fold serial dilution increments for cells expressing human recombinant DP1, EP1, EP2, EP3, EP4, FP, and IP receptors. The dose range for the standard agonist for human recombinant TP receptors was from 10^−12M to 10^−6M. HBSS-HEPES buffer was used as the negative control for the standard agonists. Cells were excited with LED (light emitting diode) excitation at 470-495 nm and emission was measured through an emission filter at 515-575 nm. Assay plates were read for 3.5 minutes using the FLIPRTETRA.
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 647.16, ALogP 6.04, HBA 7, HBD 2, PSA 121.61, QED 0.25
Compound (SMILES): COC[C@@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-BOXHHOBZSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(F)(F)(F)(F)F)cc3)c(N)c2c1C
InChIKey: PSCQDXGBEMJRFR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-N-Methylscopolamine from human M1 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 438.45, ALogP 5.48, HBA 5, HBD 2, PSA 80.9, QED 0.53
Compound (SMILES): O=C(C1CCS(=O)(=O)C1)N1CC[C@](c2ccc(C(F)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: QABINSUJKJJFAK-FXMQYSIJSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human Gal4-fused RORbeta LBD (200 to 559 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 619.55, ALogP 4.45, HBA 5, HBD 0, PSA 88.59, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CCCO2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GBXSGEIAMQTWMD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.413 nM (pChEMBL 8.130000114440918)
Descriptors: MW 445.52, ALogP 4.36, HBA 8, HBD 0, PSA 74.53, QED 0.42
Compound (SMILES): COc1ncc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(NS(=O)(=O)c5c(F)cccc5F)c4F)c3c2)cn1
InChIKey: PJUYURNAWZJXJZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 557.49, ALogP 4.62, HBA 7, HBD 2, PSA 126.93, QED 0.22
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCCC[C@H]2C(=O)N1
InChIKey: ZDTMGSSRQLKYTK-UGSOOPFHSA-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 7.301000118255615)
Descriptors: MW 520.39, ALogP 4.56, HBA 7, HBD 2, PSA 88.61, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CCN2C[C@@H]3C[C@H]2CN3)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: NQVUICANYJFDGS-CQERKEQDSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.623 nM (pChEMBL 8.25)
Descriptors: MW 485.59, ALogP 3.23, HBA 9, HBD 1, PSA 80.57, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VQXBFPOCHKNAOT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 492, ALogP 6.1, HBA 8, HBD 0, PSA 65.3, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2cccc(Br)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JBJLDYOTZAKYCV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 8.913 nM (pChEMBL 8.050000190734863)
Descriptors: MW 531.41, ALogP 5.54, HBA 8, HBD 0, PSA 78.19, QED 0.26
Compound (SMILES): Cc1ccc(NC(=O)CCCCCC(=O)Nc2ccccc2N)cc1
InChIKey: WTKBRPXPNAKVEQ-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: HDAC enzyme inhibitionAssay: HDAC enzyme inhibition assays were performed using purified HDACs 1-10 essentially as described in Beckers et al., 2007, Int. J. Cancer., 121:1138-48 and Perez-Balado et al., 2007, J. Med. Chem., 50:2497-2505. Inhibition assays using nuclear extract were performed essentially as described in Herman et al., 2006, Nat. Chem. Biol., 2:551-558. Briefly, the purified HDACs or nuclear extract were incubated with an acetylated substrate in the absence of the compound to be assayed and with increasing concentrations of the compound. The rate of substrate deacetylation was measured under each condition, and half-maximal inhibitory concentration with regard to each HDAC was determined by standard means.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 339.44, ALogP 4.1, HBA 3, HBD 3, PSA 84.22, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(C/C(=N/O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HRMKTZOBLPIBBW-GNVQSUKOSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 460.54, ALogP 4.67, HBA 9, HBD 1, PSA 97.89, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CCNC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JJPFEPQJBUBRFW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 17.78 nM (pChEMBL 7.75)
Descriptors: MW 484.56, ALogP 2.91, HBA 9, HBD 2, PSA 97.56, QED 0.4
Compound (SMILES): COc1cccc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NTDPWPKQOCPZDC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 169.82 nM (pChEMBL 6.769999980926514)
Descriptors: MW 505.58, ALogP 5.25, HBA 8, HBD 0, PSA 74.53, QED 0.28
Compound (SMILES): Cc1nc(C(N)=O)ccc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: WEEBXSDEOQNZPK-NLFFAJNJSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 expressed in microsomes using FCA as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.62, ALogP 4.67, HBA 7, HBD 1, PSA 89.93, QED 0.34
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(OCCCN5CCCC5)nc4)cc23)c1F
InChIKey: UJQYWQCKAHYIAY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 583.66, ALogP 5.15, HBA 7, HBD 2, PSA 117.28, QED 0.17
Compound (SMILES): COc1cc(OC)cc(N(C[C@H](O)CNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: PUCMKYWRDKWWQJ-ZMBIFBSDSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.074 nM (pChEMBL 8.390000343322754)
Descriptors: MW 476.58, ALogP 3.54, HBA 9, HBD 2, PSA 97.56, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: VFFSRBOFGPSKTB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 432.53, ALogP 4.19, HBA 8, HBD 1, PSA 91.32, QED 0.45
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4ccccc4F)c3F)c2c1
InChIKey: GJXLXHVXNBAYQU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.4, ALogP 3.88, HBA 5, HBD 2, PSA 115.71, QED 0.44
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccccc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GHWXUQIYJKZOLT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.88 nM (pChEMBL 7.889999866485596)
Descriptors: MW 451.53, ALogP 5.39, HBA 7, HBD 0, PSA 65.3, QED 0.33
Compound (SMILES): Cl.Clc1ccc2sc(CCCCN3CCC4CCCCC4C3)nc2c1
InChIKey: LLHIQLAPTLWBMG-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H]-pyrilamine from human histamine H1 receptor by liquid scintillation counting method
Measurement: Ki = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 362.97, ALogP 5.78, HBA 3, HBD 0, PSA 16.13, QED 0.63
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(-c2ncco2)cc1
InChIKey: NIFGQHGFOUMQJN-KCWPFWIISA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in microsomes using DEF as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 539.63, ALogP 6.52, HBA 7, HBD 0, PSA 59.98, QED 0.19
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)c(OC(F)(F)F)c2)cc(OC)c1
InChIKey: RNUOMGDKVIMQSL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: Ki = 438 nM (pChEMBL 6.360000133514404)
Descriptors: MW 446.45, ALogP 4.03, HBA 6, HBD 2, PSA 85.89, QED 0.6
Compound (SMILES): COc1cc(OC)cc(N(CCn2cnnc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RUROKZDZIPBDNX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 17.78 nM (pChEMBL 7.75)
Descriptors: MW 456.51, ALogP 3.48, HBA 10, HBD 0, PSA 96.01, QED 0.35
Compound (SMILES): C[C@@H]1C[C@H](N)CN(c2ccncc2Nc2ncc3ccc(-c4c(F)cccc4F)nn23)C1
InChIKey: BYFQNMWZRKKFRI-CABCVRRESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: PIM Enzyme Assay: The assay for the determination of Pim activity is based on the formation of phosphorylated biotinylated-BAD peptide at the Serine 112 residue (S112) and employs HTRF (homogeneous time resolved fluorescence) technology to detect the product in a 96-well plate format. The phosphorylation of biotinylated-BAD (S112) peptide by full length recombinant Pim-1, Pim-2, or Pim-3 protein was detected with streptavidin:Allophycocyanin (APC) conjugate and a europium (Eu) labeled antibody directed against phosphorylated-BAD (S112). Excitation of Eu by a high energy laser light (337 nm) leads to a transfer of energy to the APC molecule, and results in an emission at 665 nm. The fluorescence is directly proportional to the amount of phosphorylated BAD peptide present in the reaction.Compounds were prepared in DMSO by conducting 3-fold serial dilutions to give a 10-point dosing curve having a high dose of 1 uM. A reference compound was included on each assay plate in order to validate that plate.
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 435.48, ALogP 3.99, HBA 7, HBD 2, PSA 84.37, QED 0.5
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCN)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NHSCTFBEZPHZRZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.479 nM (pChEMBL 8.829999923706055)
Descriptors: MW 475.55, ALogP 2.74, HBA 9, HBD 2, PSA 120.42, QED 0.36
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnc(N(C)C)nc4)cc23)c1F
InChIKey: CNMJRJRTAYPAML-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 500.53, ALogP 3.75, HBA 7, HBD 2, PSA 120.94, QED 0.35
Compound (SMILES): COC[C@@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-BOXHHOBZSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.802 nM (pChEMBL 8.420000076293945)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(F)(F)(F)(F)F)cc3)c(N)c2c1C
InChIKey: PSCQDXGBEMJRFR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-N-Methylscopolamine from human M2 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 438.45, ALogP 5.48, HBA 5, HBD 2, PSA 80.9, QED 0.53
Compound (SMILES): COc1ccc2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c2c1
InChIKey: XIQPDIUHKIOZOL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.39, ALogP 2.82, HBA 4, HBD 1, PSA 54.56, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CC2CCCO2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GBXSGEIAMQTWMD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 445.52, ALogP 4.36, HBA 8, HBD 0, PSA 74.53, QED 0.42
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCCC[C@H]2C(=O)N1
InChIKey: ZDTMGSSRQLKYTK-UGSOOPFHSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of recombinant human N-terminal His6-tagged EphA2 (N598 to R890 residues) expressed in baculovirus using poly-EY as substrate after 180 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 520.39, ALogP 4.56, HBA 7, HBD 2, PSA 88.61, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CCN2C[C@@H]3C[C@H]2CN3)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: NQVUICANYJFDGS-CQERKEQDSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 21.88 nM (pChEMBL 7.659999847412109)
Descriptors: MW 485.59, ALogP 3.23, HBA 9, HBD 1, PSA 80.57, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)s2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VQXBFPOCHKNAOT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 492, ALogP 6.1, HBA 8, HBD 0, PSA 65.3, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2cccc(Br)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JBJLDYOTZAKYCV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 531.41, ALogP 5.54, HBA 8, HBD 0, PSA 78.19, QED 0.26
Compound (SMILES): Cc1ccc(NC(=O)CCCCCC(=O)Nc2ccccc2N)cc1
InChIKey: WTKBRPXPNAKVEQ-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: HDAC enzyme inhibitionAssay: HDAC enzyme inhibition assays were performed using purified HDACs 1-10 essentially as described in Beckers et al., 2007, Int. J. Cancer., 121:1138-48 and Perez-Balado et al., 2007, J. Med. Chem., 50:2497-2505. Inhibition assays using nuclear extract were performed essentially as described in Herman et al., 2006, Nat. Chem. Biol., 2:551-558. Briefly, the purified HDACs or nuclear extract were incubated with an acetylated substrate in the absence of the compound to be assayed and with increasing concentrations of the compound. The rate of substrate deacetylation was measured under each condition, and half-maximal inhibitory concentration with regard to each HDAC was determined by standard means.
Measurement: IC50 = 66200 nM (pChEMBL 4.179999828338623)
Descriptors: MW 339.44, ALogP 4.1, HBA 3, HBD 3, PSA 84.22, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(C/C(=N/O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HRMKTZOBLPIBBW-GNVQSUKOSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 173.78 nM (pChEMBL 6.760000228881836)
Descriptors: MW 460.54, ALogP 4.67, HBA 9, HBD 1, PSA 97.89, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CCNC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JJPFEPQJBUBRFW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 147.91 nM (pChEMBL 6.829999923706055)
Descriptors: MW 484.56, ALogP 2.91, HBA 9, HBD 2, PSA 97.56, QED 0.4
Compound (SMILES): COc1cccc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NTDPWPKQOCPZDC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 588.84 nM (pChEMBL 6.230000019073486)
Descriptors: MW 505.58, ALogP 5.25, HBA 8, HBD 0, PSA 74.53, QED 0.28
Compound (SMILES): Cc1nc(C(N)=O)ccc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: WEEBXSDEOQNZPK-NLFFAJNJSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in microsomes using BMC as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.62, ALogP 4.67, HBA 7, HBD 1, PSA 89.93, QED 0.34
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(OCCCN5CCCC5)nc4)cc23)c1F
InChIKey: UJQYWQCKAHYIAY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 583.66, ALogP 5.15, HBA 7, HBD 2, PSA 117.28, QED 0.17
Compound (SMILES): COc1cc(OC)cc(N(C[C@H](O)CNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: PUCMKYWRDKWWQJ-ZMBIFBSDSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 476.58, ALogP 3.54, HBA 9, HBD 2, PSA 97.56, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: VFFSRBOFGPSKTB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.762 nM (pChEMBL 8.109999656677246)
Descriptors: MW 432.53, ALogP 4.19, HBA 8, HBD 1, PSA 91.32, QED 0.45
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccccc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GHWXUQIYJKZOLT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 451.53, ALogP 5.39, HBA 7, HBD 0, PSA 65.3, QED 0.33
Compound (SMILES): Cl.Clc1ccc2sc(CCCCN3CCC4CCCCC4C3)nc2c1
InChIKey: LLHIQLAPTLWBMG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D2 receptor by liquid scintillation counting method
Measurement: Ki = 1096.48 nM (pChEMBL 5.960000038146973)
Descriptors: MW 362.97, ALogP 5.78, HBA 3, HBD 0, PSA 16.13, QED 0.63
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(-c2ncco2)cc1
InChIKey: NIFGQHGFOUMQJN-KCWPFWIISA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human dopamine D2L receptor expressed in CHO cells coexpressing Galpha16 assessed as inhibition of dopamine-induced Ca2+ stimulation pre-incubated for 10 mins followed by dopamine challenge by Fluo-4AM based fluorometric analysis
Measurement: Ki = 676.08 nM (pChEMBL 6.170000076293945)
Descriptors: MW 539.63, ALogP 6.52, HBA 7, HBD 0, PSA 59.98, QED 0.19
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)c(OC(F)(F)F)c2)cc(OC)c1
InChIKey: RNUOMGDKVIMQSL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: IC50 = 1056 nM (pChEMBL 5.980000019073486)
Descriptors: MW 446.45, ALogP 4.03, HBA 6, HBD 2, PSA 85.89, QED 0.6
Compound (SMILES): COc1cc(OC)cc(N(CCn2cnnc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RUROKZDZIPBDNX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 123.03 nM (pChEMBL 6.909999847412109)
Descriptors: MW 456.51, ALogP 3.48, HBA 10, HBD 0, PSA 96.01, QED 0.35
Compound (SMILES): C[C@@H]1C[C@H](N)CN(c2ccncc2Nc2ncc3ccc(-c4c(F)cccc4F)nn23)C1
InChIKey: BYFQNMWZRKKFRI-CABCVRRESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: PIM Enzyme Assay: The assay for the determination of Pim activity is based on the formation of phosphorylated biotinylated-BAD peptide at the Serine 112 residue (S112) and employs HTRF (homogeneous time resolved fluorescence) technology to detect the product in a 96-well plate format. The phosphorylation of biotinylated-BAD (S112) peptide by full length recombinant Pim-1, Pim-2, or Pim-3 protein was detected with streptavidin:Allophycocyanin (APC) conjugate and a europium (Eu) labeled antibody directed against phosphorylated-BAD (S112). Excitation of Eu by a high energy laser light (337 nm) leads to a transfer of energy to the APC molecule, and results in an emission at 665 nm. The fluorescence is directly proportional to the amount of phosphorylated BAD peptide present in the reaction.Compounds were prepared in DMSO by conducting 3-fold serial dilutions to give a 10-point dosing curve having a high dose of 1 uM. A reference compound was included on each assay plate in order to validate that plate.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 435.48, ALogP 3.99, HBA 7, HBD 2, PSA 84.37, QED 0.5
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCN)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NHSCTFBEZPHZRZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 475.55, ALogP 2.74, HBA 9, HBD 2, PSA 120.42, QED 0.36
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnc(N(C)C)nc4)cc23)c1F
InChIKey: CNMJRJRTAYPAML-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 500.53, ALogP 3.75, HBA 7, HBD 2, PSA 120.94, QED 0.35
Compound (SMILES): COC[C@@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-BOXHHOBZSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 69.18 nM (pChEMBL 7.159999847412109)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31