lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CC[C@H]2c2nc(-c3cc(F)cc(F)c3)no2)c1
InChIKey: HGTNUOBQFYOFEQ-SFHVURJKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Intracellular Calcium Assay: Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 μg/mL G418, 100 U/mL penicillin, 100 μg/mL streptomycin and 10% heat inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into 384-well black clear bottom sterile plates (Greiner). The seeded plates are incubated overnight at 37° C. in 5% CO2. Human orexin-A as an agonist is prepared as 1 mM stock solution in MeOH:water (1:1), diluted in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/L and 20 mM HEPES for use in the assay at a final concentration of 3 nM. Antagonists are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates using DMSO followed by a transfer of the dilutions into in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/L and 20 mM HEPES. On the day of the assay, 50 μL of staining buffer (HBSS containing 1% FCS, 20 mM HEPES, NaHCO3: 0.375 g/L, 5 mM probenecid (Sigma) and 3 μM of the fluorescent calcium indicator fluo-4 AM (1 mM stock solution in DMSO, containing 10% pluronic) is added to each well. The 384-well cell-plates are incubated for 50 min at 37° C. in 5% CO2 followed by equilibration at rt for 30 min before measurement. Within the Fluorescent Imaging Plate Reader (FLIPR Tetra, Molecular Devices), antagonists are added to the plate in a volume of 10 μL/well, incubated for 120 min and finally 10 μL/well of agonist is added. Fluorescence is measured for each well at 1 second intervals, and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 3 nM orexin-A with vehicle in place of antagonist.
Measurement: IC50 = 2320 nM (pChEMBL 5.630000114440918)
Descriptors: MW 422.39, ALogP 3.49, HBA 7, HBD 0, PSA 89.94, QED 0.5
Compound (SMILES): Cc1cc(C#N)ccc1NC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: NNHRTRASNYRKSM-JCNLHEQBSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 385.48, ALogP 4.17, HBA 6, HBD 2, PSA 94.69, QED 0.55
Compound (SMILES): O=C1NCc2c(Oc3ccc(NC(=O)c4cnn(-c5ccccc5)c4C(F)(F)F)cc3F)ccnc2N1
InChIKey: NDMHWVQYGCWZAS-UHFFFAOYSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Enzyme Assay: The kinase assay was carried out as 384-well FlashPlate assay. As test plates 384-well streptavidine coated FlashPlate microtitre plates from Perkin Elmer (USA) were used. The components of the kinase reaction were pipetted into the assay plate. 4.5 nM of GST tagged human recombinant RON kinase (Life technologies), 500 nM of biotinylated peptide substrate RDILDREYYSVQQHRH-amide (autophosphorylation site derived peptide substrate, custom-made) and 2 μM of ATP (with 0.5 μCi of <33>P-ATP/well) were incubated in a total volume of 50 μl (50 mM of HEPES, 5 mM of MgCl2, 2 mM of DTT, 0.1% of BSA, 0.01% Igepal®CA630, 1% DMSO, pH 7.5) in the presence or absence of test substance (10 concentrations) at 22 [deg.] C. for 30 min. The reaction was stopped using 50 μl of 200 mM EDTA solution. After incubation for a further 80 min at room temperature, the supernatants were removed by suction, and the wells were washed three times with 100 μl of 0.9% NaCl solution each time.
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 512.42, ALogP 5.1, HBA 6, HBD 3, PSA 110.17, QED 0.32
Compound (SMILES): CC[C@H](CN1CC[C@H](CNC(=O)c2ccc3cc(Cl)ccc3c2)N[C@H](Cc2cc(Cl)cc(Cl)c2Cl)C1=O)c1ccccc1
InChIKey: JCYVMKXBRXUZFL-IIBYOBAOSA-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 < 100 nM (pChEMBL 7)
Descriptors: MW 657.47, ALogP 8.18, HBA 3, HBD 2, PSA 61.44, QED 0.18
Compound (SMILES): CCc1nnc2c(C(N)=O)c(Nc3ccc(N4CCNCC4)cc3OC)nc(Cc3c(Cl)cccc3Cl)n12
InChIKey: QZYMNDLNGOMMHJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Enzyme Inhibition Assay: ALK kinase assays were conducted with the indicated final concentrations unless otherwise specified. In 384 well black plates (Axygen), 8 ul of compound (2% DMSO) was incubated with 8 ul Lck-peptide substrate (0.5 uM, biotin-Ahx-GAEEEIYAAFFA-COOH) and 8 ul of a mixture of ALK (3 nM, Millipore) and ATP (50 uM) in reaction buffer (50 mM Hepes, pH 7.4; 10 mM MgCl2; 2 mM MnCl2; 0.1 mM sodium orthovanadate; 0.01% BSA and 1 mM DTT (added fresh before assay) for 1 h at room temperature. Reactions were then quenched by the addition of 30 ul quench solution (streptavidin-allophycocyanin and Europium-cryptate PT66 monoclonal antibody in 40 mM Hepes, pH 7.4; 480 mM KF; 66 mM EDTA; 0.01% Tween-20; and 0.1% BSA) at room temperature. Plates were read 1 h after quenching on an Envision Multilaber Reader and IC50 values were calculated using a sigmoidal fit of the concentration/inhibition response curves. These values were converted to apparent Ki values.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 555.47, ALogP 3.85, HBA 9, HBD 3, PSA 122.7, QED 0.3
Compound (SMILES): CC1CN(c2ccncc2Nc2ncc3ccc(-c4c(F)cccc4F)nn23)C(C)CN1
InChIKey: JCHKNLLUGJTBFB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
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 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 435.48, ALogP 4, HBA 7, HBD 2, PSA 70.38, QED 0.51
Compound (SMILES): Cn1cc(-c2ccc(F)cc2)cc(C(=O)Nc2ccc(Oc3ccncc3-c3cccnc3)c(F)c2)c1=O
InChIKey: ZKBIOFONGJWAFB-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 30 mins by HTRF assay
Measurement: IC50 = 106.4 nM (pChEMBL 6.96999979019165)
Descriptors: MW 510.5, ALogP 5.83, HBA 6, HBD 1, PSA 86.11, QED 0.31
Compound (SMILES): O=C(O)Cc1cnc(C2=CCN(C(=O)Nc3ccc(C(F)(F)F)cc3)CC2)c(Cl)c1
InChIKey: QPSYEDNBKVXJEQ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Capsaicin-Based Assay: Two days prior to performing this assay, cells are seeded in poly-D-lysine-coated 96-well clear-bottom black plates (50,000 cells/well) in growth media containing 5 μM PonA (commercially available from Invitrogen) to induce expression of TRPV1. On the day of the assay, the plates are washed with 0.2 mL 1× Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 1 mM CaCl2 and 20 mM HEPES, pH 7.4, and cells are loaded using 0.1 mL of wash buffer containing Fluo-4 (3 μM final). After one hour, the cells are washed twice with 0.2 mL of wash buffer and resuspended in 0.1 mL of wash buffer. The plates are transferred to a FLIPR for assay. 50 μL of test compound diluted with assay buffer (1× Hank's Balanced Salt Solution containing 1 mM CaCl2 and 20 mM HEPES, pH 7.4) are added to the cell plates and incubated for 2 min. The final concentration of the compound is adjusted to range from about 50 picoM to about 3 μM. Human TRPV1 is activated by the addition of 50 μL of capsaicin (400 nM), and the plates are incubated for an additional 3 min.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 439.82, ALogP 4.7, HBA 3, HBD 2, PSA 82.53, QED 0.72
Compound (SMILES): NS(=O)(=O)c1ccc(OCc2cn(-c3ccc(O)cc3)nn2)cc1
InChIKey: JYGYLWAUBIYKPU-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 pre-incubated for 15 mins by stopped flow carbon dioxide hydrase assay
Measurement: Ki = 92.8 nM (pChEMBL 7.03000020980835)
Descriptors: MW 346.37, ALogP 1.2, HBA 7, HBD 2, PSA 120.33, QED 0.72
Compound (SMILES): COc1ccc(F)c(C(C)NC(=O)c2ccc(-c3cn[nH]c3)cc2OC)c1
InChIKey: MVTQJLVXODOUEE-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity.
Measurement: IC50 = 19.2 nM (pChEMBL 7.71999979019165)
Descriptors: MW 369.4, ALogP 3.72, HBA 4, HBD 2, PSA 76.24, QED 0.69
Compound (SMILES): Cc1cc(-c2n[nH]c3ccc(C(=O)NC4CCCC(CO)(Cc5ccc(F)cc5)C4)cc23)ccn1
InChIKey: PRIQHVHPBJKELZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: Active ERK2 (aERK) Assay: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 14 μl of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 357.2 nM (pChEMBL 6.449999809265137)
Descriptors: MW 472.56, ALogP 4.97, HBA 4, HBD 3, PSA 90.9, QED 0.37
Compound (SMILES): CC(CO)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cc3)c2)c2cncc(F)c21
InChIKey: VYFKLOIGTHUTMY-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: HTRF Assay: Isolated TRK Enzyme assays use the HTRF KinEASE-TK kit (Cisbio Cat#62TK0PEJ) with recombinant His-tagged cytoplasmic domains of each TRK receptor sourced from Invitrogen (see table below). This activity-assay measures the phosphorylation of tyrosine residues within a substrate from the HTRF kit which has been validated by Cisbio for a variety of tyrosine kinases including the TRK receptors.Assay Details: Invitrogen Amino FAC FAC Assay ReactionTarget Cat# acids enzyme ATP TimeTRKA PV3144 aa 441-4 nM 40 uM 35 min (NTRK1) 796 TRKB PV3616 aa 526-1 nM 1.4 uM 40 min (NTRK2) 838 TRKC PV3617 aa 510- 10 nM 15 uM 30 min (NTRK3) 8250.5 mM stock solutions of test compounds are prepared and serially diluted in 100% DMSO. A standard curve using the compound of Example 135 disclosed in WO2005/116035 of 150 uM is also prepared on each test plate. High percentage effect (HPE) is defined by 150 uM.
Measurement: IC50 = 20.7 nM (pChEMBL 7.679999828338623)
Descriptors: MW 466.9, ALogP 4.19, HBA 6, HBD 2, PSA 97.11, QED 0.4
Compound (SMILES): NCCCn1c2ccccc2c2ccnc(CN(CCCN3CCNC(=O)C3)[C@H]3CCCc4cccnc43)c21
InChIKey: MBBNVMFTQPOESS-NDEPHWFRSA-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 525.7, ALogP 3.63, HBA 7, HBD 2, PSA 92.31, QED 0.33
Compound (SMILES): CC(C)(C)OC(=O)N1C[C@@H](Oc2ccc(-c3ccc(Cl)cc3)cc2)C[C@H]1C(=O)N[C@@H](Cc1ccc(OCc2ccc([N+](=O)[O-])cc2)cc1)C(=O)NS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
InChIKey: SJOBEKGTCCUNMS-LUYPYDKDSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of 5-FAM-QEDIIRNIARHLAQVGDSMDRSIPPG binding to Mcl-1 (unknown origin) preincubated for 30 mins followed by FAM-labeled peptide addition measured after 20 mins by fluorescence polarization assay
Measurement: Ki = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 934.81, ALogP 8.05, HBA 12, HBD 2, PSA 226.62, QED 0.08
Compound (SMILES): CCNC(=O)Nc1ccc(-c2nc(N3CCOC[C@@H]3C)nc3c2C(=O)N(CC)CC(C)(C)O3)cc1
InChIKey: FINNGPDNYBZHBN-INIZCTEOSA-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 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 482.59, ALogP 3.14, HBA 7, HBD 2, PSA 108.92, QED 0.67
Compound (SMILES): CCOc1ccc(C[C@@H](NC(=O)c2ccccc2)C(=O)N[C@@H](Cc2csc3ccccc23)C(=O)NCc2ccc(CN)cc2)cc1
InChIKey: XQQTZKDEZFNLED-SAIUNTKASA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: In Vitro Inhibition Assay: Plasma kallikrein inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stiirzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human plasma kallikrein (Protogen) was incubated at 37° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 634.8, ALogP 5.14, HBA 6, HBD 4, PSA 122.55, QED 0.13
Compound (SMILES): CN1CC[C@H](c2c(O)cc(O)c3c(=O)cc(-c4ccc(C(F)(F)F)cc4)oc23)[C@H](O)C1
InChIKey: DVFJGRYENKMQBH-SUMWQHHRSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin A using histone H1 as substrate after 10 mins by [gamma-32P]ATP based binding assay
Measurement: IC50 = 301.9 nM (pChEMBL 6.519999980926514)
Descriptors: MW 435.4, ALogP 3.67, HBA 6, HBD 3, PSA 94.14, QED 0.57
Compound (SMILES): CS(=O)(=O)Nc1cccnc1OCC(=O)NCC(O)CN1CCc2ccccc2C1
InChIKey: CYIBKTIUIDAHKJ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 434.52, ALogP 0.37, HBA 7, HBD 3, PSA 120.86, QED 0.52
Compound (SMILES): CCOCCc1cc2cnc(Nc3ccc(N4CCNCC4)cc3)nc2n(C2CCCC2)c1=O
InChIKey: RNJBKGOBEDAWSH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of Cdk4/Cyclin D (unknown origin) using retinoblastoma protein substrate and [gamma32P]ATP incubated for 15 mins by beta plate counter based assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 462.6, ALogP 3.64, HBA 8, HBD 2, PSA 84.31, QED 0.49
Compound (SMILES): CC(C)COc1ncnc2[nH]cc(/C=C/C#N)c12
InChIKey: SPEMUMBPRQTTAA-ONEGZZNKSA-N
Target: TAK1/TAB1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O43318
Assay: Inhibition of kinase tracer-236 binding to full length recombinant human His-tagged TAK1-TAB1 expressed in baculovirus by FRET assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 242.28, ALogP 2.53, HBA 4, HBD 1, PSA 74.59, QED 0.84
Compound (SMILES): Cc1cccc2c(N[C@@H](C)c3ccc(NC(=O)c4ccc(Cl)nc4)cc3)nc(N(C)C)nc12
InChIKey: QLOFWZQHBRWCBS-INIZCTEOSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 3951 nM (pChEMBL 5.400000095367432)
Descriptors: MW 460.97, ALogP 5.48, HBA 6, HBD 2, PSA 83.04, QED 0.37
Compound (SMILES): O=C(COc1ccc(F)cc1)NCC(O)CN1CCc2ccccc2C1
InChIKey: VCJHGNUPZNBBQI-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 358.41, ALogP 1.74, HBA 4, HBD 2, PSA 61.8, QED 0.79
Compound (SMILES): CCNCc1cncc(-c2cccc3[nH]nc(-c4nc5c(F)cc(F)cc5[nH]4)c23)c1C
InChIKey: VWQIQPRBMMSYCE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/G1/S-specific cyclin-E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4/cyclin E (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 418.45, ALogP 4.86, HBA 4, HBD 3, PSA 82.28, QED 0.38
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3cccnc3Cl)cc2)c2ccccc2n1
InChIKey: CTMSGNYEINNMPK-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 > 2984 nM (pChEMBL 5.525000095367432)
Descriptors: MW 418.89, ALogP 4.58, HBA 6, HBD 3, PSA 91.83, QED 0.4
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)nc(NC3CCN(Cc4ccccc4)CC3)nc2c1
InChIKey: ZQCONYAPBNCDPT-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 > 2175 nM (pChEMBL 5.663000106811523)
Descriptors: MW 574.7, ALogP 7.02, HBA 6, HBD 3, PSA 82.18, QED 0.18
Compound (SMILES): OC(COc1cccc(-c2cccnc2F)c1)CN1CCc2ccccc2C1
InChIKey: FAIPIJNYKDXJMJ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 378.45, ALogP 3.69, HBA 4, HBD 1, PSA 45.59, QED 0.66
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)C4CCN(Cc5ccc(F)c(F)c5)CC4)cc3)nc(N(C)C)nc2c1
InChIKey: ZSNPUIWMTSJNFC-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 544.65, ALogP 5.75, HBA 6, HBD 2, PSA 73.39, QED 0.29
Compound (SMILES): CCN(CC)c1nc(NCc2ccc(NC(=O)c3ccc(F)cc3)cc2)c2cc(C)ccc2n1
InChIKey: JHFRHTLCCWDGCE-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 492 nM (pChEMBL 6.309999942779541)
Descriptors: MW 457.55, ALogP 5.79, HBA 5, HBD 2, PSA 70.15, QED 0.35
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3ccc(Br)cc3)cc2)c2ccc(C)cc2n1
InChIKey: DLPHGOYOYJSYIG-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 476.38, ALogP 5.61, HBA 5, HBD 3, PSA 78.94, QED 0.34
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)nc(N(C)CCO)nc2c1
InChIKey: NKYVJKPVWKBETD-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 459.53, ALogP 4.37, HBA 6, HBD 3, PSA 90.38, QED 0.36
Compound (SMILES): CC(C)C[C@H]1CNC(=O)c2cc3c[nH]/c(=N/c4ccc(N5CCN(C)CC5)cn4)nc3n21
InChIKey: LOTLHAUOJRZXNQ-SFHVURJKSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Kinase Enzymatic Assay: Kinase enzymatic reactions were performed in 384-well microplates using a 12-channel Caliper LabChip instrument as a detection device. The enzymatic phosphorylation of a peptide results in a change in net charge, enabling electrophoretic separation of product from substrate. As substrate and product are separated, two peaks of fluorescence are observed. Change in the relative fluorescence intensity of the substrate and product peaks is the parameter measured, reflecting enzyme activity. In the presence of an inhibitor, the ratio between product and substrate is altered. The signal of the product decreases, while the signal of the substrate increases.For the measurement of CDK2/cyclinE activity, enzyme (0.22 nM) was incubated with 100 mM ATP and the phosphoacceptor substrate peptide (1 mM) for one hour. For the measurement of CDK4/CyclinD activity, enzyme (0.85 nM) was incubated with 200 mM ATP and the phosphoacceptor substrate peptide (1 mM) for three hours. Potential inhibitor compounds (as HCl salts) were tested using 12-point dose response curves in single point at the Km for ATP.
Measurement: IC50 = 50500 nM (pChEMBL 4.300000190734863)
Descriptors: MW 434.55, ALogP 2.07, HBA 7, HBD 2, PSA 94.44, QED 0.66
Compound (SMILES): CN1Cc2cc(ccc2S(=O)(=O)C2CC2)NC(=O)CCc2cc(ccc2OCC(F)F)[C@@H](Nc2ccc3c(N)ncc(F)c3c2)C1=O
InChIKey: DCIOQBFAYLXHBY-WJOKGBTCSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 37 degC
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 667.71, ALogP 5.23, HBA 8, HBD 3, PSA 143.72, QED 0.24
Compound (SMILES): NCCCNc1cc(-c2cncc(NCC3CCOCC3)c2)c(Cl)cn1
InChIKey: TUIHLGIQAFUWDM-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of recombinant human full length C-terminal His6-tagged CDK9/cyclin T1 expressed in baculovirus infected Sf21 insect cells using 5TAMRA-cdk7tide as substrate after 4.5 hrs by IMAP assay
Measurement: IC50 = 1858 nM (pChEMBL 5.730000019073486)
Descriptors: MW 375.9, ALogP 3.4, HBA 6, HBD 3, PSA 85.09, QED 0.61
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cccc(O)c4)c4c(N)ncnc43)n(C)c(=O)c12
InChIKey: IWMPEWUTZPNURX-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
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 < 100 nM (pChEMBL 7)
Descriptors: MW 412.45, ALogP 2.99, HBA 8, HBD 2, PSA 111.85, QED 0.47
Compound (SMILES): Cl.O=C(O)[C@]1(Cc2cccc(Nc3nccs3)n2)CC[C@@H](Oc2cccc(F)c2F)CC1
InChIKey: UXKBXDMNTYISCK-PGIBDOGXSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human full-length N-terminal GST-tagged Aurora B/His-tagged INCENP (803 to 916 residues) using kemptide as substrate and [gamma33P]ATP after 45 mins by liquid scintillation counting method
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 445.49, ALogP 5.2, HBA 6, HBD 2, PSA 84.34, QED 0.52
Compound (SMILES): CN1CC[C@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4)oc23)[C@H](O)C1
InChIKey: PGWURUYAKNYOPM-SUMWQHHRSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin A using histone H1 as substrate after 10 mins by [gamma-32P]ATP based binding assay
Measurement: IC50 = 196 nM (pChEMBL 6.710000038146973)
Descriptors: MW 367.4, ALogP 2.65, HBA 6, HBD 3, PSA 94.14, QED 0.64
Compound (SMILES): O=C(Cn1ccc2cnc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)nc21)N1CCOCC1
InChIKey: OZDOMCSPERFISZ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 527.63, ALogP 2.76, HBA 8, HBD 1, PSA 92.95, QED 0.38
Compound (SMILES): CCn1c(Cn2nc(-c3ccc4nc(NC(C)=O)sc4c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: NSYSGNDISDECIU-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human 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 < 100000 nM (pChEMBL 4)
Descriptors: MW 524.61, ALogP 4.34, HBA 10, HBD 2, PSA 133.61, QED 0.34
Compound (SMILES): Cn1ccc2ccc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)nc21
InChIKey: LCAFUBIHLJBTGT-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 413.52, ALogP 4.04, HBA 5, HBD 1, PSA 50.52, QED 0.52
Compound (SMILES): CC1(C)C[C@H](Nc2cc(N[C@@H]3C[C@@H](COS(N)(=O)=O)[C@@H](O)C3)ncn2)c2ccccc21
InChIKey: DNNKIUMVIDXECX-DACLVMHWSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 447.56, ALogP 2.08, HBA 8, HBD 4, PSA 139.46, QED 0.51
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccn[nH]3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: MVRRILMCOGDYKT-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
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 462.52, ALogP 3.77, HBA 8, HBD 2, PSA 120.3, QED 0.41
Compound (SMILES): CN(C)S(=O)(=O)c1ccccc1OCC(=O)NCC(O)CN1CCc2ccccc2C1
InChIKey: DHMXPMYEMYHGNF-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 447.56, ALogP 0.85, HBA 6, HBD 2, PSA 99.18, QED 0.59
Compound (SMILES): OC(COc1ccc(OCc2ccccc2)cc1)CN1CCc2ccccc2C1
InChIKey: ZFHVQTAPWPBIPE-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 389.5, ALogP 4.06, HBA 4, HBD 1, PSA 41.93, QED 0.63
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(C3(C(=O)O)CC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: RFKOYFYQZZFWKX-ADXZGYQBSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human TF-factor 7a using factor 10 as substrate at 37 degC
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 611.67, ALogP 5.86, HBA 7, HBD 4, PSA 146.88, QED 0.22
Compound (SMILES): N#Cc1c(N)ncnc1N[C@@H](CO)c1nn2cccc2c(=O)n1-c1ccccc1
InChIKey: JBHVOCPTEPOSAI-AWEZNQCLSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of full length recombinant human N-terminal His6-tagged PI3K p110delta/human p85alpha expressed in baculovirus infected sf21 cells using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 388.39, ALogP 0.87, HBA 10, HBD 3, PSA 147.15, QED 0.46
Compound (SMILES): COCC[C@@H]1C[C@H]1c1cncc(N2CCCNCC2)c1
InChIKey: FTYHMMVUGBYQCJ-CZUORRHYSA-N
Target: Neuronal acetylcholine receptor; alpha2/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12389
Assay: Displacement of [3H]epibatidine from rat alpha2beta2 nAChR by liquid scintillation counting
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 275.4, ALogP 2.02, HBA 4, HBD 1, PSA 37.39, QED 0.89
Compound (SMILES): Cc1ncc2ccc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)cn12
InChIKey: KXXZKVYXBFLEEU-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 413.52, ALogP 4.11, HBA 5, HBD 1, PSA 50, QED 0.52
Compound (SMILES): O=S(=O)(C1CC1)N1CCN(c2nc(N3CCOCC3)ncc2Br)CC1
InChIKey: MAEVHSVRMUAWLW-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of BRC/ABL1 (unknown origin) after 40 mins by ADP-Glo assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 432.34, ALogP 0.69, HBA 7, HBD 0, PSA 78.87, QED 0.69
Compound (SMILES): N#Cc1ccccc1-c1cccc(OCC(O)CN2CCc3ccccc3C2)c1
InChIKey: AMSKEMVZDWBSOE-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 384.48, ALogP 4.02, HBA 4, HBD 1, PSA 56.49, QED 0.7
Compound (SMILES): O=C(NCC(O)CN1CCc2ccccc2C1)c1cccc(CN2CCNCC2)c1
InChIKey: VRTIHHGJSVOSCF-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 408.55, ALogP 1.24, HBA 5, HBD 3, PSA 67.84, QED 0.64
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cccc(O)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: ABHYRAOZUATJPX-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/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 > 10000 nM (pChEMBL 5)
Descriptors: MW 492.51, ALogP 4.58, HBA 8, HBD 2, PSA 111.85, QED 0.37
Compound (SMILES): CN(Cc1ccccc1)c1cc(N[C@@H]2C[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)ncn1
InChIKey: WHCPURSXXHCTPI-DTDBQYNISA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.5, ALogP -0.14, HBA 9, HBD 4, PSA 150.9, QED 0.45
Compound (SMILES): c1ccc(NC2=NC[C@@]3(CN4CCC3CC4)O2)nc1
InChIKey: NWOGQPOGFKBIMN-AWEZNQCLSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Agonist activity at alpha4beta2 nAChR (unknown origin) assessed as increase in calcium influx measured for 2 mins by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 258.32, ALogP 1.34, HBA 5, HBD 1, PSA 49.75, QED 0.83
Compound (SMILES): Cn1cc2cc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)ccc2n1
InChIKey: RJOCEZNWLGCLIW-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 413.52, ALogP 4.04, HBA 5, HBD 1, PSA 50.52, QED 0.52
Compound (SMILES): C[C@@H]1CC(=O)Nc2ccc(S(=O)(=O)C3CC3)c(c2)CN(C)C(=O)[C@H](Nc2ccc3c(N)ncc(F)c3c2)c2ccc(OCC(F)F)c1c2
InChIKey: UWAQLEGUXYPPDC-ZUQCGGBESA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 37 degC
Measurement: Ki = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 681.74, ALogP 5.79, HBA 8, HBD 3, PSA 143.72, QED 0.22
Compound (SMILES): Cc1ccc(Oc2nc3cc(-c4ccc(N5CCOCC5)cc4)c(Cl)cc3[nH]2)cc1P(=O)(O)O
InChIKey: IXXQMMAJDZTDBZ-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54619
Assay: Activation of full length human recombinant AMPK alpha1/beta1/gamma1 expressed in baculovirus infected sf21 cells using SAMS peptide substrate after 30 mins in presence of [33P]ATP by TopCount analysis
Measurement: EC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 499.89, ALogP 4.62, HBA 5, HBD 3, PSA 107.91, QED 0.34
Compound (SMILES): CC1Cc2ccccc2CN1CC(O)COc1cccc(-c2ccc3ncn(C)c3c2)c1
InChIKey: UBUZZLGKOCVLAB-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 427.55, ALogP 4.43, HBA 5, HBD 1, PSA 50.52, QED 0.49
Compound (SMILES): CN1CCC(n2cnc3ccc(-c4cccc(OCC(O)CN5CCc6ccccc6C5)c4)cc32)C1
InChIKey: NLYZVVRPHVZTST-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 482.63, ALogP 4.38, HBA 6, HBD 1, PSA 53.76, QED 0.42
Compound (SMILES): OCc1ccc(-c2cccc(OCC(O)CN3CCc4ccccc4C3)c2)cc1
InChIKey: QMTQAHOVVREHPQ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 389.5, ALogP 3.64, HBA 4, HBD 2, PSA 52.93, QED 0.65
Compound (SMILES): N=C(N)Nc1ccc(C(=O)Nc2ccc(C[C@H](NC(=O)[C@@H]3CCCN3S(=O)(=O)c3ccccc3)C(=O)O)cc2)cc1
InChIKey: RLVWHKYTSBZABY-ZEQRLZLVSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 578.65, ALogP 2.21, HBA 6, HBD 6, PSA 194.78, QED 0.16
Compound (SMILES): CN(c1cccc(OCC(=O)NCC(O)CN2CCc3ccccc3C2)c1)S(C)(=O)=O
InChIKey: GFKDIZRIYPKLBK-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 447.56, ALogP 1, HBA 6, HBD 2, PSA 99.18, QED 0.6
Compound (SMILES): CCC(=O)O[C@@H]1[C@@H]2[C@@H](OC(C)=O)[C@@]34CO[C@@](C)([C@H](OC(C)=O)[C@@]2(OC(C)=O)C[C@@H]1C)[C@@H]3[C@@H](C(C)(C)OC(C)=O)C=CC4=O
InChIKey: CXJDPEXIUOUAII-OQLYQZTESA-N
Target: Kir3.1/Kir3.4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P48549
Assay: Inhibition of GTPgammaS-induced activation of GIRK1/4 (unknown origin) expressed in HEK293 cells assessed as decrease in channel current after 2 mins at -40 mV holding potential by automated patch-clamp electrophysiology assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 606.67, ALogP 2.63, HBA 12, HBD 0, PSA 157.8, QED 0.31
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4C(F)(F)F)ccc3o2)cc1)c1ccccc1C(F)(F)F
InChIKey: ZBFJZBKUCXPCTN-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/GroES expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 20 to 40 mins by fluorescence based assay
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 641.57, ALogP 7.13, HBA 6, HBD 2, PSA 118.37, QED 0.18
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3ccc(Cl)cc3)cc2)c2cc(C)cc(C)c2n1
InChIKey: HIKINKJOKJCOLS-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 756 nM (pChEMBL 6.119999885559082)
Descriptors: MW 445.95, ALogP 5.81, HBA 5, HBD 3, PSA 78.94, QED 0.35
Compound (SMILES): Cn1ccc(C(=O)Nc2cccc(OCC(O)CN3CCc4ccccc4C3)c2)n1
InChIKey: OJTORCHWEVNHNC-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 406.49, ALogP 2.47, HBA 6, HBD 2, PSA 79.62, QED 0.63
Compound (SMILES): Cc1ncc2sc(C(=O)N3CCCC3c3ccccc3)nn12
InChIKey: CQZLZZDJBYTSDH-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of Alexa647 tracer binding to full length recombinant human His-tagged CDK8/cyclin C expressed in Baculovirus expression system preincubated for 20 mins followed by tracer addition and incubated in dark for 60 mins by FRET-based Lanthascreen assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 312.4, ALogP 3.08, HBA 5, HBD 0, PSA 50.5, QED 0.73
Compound (SMILES): COCC[C@@H]1C[C@H]1c1cncc(N2C[C@@H]3C[C@H]2CN3)c1
InChIKey: NRUGCGUIOWHUGI-SHPPOPEUSA-N
Target: Neuronal acetylcholine receptor; alpha2/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12389
Assay: Displacement of [3H]epibatidine from rat alpha2beta2 nAChR by liquid scintillation counting
Measurement: Ki = 43.1 nM (pChEMBL 7.369999885559082)
Descriptors: MW 273.38, ALogP 1.77, HBA 4, HBD 1, PSA 37.39, QED 0.89
Compound (SMILES): COc1ccc2cc1[C@H](C)CN(C)C(=O)Nc1ccc(S(=O)(=O)C3CC3)c(c1)CN(C)C(=O)C2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: DRLAOAUSFABNAU-MFUYNUFSSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 25 degC
Measurement: Ki = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 660.77, ALogP 5.29, HBA 8, HBD 3, PSA 146.96, QED 0.26