lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(C(C)Nc2nc(NC3CC3)n3ncc(/C=C4\NC(=O)NC4=O)c3n2)nc1
InChIKey: FFHKWYQJRPAXLG-CHHVJCJISA-N
Target: Casein kinase II subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P67870
Assay: Inhibition Assay: Test compounds dissolved and diluted in DMSO (2 μl) were added to a reaction mixture comprising 10 μl of 5× Reaction Buffer (40 mM MOPS pH 7.0, 5 mM EDTA), 10 μl of recombinant human PIM2 solution (4 ng PIM-2 dissolved in dilution buffer (20 mM MOPS pH 7.0; EDTA 1 mM; 5% Glycerol; 0.01% Brij 35; 0.1%; 0.1% 2-mercaptoethanol; 1 mg/ml BSA)) and 8 ul of water. Reactions were initiated by the addition of 10 ul of ATP Solution (49% (15 mM MgCl2; 75 uM ATP) 1% ([γ-33P]ATP: Stock 1 mCi/100 μl; 3000 Ci/mmol (Perkin Elmer)) and 10 ul of substrate peptide solution (RSRSSYPAGT (SEQ ID NO.: 6), dissolved in water at a concentration of 1 mM), Reactions were maintained for 10 min at 30° C. The reactions were quenched with 100 ul of 0.75% Phosphoric acid, then transferred to and filtered through a Phosphocellulose filter plate (Millipore, MSPH-N6B-50). After washing each well 4 times with 0.75% Phosphoric acid, scintillation fluid (20 uL) was added to each well and the resid
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 419.45, ALogP 1.76, HBA 9, HBD 4, PSA 138.23, QED 0.35
Compound (SMILES): CC(C)(COC(=O)N1CC[C@@H](C#N)[C@H](n2cc(C(N)=O)c(Nc3ccc(F)cc3)n2)C1)n1cccn1
InChIKey: IIOSKYJCFFGDFH-OXJNMPFZSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Biochemical HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 μL of 1.11× enzyme and 1.11× substrate in 1× assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 μL of 10×ATP in 1× assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at ambient temperature for 120 minutes. At the end of the incubation, 20 μL of 2× stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction. Plates were shaken and centrifuged and then incubated 60 minutes at ambient temperature and then read on a Perkin Elmer Envision (λex=337 nm, λem=665 and 615 nm, TRF delay time=20 μs). HTRF signal=10,000*665 nm reading/615 nm reading.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 494.53, ALogP 3.02, HBA 9, HBD 2, PSA 144.09, QED 0.51
Compound (SMILES): O=C(NCCOC(F)(F)F)c1ccc2cc(Oc3ccc(C(F)(F)F)cn3)ccc2n1
InChIKey: RIVVRINDGCXJJO-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FRET-Based Membrane Potential Assay: Two days prior to the experiment, frozen HEK293 cells stably expressing recombinant human Nav1.7 were quickly thawed and plated at 25,000 cells/well in growth medium [DMEM (Invitrogen #11965) with 10% HI FBS (Invitrogen #10082), 2 mM glutamine, 100 units/mL penicillin, 0.1 mg/mL streptomycin (PSG, Sigma #G1146), and 500 ug/mL Geneticin (Invitrogen #10131)] in black-walled, clear-bottom 384-well poly-D-lysine-coated assay plates (Greiner Bio-One, Frickenhausen, Germany) and incubated in a humidified 5% CO2 incubator at 37° C. On the day of the assay, medium was removed by aspiration, and cells were washed with assay buffer [HBSS (Invitrogen, Carlsbad, Calif.) containing 20 mM HEPES (Invitrogen, Carlsbad, Calif.)]. After washing, 30 uL assay buffer containing the fluorescent voltage-sensor probe CC2-DMPE (Invitrogen, Carlsbad, Calif.) at 20 uM and 0.01% pluronic F-127 (Invitrogen, Carlsbad, Calif.) was added to the cells. Cells were incubated for 40 minutes at room temperature in the dark. Following the incubation, the cells were washed and 30 uL assay buffer containing 2.5 uM DiSBAC2(3) substrate (Invitrogen, Carlsbad, Calif.) and 0.5 mM VABSC-1 (Invitrogen, Carlsbad, Calif.) was added to the cells. The cells were incubated for 90 minutes at room temperature in the dark. Fluorescence readings were made using a FLIPR TETRA (Molecular Devices, Sunnyvale Calif.) equipped with voltage-sensor probe optics. At the start of each experiment the optimal (EC80) concentration of depolarizing agent (veratridine) was determined by testing a dilution curve of assay buffer containing veratridine (Sigma-Aldrich, St. Louis, Mo.) and 1 mg/mL scorpion venom (SVqq, from Leiurus quinquestriatus; Sigma-Aldrich, St. Louis, Mo.). Compounds were dissolved in dimethyl sulfoxide, and 8-point, 1:3 dilution concentration-response curves were prepared in duplicate in dimethyl sulfoxide, followed by preparation of 0.8 uL/well daughter plates of the dilutions. Test compounds in the daughter plate were diluted to (Ë¿3x) solutions in assay buffer immediately before assaying. Using the FLIPR TETRA, 20 uL of the (3x) compound solutions were first added to the cells, then 20 uL of depolarizing solution (3xEC80 veratridine+SVqq) were added 3 minutes later to activate the channel. Changes in fluorescence were measured at wavelengths of 440-480 nm and 565-625 nm over the course of the experimental run. Membrane depolarization was expressed as a ratio of the maximum F440-480 nm/F565-625 nm reading above average baseline F440-480 nm/F565-625 nm reading. IC50 values were calculated from curve fits of the ratio data using a four-parameter logistic Hill equation (Accelrys Assay Explorer 3.3 Client, Accelrys, San Diego, Calif.) with percent inhibition plotted against compound concentration.
Measurement: IC50 = 3290 nM (pChEMBL 5.480000019073486)
Descriptors: MW 445.32, ALogP 4.71, HBA 5, HBD 1, PSA 73.34, QED 0.44
Compound (SMILES): C[C@H](NC(=O)N(C)C)c1ccc(OC2CCN(c3ccc(OCC4CC4)cc3)C2)cc1
InChIKey: GPOQJWAPBBVCDT-VEXWJQHLSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/ml BSA, 3.75 mM reduced L-glutathione, 15 U/ml lactate dehydrogenase, 0.5 mM phosphoenolpyruvate, 15 U/ml pyruvate kinase, compounds at different concentrations at final DMSO concentrations of 1%.The enzymatic reaction is then started by addition of a mixture of NADH, acetyl Coenzyme A (both 200 μM f.c.) and ATP (500 uM f.c.). The decrease of the optical density (slope S) is then determined at 25° C. at a wavelength of 340 nm over 15 minutes in a spectrophotometric reader.
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 423.56, ALogP 4.47, HBA 4, HBD 1, PSA 54.04, QED 0.68
Compound (SMILES): Cc1nc2cnc3cc(F)c(-c4ccc(Oc5ncccn5)cc4Cl)cc3c2n1C1CCS(=O)(=O)CC1
InChIKey: LIPYYLYUPRIGII-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Radioactive Binding Assay: The radioactive filter binding assay is standardized using recombinant human activated BRAF (V599E) kinase (Cat No. 14-557) and kinase dead MEK1 (K97R) (Cat No. 14-737) procured from Upstate. The incorporation of 32P into MEK1 (K97R) by BRAF (V599E) is measured with final assay buffer conditions of 50 mM Tris pH 7.5, 10 mM MgCl2, 1 mM DTT, 100 mM sucrose, 100 μM sodium orthovanadate, 5 μM ATP and 2 μCi [γ 32P] ATP and 500 mg MEK1 Kinase dead substrate. The enzymatic reaction is stopped after 120 minutes with 8N HCl (hydrochloric acid) and 1 mM ATP. The solution is spotted on P81 filter paper and washed 4 times with 0.75% orthophosphoric acid and lastly with acetone. The dried P81 filter papers are read in a Micro-beta Trilux scintillation counter. The final concentration of DMSO is 1% in the assay. Compounds are screened at 10 μM concentration with pre-incubation of the enzymes in the presence of test compound for 45 minutes. Compounds of the invention were found to be inactive in this assy, e.g. ex. 33 (13% inhibition at 10 uM), ex. 1A (0% inhibition at 10 uM).
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 538, ALogP 5.68, HBA 8, HBD 0, PSA 99.86, QED 0.29
Compound (SMILES): Cc1ccc2c(-c3ccccc3F)cc(C(N)=O)nc2c1
InChIKey: IMNUYQQIVISJGO-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Biological Assay: The utility of the compounds in accordance with the present invention as antagonists of metabotropic glutamate receptor activity, in particular mGluR2 activity, may be demonstrated by methodology known in the art. Antagonist constants are determined as follows. The compounds of the present invention were tested in a fluorescence laser imaging plate reader based assay. This assay is a common functional assay to monitor Ca2+ mobilization in whole cells expressing recombinant receptor coupled with a promiscuous G-protein. CHO dhfr- cells stably expressing recombinant human mGluR2 and Gα16 loaded with Fluo-4 AM (Invitrogen, Carlsbad Calif.) are treated with various concentrations of antagonists of compounds and the Ca2+ response is monitored on a FLIPR384 (Molecular Devices, Sunnydale Calif.) for agonist activity.
Measurement: IC50 = 393 nM (pChEMBL 6.409999847412109)
Descriptors: MW 280.3, ALogP 3.45, HBA 2, HBD 1, PSA 55.98, QED 0.78
Compound (SMILES): O=C(c1ccc2cc(Oc3ccc(C(F)(F)F)cn3)ccc2n1)N1C[C@@H]2CN[C@@H]2C1
InChIKey: BFGDKCTUHKHGHR-SCLBCKFNSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FRET-Based Membrane Potential Assay: Two days prior to the experiment, frozen HEK293 cells stably expressing recombinant human Nav1.7 were quickly thawed and plated at 25,000 cells/well in growth medium [DMEM (Invitrogen #11965) with 10% HI FBS (Invitrogen #10082), 2 mM glutamine, 100 units/mL penicillin, 0.1 mg/mL streptomycin (PSG, Sigma #G1146), and 500 ug/mL Geneticin (Invitrogen #10131)] in black-walled, clear-bottom 384-well poly-D-lysine-coated assay plates (Greiner Bio-One, Frickenhausen, Germany) and incubated in a humidified 5% CO2 incubator at 37° C. On the day of the assay, medium was removed by aspiration, and cells were washed with assay buffer [HBSS (Invitrogen, Carlsbad, Calif.) containing 20 mM HEPES (Invitrogen, Carlsbad, Calif.)]. After washing, 30 uL assay buffer containing the fluorescent voltage-sensor probe CC2-DMPE (Invitrogen, Carlsbad, Calif.) at 20 uM and 0.01% pluronic F-127 (Invitrogen, Carlsbad, Calif.) was added to the cells. Cells were incubated for 40 minutes at room temperature in the dark. Following the incubation, the cells were washed and 30 uL assay buffer containing 2.5 uM DiSBAC2(3) substrate (Invitrogen, Carlsbad, Calif.) and 0.5 mM VABSC-1 (Invitrogen, Carlsbad, Calif.) was added to the cells. The cells were incubated for 90 minutes at room temperature in the dark. Fluorescence readings were made using a FLIPR TETRA (Molecular Devices, Sunnyvale Calif.) equipped with voltage-sensor probe optics. At the start of each experiment the optimal (EC80) concentration of depolarizing agent (veratridine) was determined by testing a dilution curve of assay buffer containing veratridine (Sigma-Aldrich, St. Louis, Mo.) and 1 mg/mL scorpion venom (SVqq, from Leiurus quinquestriatus; Sigma-Aldrich, St. Louis, Mo.). Compounds were dissolved in dimethyl sulfoxide, and 8-point, 1:3 dilution concentration-response curves were prepared in duplicate in dimethyl sulfoxide, followed by preparation of 0.8 uL/well daughter plates of the dilutions. Test compounds in the daughter plate were diluted to (Ë¿3x) solutions in assay buffer immediately before assaying. Using the FLIPR TETRA, 20 uL of the (3x) compound solutions were first added to the cells, then 20 uL of depolarizing solution (3xEC80 veratridine+SVqq) were added 3 minutes later to activate the channel. Changes in fluorescence were measured at wavelengths of 440-480 nm and 565-625 nm over the course of the experimental run. Membrane depolarization was expressed as a ratio of the maximum F440-480 nm/F565-625 nm reading above average baseline F440-480 nm/F565-625 nm reading. IC50 values were calculated from curve fits of the ratio data using a four-parameter logistic Hill equation (Accelrys Assay Explorer 3.3 Client, Accelrys, San Diego, Calif.) with percent inhibition plotted against compound concentration.
Measurement: IC50 = 3720 nM (pChEMBL 5.429999828338623)
Descriptors: MW 414.39, ALogP 3.48, HBA 5, HBD 1, PSA 67.35, QED 0.71
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N(C)CC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O)[C@@H](C)O)C(C)C)C(C)C
InChIKey: IIRHCNGNULZFKD-RESZXLJASA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 2357.8
Compound (SMILES): Cc1cccc(-c2ocnc2C(=O)Nc2cnn(CCc3cccc(F)c3)c2)c1
InChIKey: GYJRWJFMOASPQT-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: In Vitro 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 10 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 = 1780 nM (pChEMBL 5.75)
Descriptors: MW 390.42, ALogP 4.48, HBA 5, HBD 1, PSA 72.95, QED 0.53
Compound (SMILES): COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NS(=O)(=O)C2CC2)c1
InChIKey: DJEKOYRJPGXCQB-QLXKLKPCSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at glucocorticoid receptor in human ChaGoK1 cells assessed as inhibition of AP1-mediated transcriptional activity by measuring reduction in PMA-stimulated TRE-LacZ activity after 24 hrs in presence of MUG by fluorometric assay
Measurement: IC50 = 0.62 nM (pChEMBL 9.210000038146973)
Descriptors: MW 495.58, ALogP 4.76, HBA 6, HBD 1, PSA 82.45, QED 0.36
Compound (SMILES): Cc1ccc(F)c(-c2cccc(OCC(O)CN3CCc4ccccc4C3)c2)c1
InChIKey: LIHBGEGIJJSYEH-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 391.49, ALogP 4.6, HBA 3, HBD 1, PSA 32.7, QED 0.67
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)C4CCN(Cc5ccc(C(F)(F)F)cc5)CC4)cc3)nc(N(C)C)nc2c1
InChIKey: UEDRGVUEMGGOSD-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 = 706 nM (pChEMBL 6.150000095367432)
Descriptors: MW 576.67, ALogP 6.49, HBA 6, HBD 2, PSA 73.39, QED 0.25
Compound (SMILES): Cc1ccc2nc(N3CCCC3)nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c2c1
InChIKey: ZYZRJLLDBKNIGC-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 > 21952 nM (pChEMBL 4.658999919891357)
Descriptors: MW 455.54, ALogP 5.54, HBA 5, HBD 2, PSA 70.15, QED 0.4
Compound (SMILES): O=C1CC(c2ccccc2)CCN1C[C@H](O)CN1CCc2ccccc2C1
InChIKey: JGLKMORHYGTOQD-LWMIZPGFSA-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 364.49, ALogP 2.81, HBA 3, HBD 1, PSA 43.78, QED 0.89
Compound (SMILES): CC(C)(O)COc1ncnc2[nH]cc(/C=C/C(N)=O)c12
InChIKey: LSSSBVSRWFCJKB-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 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 276.3, ALogP 0.61, HBA 5, HBD 3, PSA 114.12, QED 0.69
Compound (SMILES): CC1(C)Cc2cccc(-c3nc4c(N[C@@H]5C[C@@H](COS(N)(=O)=O)[C@@H](O)C5)ncnc4[nH]3)c2O1
InChIKey: SPHQBJDPFBNVGT-GUTXKFCHSA-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 474.54, ALogP 1.5, HBA 9, HBD 4, PSA 165.34, QED 0.41
Compound (SMILES): Cc1cccc2cc(Cn3nc(Cl)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: UAFSATSBMZSOOD-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 434.86, ALogP 3.86, HBA 7, HBD 1, PSA 91.62, QED 0.47
Compound (SMILES): CC(=O)c1c(C)c2cnc(NC3CC(O)CCN3c3cccnc3)nc2n(C2CCCC2)c1=O
InChIKey: YRMZFPLNRCXCSY-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 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 462.55, ALogP 3.21, HBA 9, HBD 2, PSA 113.24, QED 0.56
Compound (SMILES): Cl.N=C(N)c1ccc(COc2ccc3cc(CC(NS(=O)(=O)c4ccccc4)C(=O)O)ccc3c2)cc1
InChIKey: YWWWAPWGLPAXQW-UHFFFAOYSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Displacement of fibrinogen from human platelet GP2b/GP3a receptor after 2 hrs by ELISA
Measurement: IC50 = 1330 nM (pChEMBL 5.880000114440918)
Descriptors: MW 503.58, ALogP 3.68, HBA 5, HBD 4, PSA 142.57, QED 0.19
Compound (SMILES): COc1cc(F)cc(-c2nn(Cc3cc4cccc(C)c4c(=O)n3-c3ccccc3C)c3ncnc(N)c23)c1
InChIKey: FQLIKSAJKYJLGL-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 520.57, ALogP 5.19, HBA 8, HBD 1, PSA 100.85, QED 0.34
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3nccs3)c2c(=O)n1-c1ccccc1
InChIKey: LHUTWLRZEUBNQJ-SFHVURJKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human recombinant full length N-terminal GST-tagged PI3K p110delta/p85alpha coexpressed in baculovirus infected Sf9 insect cells using diC8PIP2 as substrate incubated for 15 mins followed by substrate addition measured after 2 hr by ADP-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 531.6, ALogP 3.96, HBA 9, HBD 2, PSA 120.2, QED 0.33
Compound (SMILES): O=C(COc1cccc2ccccc12)NCC(O)CN1CCc2ccccc2C1
InChIKey: UNBDNRTZHNCAJV-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 390.48, ALogP 2.75, HBA 4, HBD 2, PSA 61.8, QED 0.65
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Oc2cc(NC3CCCC3)ncn2)C[C@@H]1O
InChIKey: SDTGWJVQSONSRT-UHTWSYAYSA-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 6.300000190734863)
Descriptors: MW 372.45, ALogP 0.57, HBA 8, HBD 3, PSA 136.66, QED 0.63
Compound (SMILES): CC(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cc3)nc2n(C2CCCC2)c1=O.Cl
InChIKey: NEIIOKOYNKDHAM-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 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 432.53, ALogP 3.26, HBA 8, HBD 2, PSA 92.15, QED 0.6
Compound (SMILES): CNc1n[nH]c2ccc(C(=O)N3CCC[C@H]3c3ccc(Cl)cc3)cc12
InChIKey: CUQBBHUITNFLKO-KRWDZBQOSA-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 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 354.84, ALogP 4.24, HBA 3, HBD 2, PSA 61.02, QED 0.74
Compound (SMILES): OC(CNc1cc(-c2ccc3ncn(C4COC4)c3c2)ccn1)CN1CCc2ccccc2C1
InChIKey: OBPDWHCNFFHMQJ-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 455.56, ALogP 3.5, HBA 7, HBD 2, PSA 75.44, QED 0.44
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](NC(=O)c2ccncc2)[C@H](O)[C@@H]1O
InChIKey: IINUZRFVTDDCRA-DBIOUOCHSA-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 6.300000190734863)
Descriptors: MW 331.35, ALogP -1.86, HBA 7, HBD 4, PSA 151.84, QED 0.49
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(Cl)cc4)cc3)nc(N(C)C)nc2c1
InChIKey: AOCHSTRFBNLJOW-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 = 227 nM (pChEMBL 6.639999866485596)
Descriptors: MW 445.95, ALogP 5.52, HBA 5, HBD 2, PSA 70.15, QED 0.41
Compound (SMILES): C/C=C\c1ccc2c(NCc3ccc(NC(=O)C4CCN(Cc5ccccc5)CC4)cc3)nc(N(C)C)nc2c1
InChIKey: CSQCUQGTDYPDOZ-YWEYNIOJSA-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 = 305 nM (pChEMBL 6.519999980926514)
Descriptors: MW 534.71, ALogP 6.19, HBA 6, HBD 2, PSA 73.39, QED 0.27
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(C3(C(=O)O)CCOCC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: JTCVYIPNQDUOGW-JCOAXYOVSA-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 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 655.73, ALogP 5.87, HBA 8, HBD 4, PSA 156.11, QED 0.21
Compound (SMILES): CN(C)c1nc(NCc2ccc(NC(=O)c3ccc(F)cc3)cc2)c2ccc(-c3cccnc3Cl)cc2n1
InChIKey: KNYUKCDFZOGMCJ-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 = 541 nM (pChEMBL 6.269999980926514)
Descriptors: MW 527, ALogP 6.41, HBA 6, HBD 2, PSA 83.04, QED 0.24
Compound (SMILES): CCc1cc2cnc(Nc3ccc(N4CCC(O)CC4)cc3)nc2n(C2CCCC2)c1=O
InChIKey: BVHYNYAQKJXHNB-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 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 433.56, ALogP 4.17, HBA 7, HBD 2, PSA 83.28, QED 0.63
Compound (SMILES): CCCC/C=C/c1ccc2nc(N(C)C)nc(NCc3ccc(C(=O)Nc4ccc(F)cc4)cc3)c2c1
InChIKey: BHIOLGCZMCCQKQ-BQYQJAHWSA-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 = 537 nM (pChEMBL 6.269999980926514)
Descriptors: MW 497.62, ALogP 6.9, HBA 5, HBD 2, PSA 70.15, QED 0.23
Compound (SMILES): Cc1ccc2nc(N3CCCCCC3)nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c2c1
InChIKey: ZTWSDTGYWPVPFY-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 = 2011 nM (pChEMBL 5.699999809265137)
Descriptors: MW 483.59, ALogP 6.32, HBA 5, HBD 2, PSA 70.15, QED 0.34
Compound (SMILES): C=Cc1cccc(-c2ccc3nc(N(C)C)nc(NCc4ccc(C(=O)Nc5ccc(F)cc5)cc4)c3c2)c1
InChIKey: KEPNWCPTSUWOJV-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 = 308 nM (pChEMBL 6.510000228881836)
Descriptors: MW 517.61, ALogP 7.01, HBA 5, HBD 2, PSA 70.15, QED 0.23
Compound (SMILES): OC(COc1ccc(Cc2ccccc2)cc1)CN1CCc2ccccc2C1
InChIKey: AFAXWMGSIKCSQW-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 373.5, ALogP 4.08, HBA 3, HBD 1, PSA 32.7, QED 0.68
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3ncnc4[nH]nc(C(N)=O)c34)n(C3CC3)c(=O)c12
InChIKey: MGLYNEZGHJLIBT-NSHDSACASA-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 < 10000 nM (pChEMBL 5)
Descriptors: MW 403.45, ALogP 2.58, HBA 7, HBD 3, PSA 131.58, QED 0.47
Compound (SMILES): CN(CC(O)CN1CCc2ccccc2C1)c1cccc(CNC2CCOCC2)c1
InChIKey: CDGRGCNRTUXAGY-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 409.57, ALogP 2.81, HBA 5, HBD 2, PSA 47.97, QED 0.7
Compound (SMILES): CN1CC[C@H](c2c(O)cc(O)c3c(=O)cc(-c4ccc(F)cc4)oc23)[C@H](O)C1
InChIKey: GBTFAVMORZGOBX-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 = 129.1 nM (pChEMBL 6.889999866485596)
Descriptors: MW 385.39, ALogP 2.79, HBA 6, HBD 3, PSA 94.14, QED 0.63
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ccnc(C(=O)N[C@H]3CCc4ccccc43)c2)[C@H](O)[C@@H]1O
InChIKey: WNNGIOXQBKNFQU-GKQNRZDQSA-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 462.53, ALogP 0.24, HBA 8, HBD 5, PSA 163.87, QED 0.39
Compound (SMILES): CC(=O)Nc1nc2ccc(-c3nn(Cc4cc5cccc(C)c5c(=O)n4C4CC4)c4ncnc(N)c34)cc2s1
InChIKey: RHARTZQJZKQTSU-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 536.62, ALogP 4.65, HBA 10, HBD 2, PSA 133.61, QED 0.33
Compound (SMILES): OC(COc1cccc(-c2ccc3ncn(C4CCNCC4)c3c2)c1)CN1CCc2ccccc2C1
InChIKey: LEQYQKYGCHZQCI-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 4.43, HBA 6, HBD 2, PSA 62.55, QED 0.41
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Nc2c(Cl)cnc3[nH]c(-c4cccc5ccccc45)nc23)C[C@@H]1O
InChIKey: HOZBHDDPDLQLLO-IYOUNJFTSA-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 487.97, ALogP 3.2, HBA 7, HBD 4, PSA 143.22, QED 0.33
Compound (SMILES): O=C(Nc1ccc(CNc2nc(NC3CCC3)nc3ccccc23)cc1)c1ccc(F)cc1
InChIKey: BCIHVYADZVHSSY-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 = 991 nM (pChEMBL 6)
Descriptors: MW 441.51, ALogP 5.6, HBA 5, HBD 3, PSA 78.94, QED 0.35
Compound (SMILES): O=C(Nc1ccc(CNc2nc(NCc3ccco3)nc3ccc(C(F)(F)F)cc23)cc1)c1ccc(Cl)cc1
InChIKey: WQDGHNADASGKAA-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 = 1284 nM (pChEMBL 5.889999866485596)
Descriptors: MW 551.96, ALogP 7.37, HBA 6, HBD 3, PSA 92.08, QED 0.19
Compound (SMILES): CC(Oc1ccccc1)C(=O)NCC(O)CN1CCc2ccccc2C1
InChIKey: WBVVJINBZYMVKR-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 354.45, ALogP 1.99, HBA 4, HBD 2, PSA 61.8, QED 0.8
Compound (SMILES): Nc1ncnc2c1c(I)nn2Cc1cc2cccc(I)c2c(=O)n1C1CCCC1
InChIKey: SCFMCZSBBABLBK-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 612.21, ALogP 4.1, HBA 7, HBD 1, PSA 91.62, QED 0.35
Compound (SMILES): Cn1cnc2cc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)ccc21
InChIKey: NETFEXKPQFDURR-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 413.52, ALogP 4.04, HBA 5, HBD 1, PSA 50.52, QED 0.52
Compound (SMILES): O=C(COc1ccccc1)NCC(O)CN1CCc2ccccc2C1
InChIKey: HLELTZAGWIXRNB-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 340.42, ALogP 1.6, HBA 4, HBD 2, PSA 61.8, QED 0.8
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2cc(N[C@H]3CCc4ccccc43)ncn2)[C@H](O)[C@@H]1O
InChIKey: RUHJKRPGNBYWRN-OUYBGJKKSA-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 435.51, ALogP 0.32, HBA 9, HBD 5, PSA 159.69, QED 0.41
Compound (SMILES): CC1CN(CC(O)COc2cccc(-c3ccc4ncn(C)c4c3)c2)Cc2ccccc21
InChIKey: XKDDGKUZFMGZBV-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 4.6, HBA 5, HBD 1, PSA 50.52, QED 0.49
Compound (SMILES): Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3C#N)n(-c3ccccc3)c(=O)c12
InChIKey: JRRIJVZLPMMJSV-ZDUSSCGKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal His-tagged full length p110delta/recombinant human full length p85alpha using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 386.42, ALogP 2.21, HBA 9, HBD 2, PSA 126.92, QED 0.55
Compound (SMILES): O=C(COc1ccccc1OCCN1CCOCC1)NC[C@H](O)CN1CCc2ccccc2C1
InChIKey: BXNXEQIJKQNNBX-QHCPKHFHSA-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 469.58, ALogP 1.31, HBA 7, HBD 2, PSA 83.5, QED 0.51
Compound (SMILES): CC(C)S(=O)(=O)N1CCN(c2ccc(OC[C@@H]3CO[C@@](Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC1
InChIKey: MVZWJEJFJUUOER-SHQCIBLASA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of recombinant CYP11B1 (unknown origin) overexpressed in human AD293 cells assessed as reduction in cortisol formation preincubated for 60 mins followed by addition of 11-deoxycortisol as substrate measured after 12 hrs by LC-MS/MS analysis
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 595.55, ALogP 4.4, HBA 8, HBD 0, PSA 86.13, QED 0.36
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cc(N2CCOCC2)nc(N)n1
InChIKey: DEFBACDLTQLHSG-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Enzyme Assay: Final assay conditions were 4 pM cRaf, 3 uM ATP, 10 nM biotin tagged MEK1 kinase dead protein substrate. Reactions were performed in Greiner384 well plates, catalog #784075. Reaction buffer was 50 mM Tris, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 0.01% Tween-20, 0.05% BSA and 1 mM DTT. 5 ul of 2×cRaf plus MEK1 were dispensed into plates containing 0.25 ul of compound in 100% DMSO and incubated at room temperature for 30 minutes. Reactions were started by addition of 5 ul of 2×ATP. Reactions were run for two hours and terminated by addition of 10 ul of 2× antibody and Alphascreen bead mixture in Stop Buffer. Stop Buffer was 50 mM Tris, pH 7.5, 0.005% Tween-20, 25 mM EDTA.
Measurement: IC50 = 0.344 nM (pChEMBL 9.460000038146973)
Descriptors: MW 457.46, ALogP 4.14, HBA 6, HBD 2, PSA 93.37, QED 0.61
Compound (SMILES): Nc1onc(-c2c(Cl)cccc2Cl)c1C(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: VGNWINMWRQYNCC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 assessed as reduction in CO2 hydration preincubated for 15 mins by stopped flow assay
Measurement: Ki = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 427.27, ALogP 3.13, HBA 6, HBD 3, PSA 141.31, QED 0.58
Compound (SMILES): COc1cc(C(=O)NCc2ccc(Cl)cc2SCC(C)C)ccc1-c1cn[nH]c1
InChIKey: QUZWXWZCRHSTEK-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
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 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 429.97, ALogP 5.42, HBA 4, HBD 2, PSA 67.01, QED 0.47
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(Cl)c(OC2C3CC4CC2CC(Cl)(C4)C3)cc1F
InChIKey: QNKJCLDQVPZBAW-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay: Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel alpha -subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37 C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating.
Measurement: IC50 = 42.3 nM (pChEMBL 7.369999885559082)
Descriptors: MW 436.33, ALogP 3.73, HBA 4, HBD 1, PSA 72.47, QED 0.73
Compound (SMILES): COc1ccc(C(=O)C2CCN(C3CCN(Cc4nccc(=O)[nH]4)C3=O)CC2)cc1
InChIKey: ZGPMZIHTBVGHFX-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Biochemical Assay: The autoparsylation activity of the TNKS 1/2 or PARP1/2 enzymes was measured by the liquid chromatography-mass spectrometry (LC/MS) detection of nicotinamide as readout. Compound activity in inhibiting the TNKS and PARP autoparsylation was evaluated by IC50 measurements. In the compound screening assays, the reaction is composed of 5 uL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 uM, 20 nM of purified enzyme, and 250 uM of p-NAD+ in the 1x Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 uL of 5x quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 uL of the 5x quenching solution per well was added prior to the addition of p-NAD+. The % Inhibition was calculated as: (Control-Sample)/(Control-Background)*100. "Control" is the average value of 8 wells without compound; and "Background" is the average of 8 wells mixed with 5x quenching solution measured prior to initiation of the reaction.
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 410.47, ALogP 1.47, HBA 6, HBD 1, PSA 95.6, QED 0.72
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cc(N2CC3(COC3)C2)nc(N2CCOCC2)n1
InChIKey: JSNUOUDTFPPBCQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: In Vitro Enzyme Assay: Final assay conditions were 4 pM cRaf, 3 uM ATP, 10 nM biotin tagged MEK1 kinase dead protein substrate. Reactions were performed in Greiner384 well plates, catalog #784075. Reaction buffer was 50 mM Tris, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 0.01% Tween-20, 0.05% BSA and 1 mM DTT. 5 ul of 2×cRaf plus MEK1 were dispensed into plates containing 0.25 ul of compound in 100% DMSO and incubated at room temperature for 30 minutes. Reactions were started by addition of 5 ul of 2×ATP. Reactions were run for two hours and terminated by addition of 10 ul of 2× antibody and Alphascreen bead mixture in Stop Buffer. Stop Buffer was 50 mM Tris, pH 7.5, 0.005% Tween-20, 25 mM EDTA.
Measurement: IC50 = 2.454 nM (pChEMBL 8.609999656677246)
Descriptors: MW 539.56, ALogP 4.4, HBA 7, HBD 1, PSA 79.82, QED 0.52
Compound (SMILES): CN(C)CCc1cn(-c2ccc(Oc3ccccc3)cc2)c2ccc(C[C@H]3COC(=O)N3)cc12
InChIKey: JWJIQDRIDZBPSB-QFIPXVFZSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiology Assay: For electrophysiological recordings the external solution was either standard, DMEM supplemented with 10 mM HEPES (pH adjusted to 7.34 with NaOH and the osmolarity adjusted to 320) or Tyrodes salt solution (Sigma, USA) supplemented with 10 mM HEPES (pH adjusted to 7.4 with NaOH; osmolarity=320). The internal pipette solution contained (in mM): NaCl (10), CsF (140), CaCl2 (1), MgCl2 (5), EGTA (11), HEPES (10: pH 7.4, 305 mOsm). Compounds were prepared first as series of stock solutions in DMSO and then dissolved in external solution; DMSO content in final dilutions did not exceed 0.3%. At this concentration, DMSO did not affect sodium currents. Vehicle solution used to establish base line was also contacting 0.3% DMSO.
Measurement: Ki = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 455.56, ALogP 5.18, HBA 5, HBD 1, PSA 55.73, QED 0.4
Compound (SMILES): C=CC(=O)NCCn1nc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc21
InChIKey: ZAZQUFKQXMNBTJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 400.44, ALogP 3.17, HBA 7, HBD 2, PSA 107.95, QED 0.46