lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)S(=O)(=O)n1cc(C(=O)NC2CC3COCC(C2)N3C)c2ccccc21
InChIKey: WQOYQHFFLJQYOW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: In Vitro Inhibition of Ca Flux Assay: The 5HT3 antagonist activity of the compounds of the invention was determined by measuring the ability of the compounds to inhibit the calcium flux activity of 3HT3a receptor expressed in HEK-293T cells. HEK-293T cells were transfected with the 5HT3a expression construct using Xtreme Gene 9 (Roche) in 150 mm tissue culture treated plates and incubated for 24 hours at 37 °C. Cells were then split and plated at a density of 60K cells/well in poly-lysine coated, black 96-well plates with clear bottoms (BD BioSciences) and incubated overnight at 37 °C. Growth media was removed and cells loaded with 200 uL calcium indicator dye in HBSS containing 20 mM HEPES (Calcium 5 Assay kit, Molecular Devices) and incubated at 37 °C. for 1 hour. While cells were incubating, the 10× antagonist and agonist/antagonist addition plates were made. For 10× antagonist plate: half log serial dilutions (final concentrations range from 10−7 through 10−10 with the bottom well a negative, no ligand control) were made from test compounds in DMSO at a 1000× concentration and then diluted to 10× in HBSS/20 mM HEPES. For addition plate: 5HT was diluted to 100× in HBSS/20 mM HEPES (final concentration in the assay−216 nM) and 15 uL was added to each well of the addition plate, 15 uL of 10× compound was also added to the addition plate, and finally 120 uL of HBSS/20 mM HEPES (for a total of 150 uL). Cells were then removed from the incubator and equilibrated to room temperature for 10 minutes, then 22.5 uL of 10× test compounds were added in triplicate to the plates and incubated at room temperature for 10 minutes (Tropisetron was used as a positive control in every assay). Test plate and addition plate were loaded into the FlexStation III (Molecular Devices), and using the fluidics, 22.5 uL compound additions were made (at t=~17 seconds), and fluorescence was measured for 90 seconds, reading every 2.2 seconds.
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 405.52, ALogP 1.82, HBA 6, HBD 1, PSA 80.64, QED 0.84
Compound (SMILES): Cn1nccc1CN1CCC(CC#N)(n2cc(C(N)=O)c(Nc3ccnc(F)c3)n2)CC1
InChIKey: RVISMZBNCUSIJE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF 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 uL of 1.11x enzyme and 1.11x substrate in 1x 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 room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x 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.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 437.48, ALogP 1.9, HBA 9, HBD 2, PSA 130.68, QED 0.54
Compound (SMILES): Cc1cc(Nc2cc(C(F)(F)F)ccn2)nc(-c2ccc(NC3CCN(C(=O)c4ccc(-c5ccccc5)cc4)CC3)nc2)c1
InChIKey: SOSIEIRSEQHQPA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Homogeneous Time-Resolved Fluorescence (HTRF) Assay: A recombinant GST-hSyk fusion protein was used to measure potency of compounds to inhibit human Syk activity. The recombinant human GST-Syk (Carna Biosciences #08-176) (5 pM final concentration) was incubated with various concentrations of the inhibitor diluted in DMSO (0.1% final concentration) for 10 minutes at room temperature in 15 mM Tris-HCl (pH 7.5), 0.01% tween 20, 2 mM DTT in 384 well plate format. To initiate the reaction the biotinylated substrate peptide (250 nM final concentration) that contains the phosphorylation site for Syk was added with magnesium (5 mM final concentration) and ATP (25 uM final concentration). Final volume of the reaction was 10 uL. Phosphorylation of the peptide was allowed to proceed for 45x at room temperature. To quench the reaction and detect the phosphorylated product, 2 nM of a Europium-anti-phosphotyrosine antibody (Perkin Elmer #AD0161) and 70 nM SA-APC (Perkin-Elmer #CR130-100) were added together in 15 mM Tris pH 7.5.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 608.67, ALogP 7.99, HBA 6, HBD 2, PSA 83.04, QED 0.19
Compound (SMILES): CCCCOc1ccc(-c2nc(-c3ccc4c(c3)CCN4CC(N)(CO)CO)no2)cc1Cl
InChIKey: GLNFOJKGKLUMRG-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: [35S]-GTPgamaS Binding Assay: Selected Compounds of the Examples were evaluated at Millipore Corporation, USA, using S1P1 receptor; [35S]-GTPgamaS binding assay. A [35S]-GTPgamaS binding assay at Millipore was conducted by GPCR Profiler Custom Service Laboratory, Temecula, Calif., Millipore, Inc. to monitor dose-dependent agonist selectivity for selected Examples against the S1P1 receptors. The assay was completed with sample compounds subjected to an eight-point, four-fold dose response curve with starting concentration of 10 uM. Selectivity was determined upon initial addition of compounds followed by a 30 minute incubation at 30° C. Following compound incubation, bounded [35S]-GTPgamaS was determined by filtration and scintillation counting. Independently, selected compounds were evaluated for S1P1 and S1P3 agonistic activity. The S1P1 assay system was GTPgama-S35 binding in membranes from CHO K1 cells, expressing S1P1 human receptor. The S1P3 assay system was calcium mobilization in CHO K1 cells expression.
Measurement: EC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 472.97, ALogP 3.28, HBA 8, HBD 3, PSA 117.87, QED 0.38
Compound (SMILES): c1ccc2nc(OCc3cn4c(-c5ccc(N6CCNCC6)nc5)cnc(-c5ccc6[nH]cnc6c5)c4n3)ccc2c1
InChIKey: KVNLMOQRADGOTB-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: In Vitro Assay rPDE10: Rat recombinant PDE10a (rPDE10a) was expressed in Sf9 cells using a recombinant rPDE10a baculovirus construct. Cells were harvested after 48 h of infection and the rPDE10a protein was purified by metal chelate chromatography on Ni-sepharose 6FF. Tested compounds were dissolved and diluted in 100% DMSO to a concentration 100 fold of the final concentration in the assay. Compound dilutions (0.4 uL) were added in 384 well plates to 20 uL of incubation buffer (50 mM Tris pH 7.8, 8.3 mM MgCl2, 1.7 mM EGTA). 10 uL of rPDE10a enzyme in incubation buffer was added and the reaction was started by addition of 10 uL substrate to a final concentration of 60 nM cAMP and 0.008 uCi 3H-cAMP. The reaction was incubated for 60 min at rt. After incubation, the reaction was stopped with 20 uL of 17.8 mg/mL PDE SPA beads. After sedimentation of the beads during 30 min the radioactivity was measured in a Perkin Elmer Topcount scintillation counter and results were expressed as cpm. For blank values the enz
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 553.63, ALogP 4.87, HBA 9, HBD 2, PSA 109.15, QED 0.3
Compound (SMILES): COc1cc(C)cc2cc(-c3c(COCCO)c(CN4CCNC(=O)C4)n4ncnc(N)c34)sc12
InChIKey: KIKNWMSSCYMPJH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: High ATP Kinase Assay: For the assay, 50 nl of each stock solution of the test compound in DMSO was pipetted into a black, low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany) 2 Î¼l of a solution of the above FGFR-1 fusion protein in aqueous assay buffer [8 mM MOPS pH 7.0, 10 mM magnesium acetate, 1.0 mM dithiothreitol, 0.05% (w/v) bovine serum albumin (BSA), 0.07% (v/v) Tween-20, 0.2 mM EDTA] was added, and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compound to the enzyme. Then, the kinase reaction was started by the addition of 3 ul of a solution of adenosine triphosphate (ATP, 3.3 mM; final concentration in the 5 ul assay volume=2 mM) and substrate (0.16 uM; final concentration in the 5 ul assay volume=0.1 uM) in assay buffer, and the resulting mixture was incubated for a reaction time of 15 min at 22° C. The concentration of FGFR-1 fusion protein was adjusted depending on the activity of the enzyme lot.
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 496.59, ALogP 1.95, HBA 10, HBD 3, PSA 127.24, QED 0.32
Compound (SMILES): CC(C)OC(=O)[C@H](C)NP(=O)(OC[C@H]1O[C@@H](c2cnc3c(N)ncnn23)[C@](C)(N)[C@@H]1O)Oc1ccccc1
InChIKey: CDSQMEYITYMMTN-GHRVZJKLSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Cell-Based HCV Replicon Assay: To measure cell-based anti-HCV activity of selected compounds of the present invention, replicon cells were seeded at 5000 cells/well in 96-well collagen I-coated Nunc plates in the presence of the test compound. Various concentrations of test compound, typically in 10 serial 2-fold dilutions, were added to the assay mixture, with the starting concentration ranging from 250 uM to 1 uM. The final concentration of dimethylsulfoxide was 0.5% fetal bovine serum was 5%, in the assay media. Cells were harvested on day 3 by the addition of 1x cell lysis buffer (Ambion cat #8721).The replicon RNA level was measured using real time PCR (Taqman assay). The amplicon was located in 5B. The PCR primers were: 5B.2F, ATGGACAGGCGCCCTGA (SEQ ID. NO. 1); 5B.2R, TTGATGGGCAGCTTGGTTTC (SEQ ID. NO. 2); the probe sequence was FAM-labeled CACGCCATGCGCTGCGG (SEQ ID. NO. 3). GAPDH RNA was used as endogenous control and was amplified in the same reaction as NS5B (multiplex PCR) using primers and VIC-labeled probe recommended by the manufacturer (PE Applied Biosystem). The real-time RT-PCR reactions were run on ABI PRISM 7900HT Sequence Detection System using the following program: 48° C. for 30 minutes, 95° C. for 10 minutes, 40 cycles of 95° C. for 15 sec, 60° C. for 1 minute. The ΔCT values (CT5B-CTGAPDH) were plotted against the concentration of test compound and fitted to the sigmoid dose-response model using XLfit4 (MDL). EC50 was defined as the concentration of inhibitor necessary to achieve ΔCT=1 over the projected baseline; EC90 the concentration necessary to achieve ΔCT=3.2 over the baseline. Alternatively, to quantitate the absolute amount of replicon RNA, a standard curve was established by including serially diluted T7 transcripts of replicon RNA in the Taqman assay. All Taqman reagents were from petroleum ether Applied Biosystems. Such an assay procedure was described in detail in e.g. Malcolm et al., Antimicrobial Agents and Chemotherapy 50: 1013-1020 (2006).
Measurement: EC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 549.53, ALogP 1.36, HBA 13, HBD 4, PSA 198.44, QED 0.21
Compound (SMILES): COc1cc(O)ccc1-c1ccc2c(-c3nc4c(SCCO)cccc4[nH]3)n[nH]c2c1
InChIKey: TUHRSPDOKFFKGG-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human CDK2 expressed in baculovirus infected Sf9 insect cells/full length recombinant truncated cyclin A expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by [32P]ATP based scintillation counting analysis
Measurement: Ki = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 432.51, ALogP 4.57, HBA 6, HBD 4, PSA 107.05, QED 0.29
Compound (SMILES): Cn1c(-c2ccccc2)nc2c(N[C@@H]3C[C@@H](COS(N)(=O)=O)[C@@H](O)C3)ncnc21
InChIKey: SNLWVTPZHUQJPU-MJBXVCDLSA-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 418.48, ALogP 0.8, HBA 9, HBD 3, PSA 145.25, QED 0.53
Compound (SMILES): CN1CCC[C@H]1COc1cc(C#CCCCCO)cc([N+](=O)[O-])c1
InChIKey: CKMGCGVDSOWJQZ-INIZCTEOSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30926
Assay: Displacement of [3H]-epibatine from human alpha3beta4-nACHR expressed in HEK243 cell membranes preincubated for 5 mins followed by overnight incubation with [3H]-epibatine by liquid scintillation counting analysis
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 332.4, ALogP 2.58, HBA 5, HBD 1, PSA 75.84, QED 0.36
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCc3ccccc3)n2)c1
InChIKey: LWOIOAVZAUIQIB-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of human recombinant full length His-tagged CDK9/cyclin T1 expressed in insect cells using biotin-Ttds-YISPLKSPYKISEG as substrate preincubated for 15 mins measured after 25 mins by TR-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 464.52, ALogP 4.54, HBA 7, HBD 1, PSA 94.07, QED 0.41
Compound (SMILES): Cc1ccccc1OCC(=O)NCC(O)CN1CCc2ccccc2C1
InChIKey: GLSQQXKKZSYOIS-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 354.45, ALogP 1.91, HBA 4, HBD 2, PSA 61.8, QED 0.8
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Nc2ncnc3nc(-c4ccc(OCc5ccccc5)cc4)[nH]c23)C[C@@H]1O
InChIKey: GKCIONAECOZFSW-NSHGMRRFSA-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 510.58, ALogP 2.37, HBA 9, HBD 4, PSA 165.34, QED 0.26
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3cncs3)c2c(=O)n1-c1ccccc1
InChIKey: VLBCDBMQYLNSLY-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 > 8000 nM (pChEMBL 5.0970001220703125)
Descriptors: MW 531.6, ALogP 3.96, HBA 9, HBD 2, PSA 120.2, QED 0.33
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)nc(NCCCN3CCN(C)CC3)nc2c1
InChIKey: LLPKAIARVBKPCU-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 = 2322 nM (pChEMBL 5.630000114440918)
Descriptors: MW 541.68, ALogP 4.99, HBA 7, HBD 3, PSA 85.42, QED 0.24
Compound (SMILES): CNC(=O)c1cccc(N[C@@H](C(=O)N2CCC[C@@H]2c2cc(NC(=O)OC)ccc2S(=O)(=O)C(C)C)c2ccc(OC)c(OC)c2)c1
InChIKey: FVBPDJDCDXVVLW-PDDLMNHVSA-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
Measurement: Ki > 13000 nM (pChEMBL 4.886000156402588)
Descriptors: MW 652.77, ALogP 4.94, HBA 9, HBD 3, PSA 152.37, QED 0.26
Compound (SMILES): C[C@H](Oc1cccc2cccnc12)C(=O)NC[C@H](O)CN1CCc2ccccc2C1
InChIKey: YPSQMJYWDJFOKN-UWJYYQICSA-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 405.5, ALogP 2.54, HBA 5, HBD 2, PSA 74.69, QED 0.63
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)COCc3ccccc3)cc2)c2ccccc2n1
InChIKey: ZQUXKUOHGYUDEN-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 > 2924 nM (pChEMBL 5.533999919891357)
Descriptors: MW 427.51, ALogP 4.44, HBA 6, HBD 3, PSA 88.17, QED 0.37
Compound (SMILES): O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(OCCO)cc3)cc12
InChIKey: YGKWXCWHOYVSAU-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54619
Assay: Allosteric activation of human AMPK alpha1/beta1/gamma1 by TR-FRET assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 331.76, ALogP 3.56, HBA 3, HBD 3, PSA 82.55, QED 0.67
Compound (SMILES): O=C(COc1cccc2[nH]c(=O)cnc12)NCC(O)CN1CCc2ccccc2C1
InChIKey: BHHSWQSNBXDCGH-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 408.46, ALogP 0.84, HBA 6, HBD 3, PSA 107.55, QED 0.53
Compound (SMILES): O=C(NC[C@@H](O)CN1CCc2ccccc2C1)Oc1ccccc1
InChIKey: ISPNKABZQKKZLU-QGZVFWFLSA-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 326.4, ALogP 2.19, HBA 4, HBD 2, PSA 61.8, QED 0.88
Compound (SMILES): O=C(Nc1cccnc1)c1cccc(OCC(O)CN2CCc3ccccc3C2)c1
InChIKey: SBOSTJQAZQCCSN-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 403.48, ALogP 3.13, HBA 5, HBD 2, PSA 74.69, QED 0.63
Compound (SMILES): Cc1ccc2nc(N3CCC3)nc(NCc3ccc(NC(=O)C4CCN(Cc5ccccc5)CC4)cc3)c2c1
InChIKey: RNIJMIWIFOAASJ-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 = 423 nM (pChEMBL 6.369999885559082)
Descriptors: MW 520.68, ALogP 5.61, HBA 6, HBD 2, PSA 73.39, QED 0.31
Compound (SMILES): CC1CN(CC(O)COc2cccc(CNC3CCCC3)c2)Cc2ccccc21
InChIKey: NLFFHISKVLNNGK-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 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 394.56, ALogP 4.08, HBA 4, HBD 2, PSA 44.73, QED 0.71
Compound (SMILES): O=c1[nH]c2ccc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)cc2[nH]1
InChIKey: YZYBGQZLQHWYCP-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 415.49, ALogP 3.32, HBA 4, HBD 3, PSA 81.35, QED 0.45
Compound (SMILES): CS(=O)(=O)Nc1ccccc1C(=O)NCC(O)CN1CCc2ccccc2C1
InChIKey: ITKVBCUHRRICIL-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 403.5, ALogP 1.21, HBA 5, HBD 3, PSA 98.74, QED 0.65
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Nc2ncnc3[nH]c(-c4cccc(-c5ccccc5)c4)nc23)C[C@@H]1O
InChIKey: WCQSTRUHXLBIAX-OTWHNJEPSA-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 480.55, ALogP 2.46, HBA 8, HBD 4, PSA 156.11, QED 0.31
Compound (SMILES): O=C(COc1cccc(F)c1)NCC(O)CN1CCc2ccccc2C1
InChIKey: DYLGANMZPUAKDT-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 358.41, ALogP 1.74, HBA 4, HBD 2, PSA 61.8, QED 0.79
Compound (SMILES): CN(C)CCOc1ccc(Nc2cc(-n3ccnc3)ncn2)nc1
InChIKey: PKZBARFMXVRZEC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of recombinant full-length human C-terminal His6-tagged CDK2/recombinant full-length human N-terminal GST-tagged cyclin E using fluorescein-QSPKKG-CONH2 as substrate after 60 mins by off-chip mobility shift assay
Measurement: IC50 = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 325.38, ALogP 1.74, HBA 8, HBD 1, PSA 80.99, QED 0.71
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cc(O)cc(F)c4)c4c(N)ncnc43)n(-c3ccccc3O)c(=O)c12
InChIKey: XOZCRBUNRWGVCR-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 < 10000 nM (pChEMBL 5)
Descriptors: MW 508.51, ALogP 4.29, HBA 9, HBD 3, PSA 132.08, QED 0.32
Compound (SMILES): Cc1cccc2cc(C(C)Nc3ncnc4[nH]cnc34)n(C3CCC3)c(=O)c12
InChIKey: OVBKKAQIDXMNIF-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 374.45, ALogP 3.87, HBA 6, HBD 2, PSA 88.49, QED 0.57
Compound (SMILES): COC(=O)/C=C/c1c[nH]c2ncnc(OCC(C)C)c12
InChIKey: YSMQCLKSRAHMMV-SNAWJCMRSA-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 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 275.31, ALogP 2.18, HBA 5, HBD 1, PSA 77.1, QED 0.67
Compound (SMILES): Cl.O=C(O)C(Cc1ccc2cc(OCCCC3CCNCC3)ccc2c1)NS(=O)(=O)c1ccc(Br)cc1
InChIKey: GTQXJPRTKXXZIE-UHFFFAOYSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Antagonist activity at GP2b/GP3a receptor in human platelet rich plasma assessed as inhibition of ADP-induced platelet aggregation preincubated for 1 min followed by ADP addition by aggregometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 575.52, ALogP 4.74, HBA 5, HBD 3, PSA 104.73, QED 0.29
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3ncnc4[nH]ccc34)n(-c3ccccc3)c(=O)c12
InChIKey: RYFJDPSDHUCQPR-INIZCTEOSA-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 395.47, ALogP 4.74, HBA 5, HBD 2, PSA 75.6, QED 0.46
Compound (SMILES): CCN(CC)c1nc(NCc2ccc(NC(=O)c3ccc(F)cc3)cc2)c2ccccc2n1
InChIKey: XTAJUPMOXJABGL-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 = 1264 nM (pChEMBL 5.900000095367432)
Descriptors: MW 443.53, ALogP 5.48, HBA 5, HBD 2, PSA 70.15, QED 0.38
Compound (SMILES): CC(C)(C)c1cnc(CSc2cnc(NC(=O)CCCC(=O)NO)s2)o1
InChIKey: CNNOAGXHCAVQKZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of C-terminal His6-tagged full length CDK2/N-terminal GST-tagged recombinant full length human cyclin E1 expressed in baculovirus infected SF21 insect cells using histone H1 as substrate after 2 hrs in presence of [gamma-33P]-ATP
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 398.51, ALogP 3.34, HBA 8, HBD 3, PSA 117.35, QED 0.35
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccc(O)cc3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: LDYHWJYPYDCMNK-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 488.55, ALogP 4.75, HBA 8, HBD 2, PSA 111.85, QED 0.37
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4F)ccc3o2)cc1)c1ccccc1F
InChIKey: IZGYHBGXECNFGB-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 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 541.56, ALogP 5.37, HBA 6, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): CC(=O)c1cccc(-c2cccc(OCC(O)CN3CCc4ccccc4C3)c2)c1
InChIKey: ODJBWOYBRMTPAI-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 401.51, ALogP 4.35, HBA 4, HBD 1, PSA 49.77, QED 0.6
Compound (SMILES): Cn1cc2ccc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)nc2n1
InChIKey: VFVDOVAAMDWKIO-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 414.51, ALogP 3.43, HBA 6, HBD 1, PSA 63.41, QED 0.52
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Oc2cc(N[C@H]3CCCc4ccccc43)ncn2)C[C@@H]1O
InChIKey: DNGNWDJRZARZSC-MVJTYMMSSA-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 434.52, ALogP 1.7, HBA 8, HBD 3, PSA 136.66, QED 0.6
Compound (SMILES): OC(CCc1cccc(CNC2CCCC2)c1)CN1CCc2ccccc2C1
InChIKey: RIRAPLTXMZUEMQ-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 = 10001 nM (pChEMBL 5)
Descriptors: MW 378.56, ALogP 4.07, HBA 3, HBD 2, PSA 35.5, QED 0.73
Compound (SMILES): Cl.O=C(O)[C@]1(Cc2cccc(Nc3nccs3)n2)CC[C@@H](Oc2cccc(C(F)(F)F)c2F)CC1
InChIKey: CDUNWQDJXVYZLJ-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 = 32 nM (pChEMBL 7.5)
Descriptors: MW 495.5, ALogP 6.07, HBA 6, HBD 2, PSA 84.34, QED 0.39
Compound (SMILES): CC(C)n1c(Cn2nc(-c3cc(O)cc(F)c3)c3c(N)ncnc32)cc2ccccc2c1=O
InChIKey: XURXVIGPYCYFFN-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 444.47, ALogP 3.86, HBA 8, HBD 2, PSA 111.85, QED 0.44
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3ncnc4[nH]cc(Br)c34)n(C3CC3)c(=O)c12
InChIKey: RHAFIPJCZAUEQH-LBPRGKRZSA-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 < 1000 nM (pChEMBL 6)
Descriptors: MW 438.33, ALogP 4.85, HBA 5, HBD 2, PSA 75.6, QED 0.48
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3ccc(F)c(F)c3)cc2)c2c(C)cccc2n1
InChIKey: PSTPMXJKYVTPGU-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 = 1145 nM (pChEMBL 5.940000057220459)
Descriptors: MW 433.46, ALogP 5.12, HBA 5, HBD 3, PSA 78.94, QED 0.39
Compound (SMILES): CN1Cc2cc(ccc2S(=O)(=O)C2CC2)NC(=O)N(CC2CC2)CCc2cccc(c2)C(Nc2ccc3c(N)ncc(F)c3c2)C1=O
InChIKey: AXIFACPTGSWKSH-UHFFFAOYSA-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 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 656.78, ALogP 5.5, HBA 7, HBD 3, PSA 137.73, QED 0.25
Compound (SMILES): O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(OCCO)cc3)cc12
InChIKey: YGKWXCWHOYVSAU-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y478
Assay: Allosteric activation of human AMPK alpha1/beta1/gamma1 by TR-FRET assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 331.76, ALogP 3.56, HBA 3, HBD 3, PSA 82.55, QED 0.67
Compound (SMILES): O=C(Nc1ccc([C@@H]2CNCCO2)cc1F)c1n[nH]c2cc(F)ccc12
InChIKey: XQQSAQSHEVFKOP-INIZCTEOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 358.35, ALogP 2.75, HBA 4, HBD 3, PSA 79.04, QED 0.67
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)cc1F)c1n[nH]c2cc(F)ccc12
InChIKey: XQQSAQSHEVFKOP-MRXNPFEDSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 358.35, ALogP 2.75, HBA 4, HBD 3, PSA 79.04, QED 0.67
Compound (SMILES): N#Cc1cccc(NC(=O)Nc2ccc([C@@H]3CNCCO3)cc2F)c1
InChIKey: WCEOEKIGWSVPFZ-KRWDZBQOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 340.36, ALogP 3, HBA 4, HBD 3, PSA 86.18, QED 0.8
Compound (SMILES): N#Cc1cccc(NC(=O)Nc2ccc([C@H]3CNCCO3)cc2F)c1
InChIKey: WCEOEKIGWSVPFZ-QGZVFWFLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 340.36, ALogP 3, HBA 4, HBD 3, PSA 86.18, QED 0.8
Compound (SMILES): N#Cc1cccc(NC(=O)Nc2ccc(C3CNCCO3)cc2Cl)c1
InChIKey: ZKAZLEUHOVSETO-UHFFFAOYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 356.81, ALogP 3.52, HBA 4, HBD 3, PSA 86.18, QED 0.78
Compound (SMILES): N#Cc1cccc(NC(=O)Nc2ccc([C@@H]3CNCCO3)cc2Cl)c1
InChIKey: ZKAZLEUHOVSETO-KRWDZBQOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 356.81, ALogP 3.52, HBA 4, HBD 3, PSA 86.18, QED 0.78
Compound (SMILES): O=C(Nc1ccc(Cl)nc1)Nc1ccc([C@@H]2CNCCO2)cc1F
InChIKey: YQNLPHPXFUGBHE-AWEZNQCLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 350.78, ALogP 3.18, HBA 4, HBD 3, PSA 75.28, QED 0.74
Compound (SMILES): O=C(Nc1ccc(Cl)nc1)Nc1ccc([C@H]2CNCCO2)cc1F
InChIKey: YQNLPHPXFUGBHE-CQSZACIVSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 350.78, ALogP 3.18, HBA 4, HBD 3, PSA 75.28, QED 0.74
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)nc1)Nc1ccc([C@@H]2CNCCO2)cc1F
InChIKey: MTXYCFXNJBJVPV-AWEZNQCLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 384.33, ALogP 3.54, HBA 4, HBD 3, PSA 75.28, QED 0.71
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)nc1)Nc1ccc([C@H]2CNCCO2)cc1F
InChIKey: MTXYCFXNJBJVPV-CQSZACIVSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 384.33, ALogP 3.54, HBA 4, HBD 3, PSA 75.28, QED 0.71
Compound (SMILES): O=C(Nc1ccc([C@@H]2CNCCO2)cc1F)c1ccn(-c2ccc(F)cc2)n1
InChIKey: PQWWTXORSYUPAA-IBGZPJMESA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 384.39, ALogP 3.06, HBA 5, HBD 2, PSA 68.18, QED 0.73