lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)N1c2ccc(-c3ccco3)cc2[C@H](NC(=O)OC(C)C)C[C@@H]1C
InChIKey: OZBRAEGGHPSXJE-SUMWQHHRSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of recombinant human BRD2 bromodomain 2 (342 to 460 residues) using biotin labeled peptide substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 356.42, ALogP 4.27, HBA 4, HBD 1, PSA 71.78, QED 0.89
Compound (SMILES): NC(=O)Cc1ccc(Nc2cc(C(F)(F)F)nc(-c3cccc(Cl)c3)n2)cc1
InChIKey: KRRGWHSEDYQKDQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Kinetic Assay: Assays are performed in 96-well plates in a total volume of 200 μl/well. Compounds are dissolved in dimethylsulfoxide (DMSO) and added to plates in a volume of 10 μl followed by addition of 165 μl of assay mix. Plates are pre-incubated at 25° C. for 15 min and the reactions are initiated by the addition of 25 μl of cAMP followed by thorough mixing. Reaction rates are measured by monitoring the decrease in fluorescence using excitation at 355 nm and emission at 460 nm for a period of 10 min in a fluorescence plate reader. Initial rates (slopes) are determined from linear portions of the progress curves. Final concentrations of assay components are as follows: 50 mM Tris, pH 8, 10 mM MgCl2, 50 mM KCl, 2% DMSO, 5 mM tris(2-carboxyethyl)phosphine (TCEP), 0.4 mM phosphenolpyruvate (PEP), 0.01 mM NADH, 0.04 mM adenosine triphosphate (ATP), 0.004 mM cAMP, 7.5 units myokinase from yeast, 1.6 units pyruvate kinase, 2 units lactate dehydrogenase, and either 0.5 nM human PDE4D7 or 10 nM human PDE4B1. All data are percent normalized relative to controls and are presented as percent inhibition. An inhibitory concentration 50% (IC50) value is calculated by fitting of a sigmoidal dose response curve. Human PDE4D7 contained a mutation of serine 54 to aspartic acid to mimic activation by cAMP-dependent protein kinase A (PKA). Human PDE4B1 contained a corresponding mutation of serine 133 to aspartic acid to also mimic PKA activation.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 406.8, ALogP 4.59, HBA 4, HBD 2, PSA 80.9, QED 0.65
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-c3c[nH]c4ccccc34)c12
InChIKey: YBBHADVVTLEPSZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: IC50 = 20.3 nM (pChEMBL 7.690000057220459)
Descriptors: MW 409.45, ALogP 5.54, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccc(NC(=O)CCOCc3ccccc3)cc2)n1
InChIKey: GCWJFCPMHSRKSB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR E746_A750 deletion/T790M mutant in human growth-resistant PC9 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 1670 nM (pChEMBL 5.78000020980835)
Descriptors: MW 603.12, ALogP 5.97, HBA 9, HBD 2, PSA 101.08, QED 0.19
Compound (SMILES): C[C@H](Oc1cccc(Cl)c1Cl)C(=O)Nc1ccc2oc(-c3ccc(CN)cc3)nc2c1
InChIKey: IXPNMEBSUPYMMX-ZDUSSCGKSA-N
Target: GMP reductase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2T1
Assay: Inhibition of human GMPR2 using GMP as substrate by spectrophotometric method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 456.33, ALogP 5.67, HBA 5, HBD 2, PSA 90.38, QED 0.39
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: HHBDPCCWQBHZLA-UYAOXDASSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins using 0.5 nM BMP1 by FRET based assay
Measurement: IC50 < 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 517.58, ALogP 3.67, HBA 7, HBD 4, PSA 158.41, QED 0.09
Compound (SMILES): Cl.N[C@@H]1CCC=C(c2ccc(F)cc2)[C@H]1CNc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl
InChIKey: LGCIKUFVGKSBFD-LJLRIERRSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 511.02, ALogP 5.11, HBA 6, HBD 3, PSA 97.11, QED 0.41
Compound (SMILES): O=C1C(c2ccccc2)N(S(=O)(=O)c2ccc(O)cc2)C(=O)C(c2ccccc2)N1S(=O)(=O)c1ccc(O)cc1
InChIKey: FZSXKKGJJJPNLY-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition and measured for 20 mins at 1 min interval by Ellman's method
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 578.62, ALogP 3.33, HBA 8, HBD 2, PSA 149.36, QED 0.35
Compound (SMILES): CC#C[C@@H](Cc1nnn[nH]1)c1ccc(OCc2ccc3scc(-c4ccc(OCC5(C)CS(=O)(=O)C5)cc4C)c3c2)cc1
InChIKey: NRDOHRGETHFOHC-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at rat GPR40 assessed as increase in intracellular calcium flux by cell based FLIPR assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 612.78, ALogP 6.13, HBA 8, HBD 1, PSA 107.06, QED 0.19
Compound (SMILES): C[C@H](Oc1cccc(F)c1F)C(=O)Nc1ccc2oc(-c3ccncc3)nc2c1
InChIKey: SUIPFGCLNNWIOP-LBPRGKRZSA-N
Target: GMP reductase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2T1
Assay: Inhibition of human GMPR2 using GMP as substrate by spectrophotometric method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 395.37, ALogP 4.57, HBA 5, HBD 1, PSA 77.25, QED 0.54
Compound (SMILES): O=C(NCCN1CCN(c2cccc(C(F)(F)F)c2)CC1)c1ccccn1
InChIKey: HBJPOHDQQVIBLT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]ketanserin from serotonin 5-HT2A receptor in Sprague-Dawley rat brain cortex homogenates incubated for 15 mins by liquid scintillation spectrometry
Measurement: Ki = 48.5 nM (pChEMBL 7.309999942779541)
Descriptors: MW 378.4, ALogP 2.65, HBA 4, HBD 1, PSA 48.47, QED 0.87
Compound (SMILES): Cl.FCCOc1cccc(CCC2CCN(CCc3ccccc3)CC2)c1
InChIKey: PZDFSTACALGBGX-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Inhibition of [3H]serotonin uptake at SERT in rat striatal synaptosomes preincubated for 5 mins followed by radioligand addition measured after 10 mins by scintillation spectrometry
Measurement: Ki = 2410 nM (pChEMBL 5.619999885559082)
Descriptors: MW 355.5, ALogP 4.92, HBA 2, HBD 0, PSA 12.47, QED 0.63
Compound (SMILES): CC(C)C[C@H](NC(=O)OC1CCN(S(C)(=O)=O)CC1)C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: POHZAMMIKLXFHR-ZOBUZTSGSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome-related coronavirus
UniProt: P0C6X7
Assay: Inhibition of SARS coronavirus 3CL protease using Dabcyl-KTSAVLQ/SGFRKME-Edans as substrate incubated for 30 mins followed by substrate addition measured after 1 hr by FRET assay
Measurement: IC50 = 28800 nM (pChEMBL 4.539999961853027)
Descriptors: MW 474.58, ALogP -0.24, HBA 7, HBD 3, PSA 150.98, QED 0.37
Compound (SMILES): Cc1c(NC(=O)c2ccc(C(C)(C)C)cc2)cccc1-c1nc(N)nc(Nc2ccc(C(=O)N3CCOCC3)cc2)n1
InChIKey: BRQYZNVVGDQNTM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal DYKDDDDK tagged biotinylated unactivated human recombinant BTK using FITC-labeled Srctide peptide substrate by by mobility shift assay
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 565.68, ALogP 5.2, HBA 8, HBD 3, PSA 135.36, QED 0.29
Compound (SMILES): Cl.Nc1ccc(OCc2ccccc2C(F)(F)F)cc1
InChIKey: FXFQYAAHTMLMNA-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using benzylamine as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by amplex red reagent based spectrophotometric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 267.25, ALogP 3.87, HBA 2, HBD 1, PSA 35.25, QED 0.86
Compound (SMILES): COc1cccc(F)c1-c1ccnc(Nc2ccc(S(=O)(=O)Nc3onc(C)c3C)cc2)n1
InChIKey: CIKHZDKMTDPCLM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human PLK1 kinase domain using 5-TAMRA-RGSFNDTLDFD-NH2 substrate and ATP incubated for 90 mins by fluorescent polarization assay
Measurement: IC50 = 12350 nM (pChEMBL 4.909999847412109)
Descriptors: MW 469.5, ALogP 4.44, HBA 8, HBD 2, PSA 119.24, QED 0.41
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCCCCCCNS(=O)(=O)c4cccc5c(N(C)C)cccc45)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CJDPJPUVKHWZHU-YRIIQKNPSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]-CHA from adenosine A2A receptor in rat striatal membranes
Measurement: Ki = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 640.77, ALogP 1.75, HBA 12, HBD 5, PSA 183.83, QED 0.13
Compound (SMILES): O=C(Nc1ccc(CP(=O)(O)O)cc1)C1CCN(C(=O)OCc2ccccc2)CC1
InChIKey: FLUJIZLIVFPWIW-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human ENPP2 using FS3 as substrate measured every 5 mins for 30 mins by fluorescence assay
Measurement: IC50 = 7.17 nM (pChEMBL 8.140000343322754)
Descriptors: MW 432.41, ALogP 3.35, HBA 4, HBD 3, PSA 116.17, QED 0.6
Compound (SMILES): O=C1CCc2c(Oc3ccc4c(c3)[C@@H]3[C@H](O4)[C@H]3c3nc4cc(C(F)(F)F)ccc4[nH]3)ccnc2N1
InChIKey: NGFFVZQXSRKHBM-FKBYEOEOSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Time-Resolved Fluorescence Energy Transfer Assay: Compounds disclosed herein were tested against B-Raf (V600E) (PV3849, from Invitrogen) or C-Raf (Y340D/Y341D) (PV3805, from Invitrogen) in a time-resolved fluorescence energy transfer assay. The assay was carried out in reactions (10 μL) containing 0.0625 nM B-Raf or 0.5 nM C-Raf, 25 mM Tris pH7.4, 10 mM MgCl2, 0.5 mM EGTA, 0.5 mM Na3BO4, 5 mM beta-glycerophosphate, 0.01% Triton X-100, 2.5 mM DTT, 0.1% BSA, 0.1 mM ATP, 13.7 nM GST-tagged MEK1 (Full-length protein with K97R mutation, recombinant protein purified from bacterial expression system) and 0-5 μM compounds disclosed herein (final concentration of 1% DMSO). The enzyme was incubated with the compounds at room temperature for 60 minutes and the reactions were initiated by the addition of ATP and GST-MEK1. After incubating at room temperature for 60 minutes, an equal volume of stop buffer containing 25 mM Tris pH7.4, 400 mM KF, 50 mM EDTA, 0.01% BSA, 0.01% Triton X-100, 1 test of Eu3+ Cryptate-conjugated rabbit polyclonal antibody anti-Phospho MEK1/2 (Ser217/221) and 1 test of d2-conjugated mouse monoclonal antibody anti-glutathione S-transferase was added to stop the reactions. Plates were sealed and incubated at room temperature for 2 hours, and then the TR-FRET signals were read on BMG PHERAstar FS instrument.
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 478.43, ALogP 5.3, HBA 5, HBD 2, PSA 89.13, QED 0.42
Compound (SMILES): CC(=O)Nc1cn2cc(-c3cc(NC(=O)c4cccc(C(F)(F)F)n4)ccc3C)ccc2n1
InChIKey: AOLMTMCVLOTZFR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 453.42, ALogP 4.93, HBA 5, HBD 2, PSA 88.39, QED 0.46
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(C2CCOCC2)nc(N2CCN(S(C)(=O)=O)CC2)n1
InChIKey: LRNAFJHUEUYKJR-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His-tagged human PI3K p110beta/p85alpha expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 523.57, ALogP 2.13, HBA 10, HBD 0, PSA 115.57, QED 0.48
Compound (SMILES): Cn1cc(-c2ccc(=O)n(CCOc3ccnc4cc(OCCCCCCC(=O)NO)ccc34)n2)cn1
InChIKey: CPSLMXLQONGQGR-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human full length HDAC1 expressed in baculovirus infected Sf9 insect cells using biotinylated lysine 9 acetylated histone H3 (1 to 21 residues) as substrate incubated for 5 mins followed by substrate addition measured after 60 mins by HTRF assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 506.56, ALogP 3.11, HBA 10, HBD 2, PSA 133.39, QED 0.16
Compound (SMILES): c1cncc(-n2cnc3c(NCc4nc5ccccc5[nH]4)nc(N4CCOCC4)nc32)c1
InChIKey: MRBCMMFFSDIHIK-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 2095 nM (pChEMBL 5.679999828338623)
Descriptors: MW 427.47, ALogP 2.54, HBA 9, HBD 2, PSA 109.67, QED 0.44
Compound (SMILES): N#CSCCCCCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: MMPNVOZVVJPJMK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Mixed-type inhibition of equine serum BuChE assessed as enzyme-inhibitor complex using p-nitrophenyl butyrate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 252 nM (pChEMBL 6.599999904632568)
Descriptors: MW 339.51, ALogP 5.3, HBA 4, HBD 1, PSA 48.71, QED 0.52
Compound (SMILES): O=S(=O)(Nc1ncns1)c1cc(F)c(OC2OCCNC2c2ccc(Cl)nc2)cc1F
InChIKey: XUXADYQVXIOPJZ-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Antagonist activity at recombinant human Nav1.7 expressed in HEK293 cells assessed as reduction in channel current at -60 mV holding potential after 600 secs by barracuda automated electrophysiology method
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 489.91, ALogP 2.73, HBA 9, HBD 2, PSA 115.33, QED 0.51
Compound (SMILES): O=[N+]([O-])c1ccc2oc3nccc(NCc4ccc(Br)cc4)c3c2c1
InChIKey: SGOKBBMPHMZOQX-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of recombinant human GST-tagged IGF1R expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr) 4:1 as substrate after 60 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: Ki = 2870 nM (pChEMBL 5.539999961853027)
Descriptors: MW 398.22, ALogP 5.26, HBA 5, HBD 1, PSA 81.2, QED 0.37
Compound (SMILES): CNC(=O)c1cc(OCCCCN2CCN(c3cccc4sccc34)CC2)ccn1
InChIKey: AOSUTZCGNCJEJR-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonistic activity at human dopamine D2 receptor measured after 60 mins by Lance Ultra cAMP assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 424.57, ALogP 3.64, HBA 6, HBD 1, PSA 57.7, QED 0.56
Compound (SMILES): Cn1cc(-c2ccc(=O)n(CCOc3ccnc4cc(-c5ccc(C(=O)Nc6ccccc6N)s5)ccc34)n2)cn1
InChIKey: GIGLKJOCNUGOJM-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human full length HDAC1 expressed in baculovirus infected Sf9 insect cells using biotinylated lysine 9 acetylated histone H3 (1 to 21 residues) as substrate incubated for 5 mins followed by substrate addition measured after 60 mins by HTRF assay
Measurement: IC50 = 467 nM (pChEMBL 6.329999923706055)
Descriptors: MW 563.64, ALogP 4.83, HBA 10, HBD 2, PSA 129.95, QED 0.25
Compound (SMILES): CC(C)=CCC/C(C)=C/COc1ccc2oc3cc(O)cc(O)c3c(=O)c2c1
InChIKey: WOPKDKPJTJHLPB-OQLLNIDSSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of recombinant human PTP1B (1 to 322 residues) expressed in Escherichia coli using P-NPP as substrate after 10 mins by Dixon plot analysis
Measurement: Ki = 19900 nM (pChEMBL 4.699999809265137)
Descriptors: MW 380.44, ALogP 5.43, HBA 5, HBD 2, PSA 79.9, QED 0.44
Compound (SMILES): CCC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC3CCCC3)nc2N1C1CCCC1
InChIKey: QIWKCZYPLMKZJX-HHHXNRCGSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human recombinant PLK1 by Z-Lyte assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 589.79, ALogP 5.26, HBA 8, HBD 2, PSA 102.93, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)C2CCn3c(C(=O)c4ccccc4)ccc32)cc1
InChIKey: PMIJIUBQPGGGSW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase-2 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 409.47, ALogP 2.49, HBA 5, HBD 2, PSA 111.26, QED 0.63
Compound (SMILES): CCN1C(=O)C(c2ccccc2)Oc2cc3c(cc21)OCO3
InChIKey: SLDCLTXGVNYDKR-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His-tagged GSK3beta using GS-2 peptide as substrate in presence of [33P]gamma-ATP after 15 mins by microbeta counting method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 297.31, ALogP 2.9, HBA 4, HBD 0, PSA 48, QED 0.85
Compound (SMILES): Cc1ccc(NC(=O)c2coc3ccccc3c2=O)cc1C
InChIKey: WDCZOLPCRVTBPH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Mixed-type inhibition of recombinant human MAO-B expressed in Pichia pastoris using benzylamine as substrate by fluorimetric horseradish peroxidase-Amplex Red-coupled assay
Measurement: Ki = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 293.32, ALogP 3.66, HBA 3, HBD 1, PSA 59.31, QED 0.78
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)C(C)N(C)CCN3S(C)(=O)=O
InChIKey: FBUXXVMAYBMPQM-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 445.52, ALogP 3.37, HBA 5, HBD 1, PSA 82.86, QED 0.67
Compound (SMILES): Clc1cc2nc(CNc3nc(N4CCNCC4)nc4c3ncn4-c3cccnc3)[nH]c2cc1Cl
InChIKey: NFGOADORCRMUJZ-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 495.38, ALogP 3.42, HBA 9, HBD 3, PSA 112.47, QED 0.34
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(Cl)c12
InChIKey: CODMIPQTVMYKBE-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: IC50 = 1760 nM (pChEMBL 5.75)
Descriptors: MW 328.76, ALogP 4.04, HBA 5, HBD 1, PSA 76.83, QED 0.56
Compound (SMILES): CC(C)N(NC(=O)c1ccc2ccccc2c1)C(=O)C1CCC[C@H]1C(=O)N[C@H]1CC(=O)OC1O
InChIKey: DJLYWTRDUYITDZ-WKRUFEFESA-N
Target: Caspase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29466
Assay: Inhibition of human recombinant caspase-1 using AC-WEHD-AMC as substrate at Km after 20 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.52, ALogP 1.89, HBA 6, HBD 3, PSA 125.04, QED 0.46
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2cc(F)c(=O)n(C)c2)c1)c1ccccc1
InChIKey: CFBUFBFJMBWHPM-BJKOFHAPSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transactivation activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 512.53, ALogP 4.78, HBA 6, HBD 1, PSA 78.15, QED 0.37
Compound (SMILES): CCCc1nc(C)c2c(=O)[nH]c(-c3cc(-c4ccc(C(=O)NO)cc4)ccc3OCC)nn12
InChIKey: OQSYENMWQGYXMW-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant C-terminal His-tagged HDAC2 expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 30 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 447.5, ALogP 3.53, HBA 7, HBD 3, PSA 121.61, QED 0.29
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCOC2CN(Cc3cccnc3)CC(N3CCCC3)C21
InChIKey: NMHBJNRIZGIDFC-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P97266
Assay: Displacement of [3H]DAMGO from mu opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 633 nM (pChEMBL 6.199999809265137)
Descriptors: MW 489.45, ALogP 3.51, HBA 5, HBD 0, PSA 48.91, QED 0.64
Compound (SMILES): O=C(O)CCC(=O)N(C1CC1)C1c2ccccc2N(C(=O)OCc2ccccc2)C2CCCCC21
InChIKey: HRQNFEGHBNZHPV-UHFFFAOYSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity at human CRTh2 expressed in HEK cells assessed as inhibition of DK-PGD2-mediated attenuation of forskolin-induced intracellular cAMP accumulation preincubated for 10 mins followed by forskolin stimulation measured after 10 to 60 mins by ELISA based chemiluminescence assay
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 476.57, ALogP 5.3, HBA 4, HBD 1, PSA 87.15, QED 0.59
Compound (SMILES): CCOc1cc(=O)[nH]cc1-c1ccc(CC(=O)Nc2cc(C(F)(F)F)cc(CN(C)C)c2F)c(F)c1
InChIKey: ATVKDEADBYCHSW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human KDR using cisbio TK biotin-peptide as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by HTRF assay
Measurement: IC50 = 1830.3 nM (pChEMBL 5.739999771118164)
Descriptors: MW 509.48, ALogP 4.98, HBA 4, HBD 2, PSA 74.43, QED 0.42
Compound (SMILES): CS(=O)(=O)N1CCN(C(=O)c2cnc3ccc(F)cc3c2N2CCC3(CC2)C(=O)Cc2ccccc23)CC1
InChIKey: KYCJMCTWZQDMRF-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 536.63, ALogP 2.75, HBA 6, HBD 0, PSA 90.89, QED 0.51
Compound (SMILES): CC(C)c1ccc(CC(=O)NCc2ccn(Cc3ccc(F)c(F)c3)n2)cc1
InChIKey: WESARZWFBOCZMD-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1I (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0X4
Assay: Inhibition of recombinant Cav3.3 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 383.44, ALogP 4.19, HBA 3, HBD 1, PSA 46.92, QED 0.66
Compound (SMILES): COc1ccc2ccccc2c1/C=N/NC(=O)c1ccc(-c2ccccc2)cc1
InChIKey: IGKNGGYVNFAQNB-YZSQISJMSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase RNase H using RNA-DNA hybrid duplex after 30 mins by FRET-based microplate fluorescence assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 380.45, ALogP 5.28, HBA 3, HBD 1, PSA 50.69, QED 0.38
Compound (SMILES): CCc1nn2c(C)cc(C)nc2c1Cc1ccc(/C=C/CN2CCN(C(C)C)CC2)cc1
InChIKey: CSQZLIGLFJJGNT-BQYQJAHWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG expressed in HEK293 cell membranes after 90 mins by liquid scintillation counting method
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 431.63, ALogP 4.54, HBA 5, HBD 0, PSA 36.67, QED 0.55
Compound (SMILES): CC(C)NC(=O)N[C@H]1CC[C@H](Nc2nc(N[C@H](C)CO)nc3ccc(-c4cccc(F)c4)cc23)CC1
InChIKey: ATZLHDZWWHBJEQ-ZPMCFJSWSA-N
Target: Atrial natriuretic peptide receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P16066
Assay: Agonist activity at human NPR-A expressed in CHO cells assessed as increase in cGMP accumulation after 30 mins by radioimmunoassay
Measurement: EC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 494.62, ALogP 4.66, HBA 6, HBD 5, PSA 111.2, QED 0.31
Compound (SMILES): Cn1ncc2c(=O)n(Cc3ccccc3)c(SCc3cccc(F)c3)nc21
InChIKey: BLZOLNGGJICKAZ-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 380.45, ALogP 3.61, HBA 6, HBD 0, PSA 52.71, QED 0.39
Compound (SMILES): Cc1ccn(-c2ccc(C(=O)N3CCCCCC3)c(Cl)c2)n1
InChIKey: HJBOAPCMBLXZDQ-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Displacement of [3H]-AVP from human V2 receptor expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 317.82, ALogP 3.85, HBA 3, HBD 0, PSA 38.13, QED 0.84
Compound (SMILES): COc1cc2c(NC3C4CCC3CN(C)C4)cc(-c3ccc(C)o3)nc2cc1OC1CC2(C1)CN(C)C2
InChIKey: BXULHRSCDMZOIM-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human DNMT1 using polydeoxyinosine polydeoxycytosine DNA as substrate after 15 mins in presence of SAM by TR-FRET assay
Measurement: IC50 = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 502.66, ALogP 5.04, HBA 7, HBD 1, PSA 63, QED 0.51
Compound (SMILES): COc1ccc2c(c1)c(CCNCCCc1cccc(C(F)(F)F)c1)cn2C
InChIKey: LHSIWTJBWFNAPJ-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]-DHA from Nb69-fused beta2 adrenergic receptor (unknown origin) expressed in Sf9 cell membranes after 2 hrs by microbeta scintillation counting method
Measurement: Ki = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 390.45, ALogP 4.97, HBA 3, HBD 1, PSA 26.19, QED 0.55
Compound (SMILES): CC(C)COc1ccccc1CNC(=O)c1c(Cl)c(C2CC2)c(Cl)n1C
InChIKey: IPZSSERKZYFAEE-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 395.33, ALogP 5.17, HBA 3, HBD 1, PSA 43.26, QED 0.7
Compound (SMILES): Fc1ccc(-c2n[nH]c3c2CCNCC3)cc1
InChIKey: YOZGUJJGVBYZQY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]LSD from human 5-HT7 receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method
Measurement: Ki = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 231.27, ALogP 1.9, HBA 2, HBD 2, PSA 40.71, QED 0.79
Compound (SMILES): CCc1cccc(-c2c(F)cccc2C(O)(CCCNC(=O)OC)[C@@H]2CCCN(C(=O)CC[C@H](N)C(=O)OC)C2)c1
InChIKey: UWTPQSLKZKEZLQ-ZQMDHAFISA-N
Target: Renin (SINGLE PROTEIN), Homo sapiens
UniProt: P00797
Assay: Inhibition of renin in human plasma using angiotensinogen as substrate measured for 90 mins by [125I]-angiotensin based radioimmunoassay
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 571.69, ALogP 3.9, HBA 7, HBD 3, PSA 131.19, QED 0.26
Compound (SMILES): Cc1nc(C)c(COc2ccc(/C=C/C(=O)NCCCCNc3c4c(nc5ccccc35)CCCC4)cc2OCc2nc(C)c(C)nc2C)nc1C
InChIKey: WPOHYZVTLFECNA-CZIZESTLSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BCHE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by DTNB addition for 5 mins and subsequent addition of substrate measured after 3 mins by Ellman's method
Measurement: IC50 = 110.9 nM (pChEMBL 6.960000038146973)
Descriptors: MW 699.9, ALogP 7.72, HBA 9, HBD 2, PSA 124.04, QED 0.09
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)NC(C)C)c12
InChIKey: BEKSUJBQAFPFQK-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 301.39, ALogP 2.56, HBA 5, HBD 3, PSA 92.93, QED 0.71
Compound (SMILES): Cl.O=C(O)CN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3Cl)ccc12
InChIKey: ALUHPICSWDTBNJ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at human S1P1 receptor expressed in CHO cells assessed as increase in calcium flux by aequorin-derived luminescence assay
Measurement: EC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 422.31, ALogP 4.38, HBA 4, HBD 1, PSA 59, QED 0.78
Compound (SMILES): COc1ccccc1C1CN(C(=O)c2sc3nnc(C)c(C)c3c2N)C1
InChIKey: NNHDUKMWAHHKKT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of human M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 2290.87 nM (pChEMBL 5.639999866485596)
Descriptors: MW 368.46, ALogP 3.14, HBA 6, HBD 1, PSA 81.34, QED 0.77
Compound (SMILES): CNc1nc(Nc2ccc(-n3cnc(C)n3)c(OC)c2)nc2c1CC[C@H]2c1ccc(F)cc1
InChIKey: NDVMOVOEROCRIO-SFHVURJKSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of gamma-secretase (unknown origin) assessed as inhibition of amyloid beta 42 production
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 445.5, ALogP 4.38, HBA 8, HBD 2, PSA 89.78, QED 0.46
Compound (SMILES): CC1CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(C)CC6)cn5)ncc4F)cc3n21
InChIKey: DNURQZGRRIHXKJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin) after 90 mins by ADP-Glo assay
Measurement: IC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 490.56, ALogP 4.16, HBA 8, HBD 1, PSA 75, QED 0.45
Compound (SMILES): CCOC(=O)C1=C(C)NC(=S)NC1c1ccccc1C
InChIKey: NJYQSMOEYIEVEN-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 using p-nitrophenylacetate as substrate measured at 3 mins interval by spectrophotometric method
Measurement: Ki = 30.63 nM (pChEMBL 7.510000228881836)
Descriptors: MW 290.39, ALogP 2.35, HBA 3, HBD 2, PSA 50.36, QED 0.66
Compound (SMILES): COc1ccc(Cl)cc1S(=O)(=O)Nc1cncc(-c2ccc(Cl)cc2)c1
InChIKey: RIJNYZFHPZMXQB-UHFFFAOYSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Enzyme Kinetic Assay: To determine the inhibition selectivity for inhibitor candidates, human TNAP, PLAP or IAP were added to microtiter plates followed by addition of the substrate pNPP (0.5 mM) and activity was measured in 1 M DEA-HCl buffer, pH 9.8 or in 1 M Tris-HCl buffer, pH 7.5, containing 1 mM MgCl2 and 20 μM ZnCl2, in the presence of potential inhibitors (0-30 μM). TNAP, PLAP and IAP activities were adjusted to an approximate λA405 nm, equivalent to 1, measured after 30 min. Residual AP activity in the presence of inhibitors was expressed as percentage of the control activity. To investigate the mechanism of inhibition, double reciprocal plots of enzyme activity (expressed as mA405 nm min−1) vs. substrate concentration were constructed, in the presence of various concentrations of added inhibitors (0-30 μM). The y-axis intercepts of the 1/v vs. 1/[S] plots, were then plotted vs. [I] to graphically extract Ki values as the x-intercept in this plot. The numerical values from y- and x-intercepts were derived via linear regression analysis, using software Prism 3.02 (GraphPad Software, CA). These analyses were performed, using pNPP as a substrate in 1 M DEA-HCl buffer, pH 9.8, as well as in 1 M Tris-HCl buffer, pH 7.5, to determine Ki at optimal and physiological pH respectively. Inhibitors were further tested and sorted based on their kinetic properties at pH 7.4 using PPi, the relevant natural substrate of TNAP. In this part of the study, pyrophosphate sodium salt (99% ACS reagent, Sigma-Aldrich, St Louis, Mo.) was used as a substrate. Amounts of released phosphate were measured using the Biomol Green Reagent (Biomol Research Laboratories, Inc., Plymouth Meeting, Pa.). Finally, to document the potency of selected inhibitors in physiological media, TNAP inhibition by compounds of Formula I-IV (0-30 μM) was studied at pH 7.4, during catalysis of 0.1 mM pNPP, in the presence of increasing concentrations of Na2HPO4 (0-10 mM) and pyrophosphate (0-40 mM).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 409.29, ALogP 4.86, HBA 4, HBD 1, PSA 68.29, QED 0.65
Compound (SMILES): N#C[Se]CCCCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: AJTMZVVUIMONJA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Competitive inhibition of electric eel AChE assessed as enzyme-inhibitor complex using p-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 372.37
Compound (SMILES): CC1(C)CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCNCC6)cn5)ncc4F)cc3n21
InChIKey: DHPLYCJQWJHXFH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/ G1/S-specific cyclin-D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full length CDK1/Cyclin D3 expressed in baculovirus infected Sf9 insect cells using histone H1 substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 1365 nM (pChEMBL 5.869999885559082)
Descriptors: MW 490.56, ALogP 4, HBA 8, HBD 2, PSA 83.79, QED 0.44
Compound (SMILES): COc1ccc(C2=NN(C3CCCCCC3)C(=O)[C@@H]3CC=CC[C@H]23)cc1-c1ccc(C(=O)NCCC(N)=O)cc1
InChIKey: LQRHIYIFVVRJJY-IZZNHLLZSA-N
Target: Class 1 phosphodiesterase PDEB1 (SINGLE PROTEIN), Trypanosoma brucei
UniProt: Q8WQX9
Assay: Inhibition of full length Trypanosoma brucei PDEB1 expressed in Sf21 insect cells using cAMP as substrate by scintillation proximity assay
Measurement: Ki = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 542.68, ALogP 4.82, HBA 5, HBD 2, PSA 114.09, QED 0.37
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)[C@@H](C)O[C@@H](CS(C)(=O)=O)CN3S(C)(=O)=O
InChIKey: PCQOPPOYJPHFQB-CZUORRHYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 1208 nM (pChEMBL 5.920000076293945)
Descriptors: MW 524.59, ALogP 2.87, HBA 7, HBD 1, PSA 122.99, QED 0.54
Compound (SMILES): C[C@H](Oc1cccc(Cl)c1Cl)C(=O)Nc1ccc2oc(-c3cccc(OCC(=O)O)c3)nc2c1
InChIKey: ZXUBFAMLQIJLAG-ZDUSSCGKSA-N
Target: GMP reductase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2T1
Assay: Inhibition of human GMPR2 using GMP as substrate by spectrophotometric method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 501.32, ALogP 5.67, HBA 6, HBD 2, PSA 110.89, QED 0.32
Compound (SMILES): CC[C@H](NC(=O)C(F)(F)F)[C@H](Oc1ccc(C#N)cc1Br)c1cnc(C2CC2)nc1
InChIKey: XGORDNAQWNGCSW-DOTOQJQBSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transactivation activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: EC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 483.29, ALogP 4.57, HBA 5, HBD 1, PSA 87.9, QED 0.62
Compound (SMILES): C=CC(=O)NC1CCc2c(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc3n2C1
InChIKey: IZIKXPZHFAJJMS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human BTK using Poly(Glu, Tyr) 4:1 as substrate after 1 hr by ELISA
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 425.49, ALogP 4.09, HBA 6, HBD 2, PSA 95.06, QED 0.47
Compound (SMILES): COc1ccc(-c2nc3cc(NC(=S)[C@H](C)Oc4cccc(Cl)c4Cl)ccc3o2)cc1
InChIKey: KWVHWILLIXCGQS-ZDUSSCGKSA-N
Target: GMP reductase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2T1
Assay: Inhibition of human GMPR2 using GMP as substrate by spectrophotometric method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 473.38, ALogP 7.02, HBA 5, HBD 1, PSA 56.52, QED 0.3
Compound (SMILES): CCN1CCc2nc(Nc3cc(-c4cc(F)c5nc(C)n(C(C)C)c5c4)ncn3)ccc2C1
InChIKey: YDTIWHFPTISVND-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of human CDK1/Cyclin-B using ULight-substrate after 1 hr by LANCE assay
Measurement: IC50 = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 445.55, ALogP 5.04, HBA 7, HBD 1, PSA 71.76, QED 0.46
Compound (SMILES): COc1ccccc1[C@]12CO[C@@H](C)C[C@H]1CSC(N)=N2
InChIKey: SPCKMVYZWVCNSY-PGUXBMHVSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of Cathepsin D (unknown origin) by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 292.4, ALogP 2.38, HBA 5, HBD 1, PSA 56.84, QED 0.91
Compound (SMILES): COc1cccc(F)c1-c1ccnc(Nc2ccc(S(=O)(=O)Nc3nnc(C)s3)cc2)n1
InChIKey: LRXZVWVFJCSXSV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human PLK1 kinase domain using 5-TAMRA-RGSFNDTLDFD-NH2 substrate and ATP incubated for 90 mins by fluorescent polarization assay
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 472.53, ALogP 4, HBA 9, HBD 2, PSA 118.99, QED 0.41
Compound (SMILES): COc1cncc2c(-c3nn(C4CCOCC4)c4c3CN(C(C)=O)CC4)cccc12
InChIKey: GAVVBDXGDAIREU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain 1 (unknown origin) by TR-FRET assay
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 406.49, ALogP 3.36, HBA 6, HBD 0, PSA 69.48, QED 0.67
Compound (SMILES): CCC1(C#N)CCN(c2c(C(=O)N3CCN(C(=O)C4CC4)CC3)cnc3ccc(F)cc23)CC1
InChIKey: WWNYGWVXNBKAJJ-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 463.56, ALogP 3.59, HBA 5, HBD 0, PSA 80.54, QED 0.69
Compound (SMILES): CC(=O)N1CCc2c(c(-c3cccc4cc(-c5cn(C)nc5C(F)F)ncc34)nn2C2CCOCC2)C1
InChIKey: FOEXHUHDGDFWNT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain 1 (unknown origin) by TR-FRET assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 506.56, ALogP 4.69, HBA 7, HBD 0, PSA 78.07, QED 0.4
Compound (SMILES): CN1CCN(C2CCN(c3n[nH]c(N)n3)CC2)[C@@H](Cc2ccc(Cl)cc2)C1
InChIKey: BYCLUAVYESDINX-KRWDZBQOSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D7Q1
Assay: Inhibition of mouse CHIT1 using 4-methylumbelliferyl beta-D-N,N',N'' triacetylchitotrioside as substrate measured after 60 mins by fluorometric method
Measurement: IC50 = 1590 nM (pChEMBL 5.800000190734863)
Descriptors: MW 389.94, ALogP 1.87, HBA 6, HBD 2, PSA 77.31, QED 0.83
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N(C)C2CN(S(C)(=O)=O)C2)n1
InChIKey: XITRAJOKTSFGKQ-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His-tagged human PI3K p110beta/p85alpha expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 = 282 nM (pChEMBL 6.550000190734863)
Descriptors: MW 524.55, ALogP 1.07, HBA 11, HBD 0, PSA 118.81, QED 0.44
Compound (SMILES): CN(C)c1ccc(CC(=O)Nc2ccn(Cc3ccc(OC(F)F)cc3)n2)cc1
InChIKey: KEVRFMSQVMILBS-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 400.43, ALogP 3.78, HBA 5, HBD 1, PSA 59.39, QED 0.63
Compound (SMILES): CCCOc1nc2c(c(=O)n(C)c(=O)n2C)n1CCCC(=O)N/N=C/c1ccccc1
InChIKey: BMDXRMSXXQGYQL-HYARGMPZSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition of human GST-tagged PDE7A expressed in baculovirus infected Sf9 insect cells using cAMP as substrate after 10 mins by PDE-Glo Phosphodiesterase Assay
Measurement: IC50 = 92900 nM (pChEMBL 4.03000020980835)
Descriptors: MW 426.48, ALogP 1.15, HBA 9, HBD 1, PSA 112.51, QED 0.41
Compound (SMILES): NS(=O)(=O)c1cccc(/N=C2\NC(=O)/C(=C3/C(=O)N(Cc4ccccc4)c4ccccc43)S2)c1
InChIKey: YHOPAXPQWMGSQU-MRCUWXFGSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic carbonic anhydrase 2 by stopped-flow CO2 hydrase assay
Measurement: Ki = 18.2 nM (pChEMBL 7.739999771118164)
Descriptors: MW 490.57, ALogP 3.14, HBA 6, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1cccc(NC(=O)c2cc(C(=O)c3cncnc3)cc3cccnc23)n1
InChIKey: MDNZTYQRDWFDBJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Negative allosteric modulator activity at rat mGlu5 receptor expressed in HEK293A cells assessed as inhibition of EC80 glutamate-induced Ca2+ mobilization by Fluo-4 AM dye based fluorescence assay
Measurement: IC50 = 416.87 nM (pChEMBL 6.380000114440918)
Descriptors: MW 369.38, ALogP 3.21, HBA 6, HBD 1, PSA 97.73, QED 0.55
Compound (SMILES): COc1ccc(C2CCN(C(=O)Cc3ccccc3Cl)C2)cc1
InChIKey: UCTRIAJPESVHOK-UHFFFAOYSA-N
Target: Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q6GI75
Assay: Competitive inhibition of Staphylococcus aureus subsp. aureus Rosenbach ATCC 43300 FabI using crotonyl-CoA as substrate in presence of NADPH/NADH after 10 mins by fluorescence assay
Measurement: Ki = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 329.83, ALogP 3.91, HBA 2, HBD 0, PSA 29.54, QED 0.85
Compound (SMILES): Cc1ccc2c(c1)/C(=C1/S/C(=N/c3ccc(S(N)(=O)=O)cc3)NC1=O)C(=O)N2
InChIKey: WBFWASSTCOJLCZ-PFONDFGASA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic carbonic anhydrase 2 by stopped-flow CO2 hydrase assay
Measurement: Ki = 57.4 nM (pChEMBL 7.239999771118164)
Descriptors: MW 414.47, ALogP 1.86, HBA 6, HBD 3, PSA 130.72, QED 0.65
Compound (SMILES): CC(=O)c1c(OCCCN2CCN(c3ccccc3Cl)CC2)ccc2c(C)cc(=O)oc12
InChIKey: MLBJSKCPQRFALF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor expressed in CHO-K1 cell membranes after 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 454.95, ALogP 4.55, HBA 6, HBD 0, PSA 62.99, QED 0.3
Compound (SMILES): COCC(C)Oc1ccc(N2CCN(CCn3c(=O)n(C)c4c3nc(N)n3nc(-c5ccco5)nc43)CC2)cc1
InChIKey: HURASBAMXINLCB-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at human A2A receptor expressed in HEK293 cell membranes assessed as reduction in CGS-21680-induced cAMP level pretreated for 15 mins followed by CGS-21680 addition measured after 30 mins by HTRF assay
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 547.62, ALogP 1.86, HBA 13, HBD 1, PSA 134.11, QED 0.29
Compound (SMILES): Cc1n[nH]cc1-c1cc2c(s1)C(=O)N[C@]1(CC[C@](O)(C3CCCCC3)CC1)N2
InChIKey: JEMZAKZZKHRMHZ-OYRHEFFESA-N
Target: CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBU7
Assay: Inhibition of recombinant human Cdc7 (1 to 574 residues)/human N-terminal GST-tagged DBF4 (1 to 674 residues) expressed in baculovirus expression system using His-tagged MCM2 as substrate preincubated for 10 mins followed by ATP addition by HTRF assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 400.55, ALogP 4.18, HBA 5, HBD 4, PSA 90.04, QED 0.61
Compound (SMILES): CCNCC(=O)Nc1ccc2nc3n(c(=O)c2c1)CCC3
InChIKey: KKAIOBSUMOSSIY-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE pre-incubated for 6 mins before ATCI substrate addition and measured after 12 mins by DTNB reagent dependent UV-Vis spectrophotometry based Ellman's method
Measurement: IC50 = 557 nM (pChEMBL 6.25)
Descriptors: MW 286.33, ALogP 0.89, HBA 5, HBD 2, PSA 76.02, QED 0.87
Compound (SMILES): O=C(c1ccc(Cl)cc1)N1CCCCc2ccccc21
InChIKey: TUHHRVOIMGMMSL-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Displacement of [3H]-AVP from human V2 receptor expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki = 507 nM (pChEMBL 6.289999961853027)
Descriptors: MW 285.77, ALogP 4.32, HBA 1, HBD 0, PSA 20.31, QED 0.76
Compound (SMILES): C=CC(=O)N1CC[C@@H](n2nc(-c3ccc(Oc4cccc(OC)c4Cl)cc3)c3cnccc32)C1
InChIKey: RFMOLOQORONTNN-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinases Assay : Btk kinase activity was determined using a homogenous time resolved fluorescence (HTRF) methodology. Measurements were performed in a reaction volume of 15 μL using 384-well assay plates. Kinase enzyme, inhibitor, ATP and 1 μM peptide substrate were incubated in a reaction buffer compose of Hepes50 mM (pH7.0), NaN3 0.02%, BSA 0.01%, Orthocanadate 0.1 mM. After one hour, the kinase reaction was quenched by the addition of E t-labeled antibody and XL-665 in 1×Detection buffer containing 60 mM EDTA (Cisbio), and the mixture was allowed to incubate for one hour. The HTRF signal was measured on a multimode plate reader (EnVision Multilabel Reader, Perkin Elmer) with an excitation wavelength (λEx) of 330 nm and detection wavelengths (λEm) of 615 and 665 nm. Activity was determined by the ratio of the fluorescence at 665 nm to that at 615 nm. For each compound, enzyme activity as measured at various concentrations of compound, Negative control reactions were performed in the absence of inhibitor in two replicates and eight no enzyme controls were used to determine baseline fluorescence levels. IC50s were obtained according to the equation:Y=100/(1+10{circumflex over ( )}((Log IC50−X)*HillSlope)).For BTK assay, [ATP]=80 μM, BTK=3.4 nM.For LYN assay, [ATP]=20 μM, LYN=0.12 n M. For LCK assay, [ATP]=20 μM, LCK=0.2 nM. For BLK assay, [ATP]=20 μM, BLK=0.6 n M.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 474.95, ALogP 5.51, HBA 6, HBD 0, PSA 69.48, QED 0.34