lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)[C@H]2CC[C@H](O)CC2)C(=O)N[C@@H](Cc2ccccc2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: DMAYUUDCUFRNPK-JTRPPKJJSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of 20S proteosome beta 1 in human MOLT4 cells by ELISA
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 579.69, ALogP 1.86, HBA 7, HBD 4, PSA 146.36, QED 0.27
Compound (SMILES): CCc1ccc(S(=O)(=O)Nc2ccc3oc(-c4ccccc4)nc3c2)cc1
InChIKey: YAIHXAATRHGATA-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 378.45, ALogP 4.86, HBA 4, HBD 1, PSA 72.2, QED 0.54
Compound (SMILES): NS(=O)(=O)c1ccc(-c2noc(-c3ccccc3)n2)cc1
InChIKey: VVLWDIHRZMTIJU-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as reduction in CO2 hydration after 15 mins by phenol red staining-based stopped flow assay
Measurement: Ki = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 301.33, ALogP 2.05, HBA 5, HBD 1, PSA 99.08, QED 0.8
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc2ccccc2c1)CC1CC1c1cc(F)ccc1OC.Cl
InChIKey: BPLXRWXQBOJQFF-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D4 receptor stably expressed in HEK cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 844 nM (pChEMBL 6.070000171661377)
Descriptors: MW 462.61, ALogP 6.01, HBA 3, HBD 1, PSA 41.57, QED 0.34
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(OCC5CC5)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: FVHKTXLAWSFSNK-GOSISDBHSA-N
Target: IKK epsilon/TBK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of IKKepsilon/TBK1 in human MDB-MB-231 cells transduced with lentiviral vector expressing human IRF3 assessed as decrease in poly(I:C)-stimulated IRF3 phosphorylation at S385/386 residues preincubated for 1 hr followed by poly(I:C) addition and measured after 1 hr
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 580.62, ALogP 5.1, HBA 8, HBD 2, PSA 112.16, QED 0.28
Compound (SMILES): CCN(CC)CCCCOc1ccc(/C=C/C(=O)c2ccc(OCCCCN(CC)CC)cc2O)cc1
InChIKey: YXLQQCOCUUYTIW-HMMYKYKNSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence based assay
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 510.72, ALogP 6.29, HBA 6, HBD 1, PSA 62.24, QED 0.14
Compound (SMILES): NC(=O)c1cccc2c1O/C(=C\c1ccc(-c3nn[nH]n3)cc1)C2=O
InChIKey: QYXDDRWHQGGYKR-JYRVWZFOSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 = 2.042 nM (pChEMBL 8.6899995803833)
Descriptors: MW 333.31, ALogP 1.58, HBA 6, HBD 2, PSA 123.85, QED 0.7
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: HVTMEGQWQQUDIH-DCAYLYCYSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta2/beta3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12391
Assay: Antagonist activity at rat alpha6alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 0.99 nM (pChEMBL 9)
Descriptors: MW 1701.96
Compound (SMILES): COc1ccccc1C1C(C(=O)C(C)C)=C(O)C(=O)N1c1ccc(-c2ccsc2)cc1
InChIKey: AMVDJWNLJDFPBW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 433.53, ALogP 5.55, HBA 5, HBD 1, PSA 66.84, QED 0.55
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCOCCn4cc(CN(Cc5ccccc5)Cc5cn(CCOCCOCCOc6ccc(-c7oc8ccccc8c(=O)c7OCc7cccc(C(=O)OC)c7)cc6)nn5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: JLQMCYYSZMKNHA-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1302.4
Compound (SMILES): Cc1cc(C(=O)O)c2c(C(C)C)nn(-c3ccc(Cl)cc3)c2n1
InChIKey: LRMOBVZLNQXLBI-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Displacement of fluormone pan-PPAR green from GST-tagged human PPARgamma ligand binding domain after 3 hrs by TR-FRET assay
Measurement: IC50 = 4480 nM (pChEMBL 5.349999904632568)
Descriptors: MW 329.79, ALogP 4.2, HBA 4, HBD 1, PSA 68.01, QED 0.78
Compound (SMILES): Oc1ccc(Cl)cc1-c1cnc[nH]1
InChIKey: CUHAKEYVFFILBK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 expressed in HEK293T cells assessed as reduction in kynurenine production using L-tryptophan as substrate incubated for 7 hrs by HPLC analysis
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 194.62, ALogP 2.44, HBA 2, HBD 2, PSA 48.91, QED 0.73
Compound (SMILES): O=C(Nc1ccc(C(=O)NCCOc2ccc3ccc(=O)oc3c2)cc1)Nc1ccc(Cl)c(C(F)(F)F)c1
InChIKey: DPYYRBNMSJKMCW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 3412.4 nM (pChEMBL 5.46999979019165)
Descriptors: MW 545.9, ALogP 5.92, HBA 5, HBD 3, PSA 109.67, QED 0.2
Compound (SMILES): Fc1ccc(-c2ccc3nnc(Sc4ccc5nc(NCCN6CCOCC6)sc5c4)n3n2)cc1
InChIKey: VKQVGHSFCUKNLV-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of phosphorylated MET M1250T mutant (unknown origin) pre-incubated for 30 mins before biotinylated poly(glutamate-alanine-tyrosine) peptide addition and measured after 5 mins by HTRF assay
Measurement: IC50 = 455 nM (pChEMBL 6.340000152587891)
Descriptors: MW 507.62, ALogP 4.44, HBA 10, HBD 1, PSA 80.47, QED 0.35
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)C(c1ccccc1)c1ccccc1
InChIKey: FJZJXNUBVNDBPA-NGYIUDBNSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 856.88, ALogP 4.6, HBA 11, HBD 6, PSA 268.18, QED 0.02
Compound (SMILES): O=C(Nc1cccc(-c2nc(NC(P(=O)(O)O)P(=O)(O)O)c3ccsc3n2)c1)c1ccccc1
InChIKey: QQFCQDRBVCSYKL-UHFFFAOYSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: In Vitro hGGPPS Inhibition Assay: The assay was based on a literature procedure (Kavanagh, et al. J. Biol. Chem., 2006, 281, 22004-22012) with minor modifications. All assays were run in triplicate using recombinant human GGPPS (80 ng), FPP (10 μM), IPP (8.3 μM; 3H-IPP, 40 mCi/mmoL) in a final volume of 100 μL buffer containing 50 mM Tris pH 7.7, 2 mM MgCl2, 1 mM TCEP, 5 μg/mL BSA and 0.2% (w/v) Tween 20. The enzyme and test compound were pre-incubated in the assay buffer in a volume of 80 μL at 37° C. for 10 mins. Afterwards, the substrates (FPP, IPP) were added to start the reaction, which also bring the compound, substrate, and buffer contents to the desired final concentrations as indicated above. The assay mixture was then incubated at 37° C. for 15 mins (Note: the incubation time is based from the curve determined each time a new batch of enzyme is produced). Assays were terminated by the addition of 200 μL of HCl/MeOH (1:4) and incubated for 10 min at 37° C. The mixture was then extracted with 700 μL of petroleum ether, dried through a plug of anhydrous Mg2SO4 and 300 μL of the dried ligroin phase was combined with 8 mL of scintillation cocktail. Finally, the radioactivity was counted using a Beckman Coulter LS6500 liquid scintillation counter.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 520.4, ALogP 3.66, HBA 7, HBD 6, PSA 181.97, QED 0.2
Compound (SMILES): CC1=C(CC(=O)NCc2cc(Cl)ccc2CN)C(=O)N(NCc2ccccc2)CC1
InChIKey: YWFMRWMBBNBQMO-UHFFFAOYSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition of human F9a using pefachrome F9a as substrate preincubated for 300 secs followed by substrate addition measured after 40 mins
Measurement: Ki > 29000 nM (pChEMBL 4.538000106811523)
Descriptors: MW 426.95, ALogP 3.06, HBA 4, HBD 3, PSA 87.46, QED 0.6
Compound (SMILES): N#Cc1ccc(N2CCC(Nc3cc(Nc4ccccn4)ncc3C(N)=O)CC2)nc1
InChIKey: OGJWWUCDNHVDOY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO-K1 cells after 10 mins by Rb efflux assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 414.47, ALogP 2.67, HBA 8, HBD 3, PSA 132.85, QED 0.56
Compound (SMILES): CC(=O)/C(=C\c1cccs1)C(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: YMJYNNBBJGHAJE-NTEUORMPSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 350.42, ALogP 2.01, HBA 5, HBD 2, PSA 106.33, QED 0.49
Compound (SMILES): CN1CCNC[C@H]1COc1nc(-c2cnn(C)c2)cc2nccnc12
InChIKey: KSBWPNWWWVOGJM-ZDUSSCGKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cell membranes after 2 hrs by cy3b-dofetilide-based fluorescence polarization assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 339.4, ALogP 0.71, HBA 8, HBD 1, PSA 80.99, QED 0.75
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3Cl)c3cccc(F)c32)c(F)c1
InChIKey: USQIKZSDKLRHFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 446.24, ALogP 6.14, HBA 3, HBD 1, PSA 59.3, QED 0.38
Compound (SMILES): O=c1[nH]c(CNC(CO)CO)c(I)c(=O)[nH]1
InChIKey: KHWSEDWCLNPYBR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes by HPLC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 341.11, ALogP -1.89, HBA 5, HBD 5, PSA 118.21, QED 0.4
Compound (SMILES): CN1CCNC[C@H]1CNc1nc(-c2cnn(C)c2)cc2nccnc12
InChIKey: VXSNANTYOVCQNO-ZDUSSCGKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cell membranes after 2 hrs by cy3b-dofetilide-based fluorescence polarization assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 338.42, ALogP 0.74, HBA 8, HBD 2, PSA 83.79, QED 0.73
Compound (SMILES): O=C1C=C(c2ccccc2)S(=O)(=O)N1
InChIKey: XRTSKRBKMFJBJV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibitory constant preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 209.23, ALogP 0.49, HBA 3, HBD 1, PSA 63.24, QED 0.73
Compound (SMILES): COc1cc(O)ccc1-c1cn2c(=O)n(-c3ccccc3)nc2c(N)n1
InChIKey: UVFATQJHJQXQPF-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of NECA-stimulated adenylyl cyclase activity by Glo-sensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 349.35, ALogP 1.84, HBA 8, HBD 2, PSA 107.67, QED 0.58
Compound (SMILES): COc1cc(OC)c2c(=O)cc(-c3cc(C)c(OC[C@H](O)CN4CCCCC4)c(C)c3)oc2c1
InChIKey: CSTRBRUZBLYKBT-HXUWFJFHSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to recombinant BRD4 BD2 (unknown origin) incubated for 1 hr by TR-FRET assay
Measurement: Kd = 684 nM (pChEMBL 6.170000076293945)
Descriptors: MW 467.56, ALogP 4.32, HBA 7, HBD 1, PSA 81.37, QED 0.53
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc2n1C1CC1
InChIKey: UZUCFTPPULEGQO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 368 nM (pChEMBL 6.429999828338623)
Descriptors: MW 504.59, ALogP 4.47, HBA 8, HBD 1, PSA 75, QED 0.4
Compound (SMILES): CCCCCn1nc(C(=O)NC23CC4CC(CC(C4)C2)C3)c2cccnc21
InChIKey: TZFLBZGGZTYULU-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in AtT-20 cells measured every 2 secs for 2 mins by FLIPR assay
Measurement: EC50 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 366.51, ALogP 4.32, HBA 4, HBD 1, PSA 59.81, QED 0.77
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NC(C)(C)C)cc12
InChIKey: YSFIKYDQTQWEIH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: Compound dilution series were prepared in DMSO via an approximately 3-fold serial dilution. Compound dilutions were added directly into white, low-volume assay plates (Perkin Elmer Proxiplate 384 Plus#6008280) using a Labcyte Echo in conjunction with Labcyte Access and Thermo Multidrop CombinL robotics. Compounds were then suspended in eight microliters (μL) of assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and Alexa-647-conjugated probe.The final concentration of 1× assay mixture contained 2% DMSO, 12 nM His tagged BRD4 (BDI_K57-E168) and 100 nM probe or 4 nM His tagged BRD4 (BDII_E352-M457) and 30 nM probe, and 1 nM Europium-conjugated anti-His-tag antibody, and compound concentrations in the range of: 49.02 μM-0.61 nM or 0.98 μM-0.15 nM.After a one-hour equilibration at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 519.62, ALogP 5.84, HBA 5, HBD 3, PSA 96.35, QED 0.31
Compound (SMILES): C[C@@H](C(=O)O)[C@H]1CSC(N)=N1
InChIKey: HQCCRLRYTXVTRA-QWWZWVQMSA-N
Target: Sodium- and chloride-dependent GABA transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSD5
Assay: Inhibition of human GAT2 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 174.22, ALogP 0.14, HBA 4, HBD 2, PSA 75.68, QED 0.62
Compound (SMILES): O=C(O)c1ccc(COc2ccccc2-c2ccccc2)cc1
InChIKey: PBSCWLDYPNCUHW-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Binding affinity to human RXRalpha LBD by ITC
Measurement: Kd = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 304.35, ALogP 4.63, HBA 2, HBD 1, PSA 46.53, QED 0.75
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)/C(Cc2ccc(O)c(Br)c2)=N/OC2CCCCO2)cc1
InChIKey: QCNUSTXPCIILJP-LGUFXXKBSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 expressed in Escherichia coli by stopped-flow CO2 hydration assay
Measurement: Ki = 16400 nM (pChEMBL 4.789999961853027)
Descriptors: MW 540.44, ALogP 2.6, HBA 7, HBD 3, PSA 140.31, QED 0.33
Compound (SMILES): Cc1ccc(-c2cc3ncccc3c(NC[C@H]3CCCNC3)n2)cc1
InChIKey: IWJFCANKVWBSEX-INIZCTEOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cell membranes after 2 hrs by cy3b-dofetilide-based fluorescence polarization assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 332.45, ALogP 4.02, HBA 4, HBD 2, PSA 49.84, QED 0.76
Compound (SMILES): CC(C)N1CCC(c2cnn(-c3nccc4c(=O)[nH]cnc34)c2)CC1
InChIKey: WXDMSMYTZQAHRC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 566 nM (pChEMBL 6.25)
Descriptors: MW 338.42, ALogP 2.09, HBA 6, HBD 1, PSA 79.7, QED 0.79
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)C1(C)CC1
InChIKey: OADYUDBYVXKDPZ-YFNKSVMNSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 744.75, ALogP 2.56, HBA 11, HBD 6, PSA 268.18, QED 0.04
Compound (SMILES): CC(C)(C)CNc1nccc(N2CC[C@@H](N)C2)n1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: OUXHKDXZJVBYCT-YQFADDPSSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of 5 nM [3H-pyrilamine from human H1R expressed in Sf9 cell membranes co-expressing RGS4 by competition binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 249.36, ALogP 1.47, HBA 5, HBD 2, PSA 67.07, QED 0.85
Compound (SMILES): Clc1ccc(C#Cc2nc(NC3CCCC3)c3nc[nH]c3n2)s1
InChIKey: XZDRDRRVIDEBHK-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241385 from human A2A receptor expressed in HEK293 cell membranes
Measurement: Ki = 1340 nM (pChEMBL 5.869999885559082)
Descriptors: MW 343.84, ALogP 3.82, HBA 5, HBD 2, PSA 66.49, QED 0.69
Compound (SMILES): CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@](F)(Br)[C@H]1O)Oc1ccccc1
InChIKey: ZTJBRLHJSDGEDC-JGNVGUCCSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase in HCV genotype 1b/3a chimeric replicon infected in human HuH7 replicon cells after 5 days by RT-PCR analysis
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 594.33, ALogP 1.99, HBA 10, HBD 3, PSA 158.18, QED 0.21
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1cnc(N2CCc3cc(S(=O)(=O)Nc4c(F)cc(Cl)cc4F)cc(N4CCCC4=O)c32)nc1
InChIKey: VSZRYLHBOKTNBO-UHFFFAOYSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: Affinity Biochemical interaction (RapidFire/MS assay ) EUB0000315b MGAT2
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 654.02, ALogP 5.45, HBA 8, HBD 1, PSA 113.32, QED 0.28
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)Cc1ccc(O)cc1)C(=O)N(C)[C@H](CC(=O)O)C(=O)N(C)[C@@H](Cc1ccccc1)C(N)=O
InChIKey: CPCGKBFIZZJNOY-GKSJVXRTSA-N
Target: Gastrin/cholecystokinin type B receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P32239
Assay: Agonist activity at human CCK2R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1641.97
Compound (SMILES): CN(C)C(=O)Cn1cc(-c2ccc(-c3cncc4ccccc34)cc2)cn1
InChIKey: WULUGQONDYDNKY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Affinity Phenotypic Cellular interaction: (Inhibition of pSTAT S727 in NK-92 cells) EUB0000162b CDK8
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 356.43, ALogP 3.85, HBA 4, HBD 0, PSA 51.02, QED 0.56
Compound (SMILES): Cc1c(-c2ccc3[nH]ccc3c2)ccc2c1CCNC2=O
InChIKey: CVMCCIUJSPKJJF-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 4168.69 nM (pChEMBL 5.380000114440918)
Descriptors: MW 276.34, ALogP 3.43, HBA 1, HBD 2, PSA 44.89, QED 0.7
Compound (SMILES): Cc1ccc2c(c1)C(=O)Nc1cccc(n1)-c1nncn1CCCCO2
InChIKey: VARAJTFYIRTKBZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: TR-FRET Assay: Table 1: Briefly, 20 μL aliquots of a 1.5× stock of ASK1, STK Substrate 3 and Assay Buffer were distributed in the wells of a white 384 well Optiplate, prior to addition of 0.3 μL of a 100× compound stock in DMSO, or DMSO alone in Blank and 100% Activity Controls. After a 10 minute pre-incubation, ASK1 protein kinase activity was initiated by addition of 10 μL of 300 μM ATP. After 5 hours, the kinase activity was quenched by addition of 30 μL of CisBio Kit 62ST3PEJ components: 0.5 μM of Streptavidin XL665; and 100×STK Antibody-Eu Cryptate; in Detection Buffer containing sufficient EDTA to chelate Mg2+ in the assay buffer. The plates were read after 65 minutes in an Envision Plate reader, with the following components and settings: Top Mirror, Lance Delfia Dual (662); UV Ex Filter, 320 nm (111); Emission Filter for donor, 615 nm (203); Emission Filter for Acceptor; 665 nM (205); and 100 usec delay, with 665/615 ratio output.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 349.39, ALogP 3.07, HBA 6, HBD 1, PSA 81.93, QED 0.67
Compound (SMILES): COc1ccc(COCC(O)C[SeH])cc1
InChIKey: FEWSNGJCDCXAGA-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA1 incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 44500 nM (pChEMBL 4.349999904632568)
Descriptors: MW 275.21
Compound (SMILES): Cc1cccc(-c2ncn(CC(F)F)c2-c2ccc3ncc(C(N)=O)n3c2)n1
InChIKey: IRFYJXPFDRTUSQ-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of TGFBR1 in TGFbeta-stimulated human NHLF cells assessed as reduction in SMAD2 nuclear translocation
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 382.37, ALogP 2.93, HBA 6, HBD 1, PSA 91.1, QED 0.57
Compound (SMILES): CC(=O)N1N=C(c2cccc(OS(N)(=O)=O)c2)CC1c1ccccc1Cl
InChIKey: NGGXDQCJATZIPA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 74.4 nM (pChEMBL 7.130000114440918)
Descriptors: MW 393.85, ALogP 2.62, HBA 5, HBD 1, PSA 102.06, QED 0.86
Compound (SMILES): C=CCCn1cc(-c2cc(C(=O)N3CCOCC3)c3c(c2)ncn3C)c2cc[nH]c2c1=O
InChIKey: WZSQCCTZFYLIKW-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant His-tagged BRD4 bromodomain 2 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 431.5, ALogP 2.93, HBA 6, HBD 1, PSA 85.15, QED 0.49
Compound (SMILES): COc1ccc([C@H]2c3cccc(c3O)NC(=O)/C(C)=C/C=C\[C@H](OC)[C@@H](OC(N)=O)/C(C)=C/[C@H](C)[C@@H](OC)[C@@H](OC)C[C@@H]2C)cc1
InChIKey: BCYYXUYECZFJDC-JYVZLIHVSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of fluorescent labelled-VER00051001 from N-terminal ATP-binding site of human recombinant HSP90A expressed in Escherichia coli measured after 32 hrs by fluorescence polarization assay
Measurement: IC50 = 100.7 nM (pChEMBL 7)
Descriptors: MW 636.79, ALogP 6.1, HBA 8, HBD 3, PSA 138.57, QED 0.26
Compound (SMILES): Cl.NOC(CCc1ccccc1)c1ccccc1F
InChIKey: DCWOSDQHHDKHBZ-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in human T-REx cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 49700 nM (pChEMBL 4.300000190734863)
Descriptors: MW 245.3, ALogP 3.39, HBA 2, HBD 1, PSA 35.25, QED 0.82
Compound (SMILES): CN1CC=C(c2nsnc2OCCCN2CCN(CCCCC3CCN(CC(=O)N4c5ccccc5NC(=O)c5ccccc54)CC3)CC2)CC1
InChIKey: XFGSFWFIJFNGQY-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from human muscarinic M4 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 2.57 nM (pChEMBL 8.59000015258789)
Descriptors: MW 712.97, ALogP 5.46, HBA 10, HBD 1, PSA 97.38, QED 0.23
Compound (SMILES): CCNC(=O)c1cc2c(-c3cc(C4(O)CCOCC4)ccc3Oc3c(C)cc(F)cc3C)cn(C)c(=O)c2[nH]1
InChIKey: CYDUEONTVTZMHC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of human N-terminal His6 tagged BRD4 BD1 (57 to 168) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 533.6, ALogP 4.83, HBA 6, HBD 3, PSA 105.58, QED 0.33
Compound (SMILES): Cc1nc(C2CCN(C(=O)c3ccc(OC(F)(F)F)cc3N)CC2)c2ncc(N3CCN(C)CC3)cc2n1
InChIKey: AROOGPVJRFLMEV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Affinity Biochemical interaction (TR-FRET assay (250 µM ATP)) EUB0000708a MAPK7
Measurement: IC50 > 6400 nM (pChEMBL 5.193999767303467)
Descriptors: MW 529.57, ALogP 3.59, HBA 8, HBD 1, PSA 100.71, QED 0.51
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)C(C)C)[C@@H](C)O
InChIKey: JFNLGDMELPOWTB-VLSRZGDXSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Antagonist activity at rat alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 7570 nM (pChEMBL 5.119999885559082)
Descriptors: MW 3422.84
Compound (SMILES): CCn1cncc1-c1c[nH]c2ccc(C)cc12
InChIKey: OZDZKNVFRWJEKF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human recombinant 5-HT7B receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 225.29, ALogP 3.36, HBA 2, HBD 1, PSA 33.61, QED 0.71
Compound (SMILES): Nc1nc(NC(=O)Nc2ccc(C(=O)O)cc2)nn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: NYQIKAJRNMNPOT-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 19.9 nM (pChEMBL 7.699999809265137)
Descriptors: MW 417.41, ALogP 0.84, HBA 8, HBD 5, PSA 195.32, QED 0.4
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cccnn1
InChIKey: RIMNYGJVCCUIFM-SSZFMOIBSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: FAAH Assay: All reagents were purchased from Sigma-Aldrich unless specified. Human and Rat Fatty Acid Amide Hydrolase (FAAH) genes used in assay have been described by Patricelli et al. (Biochemistry. 1998, 37(43), 15177-87). The transmembrane domain-deleted Fatty Acid Amide Hydrolase (FAAH) genes were cloned into pET15b (Novagen, #69661) (human FAAH)/pET 28a (Novagen, #69864-3) (rat FAAH gene) plasmids and expressed in E coli BL21 DE3. Chaperone protein groEL-groES in pGRO7 plasmid (Takara Bio Inc, Japan) was co-expressed with Fatty Acid Amide Hydrolase (FAAH) to improve solubility of the protein expressed in E coli. The protein was expressed and enriched as described in Mileni et al. (Proc Natl Acad Sci USA. 2008, 105(35),12820-4). Briefly, the bacterial cultures in Luria Broth (2 L) were induced with arabinose (2 mM) and Isopropyl (β-D-1-thiogalactopyranoside, IPTG (1 mM), for 20 h at room temperature. The cultures were centrifuged at 1200×g for 10 min and the cell pellet was resuspended in 100 mL buffer containing of 20 mM NaPi (pH 7.4), 100 mM NaCl, Benzonase (500u), Aprotinin (1 μg/mL) and Leupeptin (1 μg/mL). Cells were lyzed by sonication (Amp 20%, Pulse 15 s×15, on ice) and the cell debris removed by centrifugation at 5000×g for 20 min. The supernatant was enriched via ultracentrifugation at 100,000×g for 1 h and the cell pellet was resuspended in 16 mL buffer containing 20 mM NaPi (pH 7.8), 500 mM NaCl, 1% Triton X-100. The resuspended cell extract was subjected to ultra-centrifugation at 100,000×g for 1 h and the enriched supernatant was used in the in vitro assay. All protein extraction steps were carried out on ice or at 4° C.
Measurement: IC50 = 408 nM (pChEMBL 6.389999866485596)
Descriptors: MW 454.45, ALogP 5.44, HBA 5, HBD 1, PSA 77, QED 0.56
Compound (SMILES): NC(=O)C[C@H]1COc2cc(F)cc(F)c2N1C(=O)c1ccc2c(c1)NC(=O)CO2
InChIKey: FDNJKRDYTFEETA-NSHDSACASA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P22199
Assay: Antagonist activity at gal4-fused rat mineralocorticoid receptor LBD in expressed in human U2OS cells by luciferase reporter gene assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 403.34, ALogP 1.58, HBA 5, HBD 2, PSA 110.96, QED 0.81
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2cncc(-c3cccc4[nH]ccc34)c2)cc1
InChIKey: KKMZWHRTQLNOCF-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P78356
Assay: Inhibition of PI5P4Kbeta (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 363.44, ALogP 4.27, HBA 3, HBD 2, PSA 74.85, QED 0.57
Compound (SMILES): O=c1c(-c2ccccc2Cl)c2n(c(=O)n1CCCCN1CCCC(c3c[nH]c4ccccc34)C1)CCCC2
InChIKey: GXSSUFRMGVMARC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5-HT6 receptor expressed in HEK cells incubated for 1 hr by Cheng-Prusoff analysis based microbeta scintillation counting method
Measurement: Ki = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 531.1, ALogP 5.81, HBA 5, HBD 1, PSA 63.03, QED 0.31
Compound (SMILES): O=C(Nc1ccc(Oc2ccnc(NC(=O)C3CC3)c2)c(F)c1)c1cccn(-c2ccc(F)cc2)c1=O
InChIKey: UFWJGUUHERHCOL-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Displacement of fluorescein labeled ATP probe from His/GST-tagged c-Met (unknown origin) incubated for 60 mins by HTRF assay
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 502.48, ALogP 4.9, HBA 6, HBD 2, PSA 102.32, QED 0.37
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCCCCCN4CCCCCC4)cc3)cc(=O)c2c1
InChIKey: UKIGXRPAJQOYHR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 5 mins prior to substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 433.59, ALogP 6.58, HBA 4, HBD 0, PSA 42.68, QED 0.36
Compound (SMILES): CCC1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN3C(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CO)NC1=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](Cc1ccc(-c3ccccc3)cc1)C(=O)N2
InChIKey: NHPVRNNXFZLMPU-IOSLPDJESA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibition of recombinant human chymase expressed in Pichia pastoris using NleTDY-pNA as substrate by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1615.86
Compound (SMILES): COc1ccc2c(c1)c(-c1[nH]c3cccc[n+]3c1C)cn2S(=O)(=O)c1ccccc1.[Br-]
InChIKey: OWCISIJGWMSOHY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 418.5, ALogP 3.93, HBA 4, HBD 1, PSA 68.19, QED 0.45
Compound (SMILES): COC(=O)N1CCN([C@H]2CC[C@H](Nc3ncnc4ccc(C#N)cc34)CC2)CC1
InChIKey: YCFRZMCRPHNZOC-QAQDUYKDSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) in presence of 5 mM ATP by enzymatic assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 394.48, ALogP 2.61, HBA 7, HBD 1, PSA 94.38, QED 0.85
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc(-c2ccccn2)cc1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: KOSPWJNYFUWBGQ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D4 receptor stably expressed in HEK cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 1833 nM (pChEMBL 5.739999771118164)
Descriptors: MW 506.09, ALogP 6.44, HBA 4, HBD 1, PSA 54.46, QED 0.27
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C2\C(=O)N(Cc3ccccc3)c3ccc(Cl)cc32)cc1
InChIKey: MYZKXOBWXUDLLE-QQTULTPQSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 33.7 nM (pChEMBL 7.46999979019165)
Descriptors: MW 440.91, ALogP 3.35, HBA 5, HBD 2, PSA 104.86, QED 0.59
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CC1CC1CNC(=O)c1cc2ccccc2[nH]1
InChIKey: QKMCUEOKZNEZFG-VNGDJDOVSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-(R)-(+)-7-OH-DPAT from recombinant human D2L receptor expressed in HEK293 cell membranes measured after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 419.53, ALogP 2.97, HBA 5, HBD 3, PSA 96.27, QED 0.57
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)[C@H](C)CN(c2cc(C(=O)O)c4ccn(C)c4c2)C3=O)cc(C)c1Cl
InChIKey: KRPZNIACIZJAQA-JOCHJYFZSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of FITC-labeled Bak peptide binding to Bcl-2 (unknown origin) after 0.5 hrs by fluorescence polarization assay
Measurement: Ki = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 712.68, ALogP 9.01, HBA 7, HBD 1, PSA 94.52, QED 0.16
Compound (SMILES): Cl.O=C(N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1csc2ccccc12
InChIKey: OHCHVWXRKNGTQR-NWLBSPLSSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at recombinant mouse mu opioid receptor expressed in CHO cell membrane assessed as [35]-GTPgammaS binding incubated for 1.5 hrs by scintillation counting method
Measurement: EC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 502.64, ALogP 3.97, HBA 6, HBD 3, PSA 82.03, QED 0.5
Compound (SMILES): O=C(NC1CC1)c1nc2cccnn2c1-c1ccc2ncnn2c1
InChIKey: KZFDLYSKEWBCTB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Scintillation Proximity Assay (SPA): The PDE4A3, PDE4B1, PDE4C1 and PDE4D3 assays use the Scintillation Proximity Assay (SPA) technology to measure the inhibition of human recombinant PDE4A1, PDE4B3, PDE4C1, and PDE4D3 enzyme activity by compounds in vitro. The PDE4A1, PDE4B3, PDE4C1, and PDE4D3 assays are run in parallel using identical parameters, except for the concentration of enzyme (80 pM PDE4A3, 40 pM PDE4B3, 40 pM PDE4C1 and 10 pM PDE4D). The assays are performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE4A3, PDE4B1, PDE4C1, and PDE4D to convert 20% of substrate (1 μM cAMP consisting of 20 nM 3H-cAMP+980 uM cold cAMP) and a range of inhibitors. Reactions are incubated for 30 min at 25° C. The addition of 20 uL of 8 mg/ml yitrium silicate SPA beads (Perkin Elmer) stops the reaction. The plates are sealed (TopSeal, Perkin Elmer) and the beads are allowed to settle for 8 hrs, after which they are read on the Trilux Microbeta overnight.
Measurement: IC50 = 64.4 nM (pChEMBL 7.190000057220459)
Descriptors: MW 319.33, ALogP 1.33, HBA 7, HBD 1, PSA 89.48, QED 0.62
Compound (SMILES): Nc1ncnc2c1c(OCc1ccccc1)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
InChIKey: IRZWOFPUKRWUFQ-CNEMSGBDSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of ATG7 in human 293HEK cells assessed as inhibition of ATG7:ATG8 thioester formation after 8 hrs by Western blot analysis
Measurement: IC50 = 1280 nM (pChEMBL 5.889999866485596)
Descriptors: MW 452.45, ALogP -1.17, HBA 12, HBD 4, PSA 197.93, QED 0.34
Compound (SMILES): COC(=O)[C@@H]1CC(=O)N(c2ccc(S(N)(=O)=O)cc2)[C@H]1c1ccc(F)cc1
InChIKey: GOMKLKMHMLKMDT-WBVHZDCISA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 86.3 nM (pChEMBL 7.059999942779541)
Descriptors: MW 392.41, ALogP 1.74, HBA 5, HBD 1, PSA 106.77, QED 0.8
Compound (SMILES): CCOc1ccc(Cc2ccccc2)cc1CNC(=O)[C@@H](N)Cc1c(C)cc(O)cc1C.O=C(O)C(F)(F)F
InChIKey: NULXATSSMPKLTD-UQIIZPHYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Agonist activity at rat Mu-type opioid receptor expressed in rat C6 cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 1 hr by liquid scintillation counting method
Measurement: EC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 432.56, ALogP 4.18, HBA 4, HBD 3, PSA 84.58, QED 0.47
Compound (SMILES): O=C(c1cccc(Cl)c1)N1CCC(=CC#Cc2cccc(Cl)n2)CC1
InChIKey: AYGQZKNIHLPKOG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Negative allosteric modulation of human mGlu5 receptor expressed in CHO-TREx cell membranes assessed as reduction in quisqualate-induced Ca2+ mobilization incubated for 18 hrs and measured every 1.5 secs intervals for 60 secs by Fluo-4/AM dye-based fluorescence analysis
Measurement: IC50 = 287 nM (pChEMBL 6.539999961853027)
Descriptors: MW 371.27, ALogP 4.6, HBA 2, HBD 0, PSA 33.2, QED 0.54
Compound (SMILES): Cl.O=S1(=O)c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ccccc2Cl)CC1
InChIKey: RUYPKJLDKNPSBZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 507 nM (pChEMBL 6.289999961853027)
Descriptors: MW 484.07, ALogP 5.38, HBA 4, HBD 0, PSA 43.86, QED 0.4
Compound (SMILES): CCCN1C(=O)/C(=N\Nc2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: XQNYORMJZQLZGB-SILNSSARSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 47.1 nM (pChEMBL 7.329999923706055)
Descriptors: MW 358.42, ALogP 1.91, HBA 5, HBD 2, PSA 104.86, QED 0.8
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ncccc4C(F)(F)F)CC3)nc2c1
InChIKey: JGEZDSXGEXKMGW-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.46, ALogP 4.74, HBA 6, HBD 1, PSA 82.45, QED 0.45
Compound (SMILES): Nc1ncnc2c(C(=O)Nc3cccc4c3c(Br)nn4Cc3cccnc3)csc12
InChIKey: RNSPJNIKRAJKOU-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 = 2020 nM (pChEMBL 5.699999809265137)
Descriptors: MW 480.35, ALogP 4.08, HBA 8, HBD 2, PSA 111.61, QED 0.4
Compound (SMILES): Cc1cc(-c2ccccc2)cc(C(=O)NNS(=O)(=O)c2ccccc2)c1F
InChIKey: PHHZKBMVRPULAW-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Inhibition of KAT6A (unknown origin) extracted from baculovirus infected Sf9 cells using [3H]-acetyl-coA as substrate measured for 2 hrs by liquid scintillation counter analysis
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 384.43, ALogP 3.42, HBA 3, HBD 2, PSA 75.27, QED 0.66
Compound (SMILES): CC[C@H](Nc1nc(N)nc(C)c1C#N)c1nc2cccc(NCc3ccc(C(=O)NO)cc3)c2c(=O)n1-c1ccccc1
InChIKey: OUFOTOLRWBQNQU-QHCPKHFHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 575.63, ALogP 4.23, HBA 11, HBD 5, PSA 183.87, QED 0.13
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc(C(C)N5CCN(C(=O)CC(F)(F)F)CC5)ccn4)[nH]c3c2)n1
InChIKey: SYMILEXMAHCATG-UHFFFAOYSA-N
Target: IKK epsilon/TBK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of IKKepsilon/TBK1 in human MDB-MB-231 cells transduced with lentiviral vector expressing human IRF3 assessed as decrease in poly(I:C)-stimulated IRF3 phosphorylation at S385/386 residues preincubated for 1 hr followed by poly(I:C) addition and measured after 1 hr
Measurement: IC50 = 2270 nM (pChEMBL 5.639999866485596)
Descriptors: MW 514.51, ALogP 4.22, HBA 8, HBD 2, PSA 116.07, QED 0.39
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(C)CC4)cc3)[nH]c2c1=O
InChIKey: KVYZSLYRTMOOQF-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from recombinant human A3 adenosine receptor expressed in CHO cell membranes measured after 45 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 432.51, ALogP 0.43, HBA 7, HBD 2, PSA 124.16, QED 0.6