lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cccc(C(c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)N2CCOCC2)n1
InChIKey: CMOUAMAWEHZSJC-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of N-terminal 6-His-tagged wild type IDH1 (unknown origin) expressed in Escherichia coli BL21 cells using alpha-KG as substrate in presence of NADPH incubated for 40 mins by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.58, ALogP 5.11, HBA 4, HBD 1, PSA 45.59, QED 0.78
Compound (SMILES): Cc1cc(-c2ccc(C(=O)c3cc(=O)n(O)c(=O)[nH]3)cc2)ccc1F
InChIKey: XXRONWQXWLRHIN-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV1 integrase strand transfer activity using 5'-biotinylated oligonucleotide as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 340.31, ALogP 2.12, HBA 5, HBD 2, PSA 92.16, QED 0.56
Compound (SMILES): C=CC(=O)N1CCC[C@H]1COc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: ZJMZNFQDSWTHLP-FQEVSTJZSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human B cells assessed as reduction in anti-IgM/IL4-stimulated CD69 expression on B cells preincubated for 60 mins followed by anti-IgM antibody/IL4 stimulation and measured after 16 hrs by flow cytometry
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 533.58, ALogP 5, HBA 6, HBD 2, PSA 110.44, QED 0.39
Compound (SMILES): O=C1N[C@H](c2cncc(C#Cc3ccccc3)c2)[C@@H](c2ccccc2F)O1
InChIKey: RETSDKVSYUCURH-NHCUHLMSSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Agonist activity at human mGluR5A transfected in HEK293 cells assessed as induction of calcium release by FLIPR assay
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 358.37, ALogP 4.14, HBA 3, HBD 1, PSA 51.22, QED 0.7
Compound (SMILES): O=C(/C=C/c1ccc(OCCCCCCN2CCCC2)cc1)c1ccc(OCCCCCCN2CCCC2)cc1O
InChIKey: HMJSYJOCHJOOKM-HMMYKYKNSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence based assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 562.8, ALogP 7.36, HBA 6, HBD 1, PSA 62.24, QED 0.11
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCOCCOCCNC(=O)CCCCCN1/C(=C/C=C/C=C/C2=[N+](CCCCS(=O)(=O)[O-])c3ccccc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21)C(=O)N[C@@H](CC(C)C)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: BQDLAHRGAQPPJE-WJSZPSLZSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [3H] UR-MK300 from human neurotensin receptor 1 expressed in HT-29 cells incubated in dark after 30 mins by liquid scintillation counter analysis
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 1658.07
Compound (SMILES): CC(C)Nc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)cc3)sc2n1
InChIKey: XOHUFAXSTJMQRB-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 438.6, ALogP 3.08, HBA 7, HBD 4, PSA 95.31, QED 0.45
Compound (SMILES): COc1cc2c(cc1OC1CCCC1)CC(C(=O)Nc1ccccc1)N=C2c1ccccc1
InChIKey: NDHYRPVCUXDJEO-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of PDE4B in human PBMC assessed as inhibition in LPS-induced TNFalpha production preincubated for 30 mins followed by LPS stimulation for 18 hrs by TR-FRET analysis
Measurement: IC50 = 19320 nM (pChEMBL 4.710000038146973)
Descriptors: MW 440.54, ALogP 5.42, HBA 4, HBD 1, PSA 59.92, QED 0.56
Compound (SMILES): CC(C)C(=O)C1=C(O)C(=O)N(c2ccc(-c3ccsc3)cc2)C1c1ccccc1OCCO
InChIKey: FDLDOOPLMYSDGD-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 463.56, ALogP 4.91, HBA 6, HBD 2, PSA 87.07, QED 0.5
Compound (SMILES): CCCN1CCN(c2cccc3c2CN(S(=O)(=O)c2ccccc2)C3)CC1
InChIKey: FRRINSVGAXZLRR-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]raclopride from human recombinant dopamine D2 long receptor expressed in CHO-K1 cells incubated for 120 mins by scintillation counting analysis
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 385.53, ALogP 2.92, HBA 4, HBD 0, PSA 43.86, QED 0.79
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cccc(OC(F)F)c2)o1
InChIKey: JZAXAZJIYIQNAE-MRXNPFEDSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 467.47, ALogP 3.4, HBA 6, HBD 3, PSA 121.11, QED 0.13
Compound (SMILES): O=C(O)[C@H]1CNC[C@@H](CN/N=C/c2ccc(-c3cc(C(F)(F)F)cc(C(F)(F)F)c3)o2)C1
InChIKey: ZNIIBSXZJZZIGX-BQSCGJQXSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30531
Assay: Non-competitive inhibition of human GAT1 expressed in COS cells assessed as reduction in [2H6]GABA uptake by measuring [2H6]GABA Kd(app) at 10 uM preincubated for 25 mins followed by [2H6]GABA addition and measured after 4 mins by liquid scintillation counting method (Rvb = 28.3 +/- 1.5 nM)
Measurement: Kd = 154.2 nM (pChEMBL 6.809999942779541)
Descriptors: MW 463.38, ALogP 4.22, HBA 5, HBD 3, PSA 86.86, QED 0.34
Compound (SMILES): COc1ccc2nc(NC(=O)Cc3ccc(-c4ccncc4)cc3)sc2c1
InChIKey: IVXHZSZBXWENCY-UHFFFAOYSA-N
Target: Protein Wnt-3a (SINGLE PROTEIN), Homo sapiens
UniProt: P56704
Assay: Wnt-Luc Reporter Assay: Human embryonic kidney 293 cells (obtained from American Type Culture Collection, ATCC, Manassas, Va.) are cultured in DMEM medium (Gibco/Invitrogen, Carlsbad, Calif.) supplemented with 10% FBS (Gibco/Invitrogen, Carlsbad, Calif.), 50 unit/mL penicillin and 50 μg/mL of streptomycin (Gibco/Invitrogen, Carlsbad, Calif.) at 37° C. with 5% CO2 in air atmosphere. 293 cells in a 10 cm dish are co-transfected with 8 μg of STF-reporter plasmid containing a luciferase gene driven by Wnt-responsive elements and 2 μg of pcDNA3.1-Neo (Gibco/Invitrogen, Carlsbad, Calif.) with 30 μL of FuGENE6 (Roche Diagnostics, Indianapolis, Ind.) following the manufacturer's protocol. Stable cell lines (293 Wnt-Luc) were selected with 400 μg/mL of G418 (Gibco/Invitrogen, Carlsbad, Calif.). The 293 Wnt-Luc cells and L-cell Wnt3a cells (obtained from American Type Culture Collection, ATCC, Manassas, Va.) are trypsinized and co-cultured into a 384-well plate with DMEM medium supplemented with 2% FBS, and treated with different concentrations of a compound of the invention. After 24 hours, the firefly luciferase activities are assayed with the Bright-Glo Luciferase Assay System (Promega, Madison, Wis.). The IC50 is measured when the effect of the compound reduces the luminescence signal by 50%.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 375.45, ALogP 4.55, HBA 5, HBD 1, PSA 64.11, QED 0.56
Compound (SMILES): O=C(Cc1ccccc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: YEBWNEBTTYUFMD-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 expressed in T-REx-293 cells assessed as reduction in kynurenine level measured after 16 hrs
Measurement: EC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 401.51, ALogP 3.69, HBA 4, HBD 1, PSA 58.36, QED 0.71
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(F)c(Oc2ccc(Cl)c(Cl)c2)cc1F
InChIKey: KASGDBJYKOICKB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in HEK293 cells after 45 mins by scintillation counting analysis
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 396.2, ALogP 3.75, HBA 4, HBD 1, PSA 72.47, QED 0.85
Compound (SMILES): O=C(Nc1nc2ccc(Sc3nnc4ccc(-c5ccc(F)cc5)nn34)cc2s1)OCCN1CCOCC1
InChIKey: DTPZUUXRZNQTOC-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of wild type phosphorylated MET (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 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 551.63, ALogP 4.57, HBA 11, HBD 1, PSA 106.77, QED 0.31
Compound (SMILES): CN(C(=O)c1cn2cc(-c3cnn(C)c3)ccc2n1)[C@@H]1CCN(C#N)C1
InChIKey: WJFKNKFBAOIBMX-OAHLLOKOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 349.4, ALogP 1.36, HBA 7, HBD 0, PSA 82.46, QED 0.67
Compound (SMILES): CC1(C)CC[C@]2(C(=O)OCCCCO[N+](=O)[O-])CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)CC[C@H](O)[C@@](C)(CO)[C@@H]5CC[C@]43C)[C@@H]2C1
InChIKey: LNAWOBZZQOBUHP-WZMLTRNISA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of C-terminal His-tagged/ N-terminal GST-tagged recombinant human EGFR L858R/T790M/C797S mutant (668 to 1210 residues) expressed in a Baculovirus infected Sf9 cell expression system using poly-EY as substrate incubated for 30 mins by ADP-Glo kinase assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 589.81, ALogP 6.65, HBA 7, HBD 2, PSA 119.13, QED 0.11
Compound (SMILES): CC(C)(C)n1c(=O)cc(-c2cccs2)[s+]1[O-]
InChIKey: DFAQSRKACBMKQG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibitory constant preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 48.6 nM (pChEMBL 7.309999942779541)
Descriptors: MW 255.36, ALogP 3.06, HBA 4, HBD 0, PSA 45.06, QED 0.74
Compound (SMILES): COc1ccc(-c2cc(N(Cc3ccccn3)Cc3ccccn3)ncn2)c(F)c1
InChIKey: TZRMSEJLPYCPEI-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Inhibition of human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as decrease in ACh-induced channel currents at -60 mV holding potential by two electrode voltage clamp assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 401.45, ALogP 4.29, HBA 6, HBD 0, PSA 64.03, QED 0.46
Compound (SMILES): Cc1ccc(CNC(=O)c2csc(CCNCc3nc4ccccc4[nH]3)n2)nn1
InChIKey: XTFFCEJAOTYNBL-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 407.5, ALogP 2.38, HBA 7, HBD 3, PSA 108.48, QED 0.39
Compound (SMILES): C[C@@H]1CC2(CCN(c3nc(N)c(Sc4cccnc4C(F)(F)F)c(=O)n3C)CC2)[C@H](N)[C@H]1F
InChIKey: UFFOHMITCZLLOC-OSAQELSMSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of human 6His-tagged SHP2 (1 to 525 residues) expressed in Escherichia coli BL21 Star (DE3) using DiFMUP as surrogate substrate as preincubated for 30 to 60 mins followed by substrate addition and measured after 30 mins bpV-based fluorescence assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 486.54, ALogP 3.22, HBA 8, HBD 2, PSA 103.06, QED 0.64
Compound (SMILES): N=C(N)NCCC[C@H](N)C(=O)NCCCCC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ONIJRTOENNPBIQ-AQUVTFJZSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from human muscarinic M3 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 562.72, ALogP 2.51, HBA 6, HBD 6, PSA 169.67, QED 0.13
Compound (SMILES): COc1ccc2c(C(=O)Nc3ccc(NC(=O)c4nn(C5CCN(C(=O)NC(C)(C)C)CC5)c5ccc(F)cc45)cc3Cl)cnn2c1
InChIKey: QRHLGEHZPDSLFJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ZAP-70 (SINGLE PROTEIN), Homo sapiens
UniProt: P43403
Assay: Effect on ZAP70 phosphorylation in human Jurkat cells pre-incubated for 30 mins followed by anti-CD3/CD28 stimulation measured after 10 mins
Measurement: EC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 661.14, ALogP 6.13, HBA 8, HBD 3, PSA 134.89, QED 0.2
Compound (SMILES): CN(C)CCCNc1nc(/C=C/c2ccc(F)cc2)nc2ccc(Cl)cc12
InChIKey: TXEPPTZQOZBMOB-IZZDOVSWSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 D835Y (unknown origin) using TAMRA-Src-tide as substrate measured after 1 hr in presence of ATP at its Km concentration by IMAP-FP assay
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 384.89, ALogP 4.96, HBA 4, HBD 1, PSA 41.05, QED 0.58
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4ccc(-c5cccc(F)c5)nn34)cc2s1
InChIKey: FYGIZDILNJTZSB-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Binding affinity to MET (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 550.65, ALogP 4.15, HBA 10, HBD 2, PSA 109.57, QED 0.31
Compound (SMILES): C#Cc1ccc2c(c1)C(c1ccccc1F)=N[C@H](C)c1c(C(=O)N(C)C)ncn1-2
InChIKey: LNPOWXXHIUMIKI-CQSZACIVSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P34903
Assay: Binding affinity to GABA-A alpha3 (unknown origin)
Measurement: Ki = 63000 nM (pChEMBL 4.199999809265137)
Descriptors: MW 386.43, ALogP 3.61, HBA 4, HBD 0, PSA 50.49, QED 0.63
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4cc(F)ccc42)CSCC3)cc1
InChIKey: LOFPHNPTVBYXBB-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human HDAC4 using fluorogenic HDAC substrate
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 356.42, ALogP 3.74, HBA 4, HBD 2, PSA 54.26, QED 0.56
Compound (SMILES): O=c1cc(NCCCN2CCN(c3nc(F)cc4ccccc34)CC2)c2ccccc2o1
InChIKey: FUEFNIKXLZAKGZ-UHFFFAOYSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0AES4
Assay: Inhibition of Escherichia coli ATCC 25922 DNA gyrase A assessed as reduction in enzyme-mediated supercoiling of relaxed pBR322 DNA by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 432.5, ALogP 4.1, HBA 6, HBD 1, PSA 61.61, QED 0.28
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2nc(Nc3ccc(Cl)cc3)nc(N3CCOCC3)n2)cc1
InChIKey: PKDJLTCAEOAICS-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 870.9 nM (pChEMBL 6.059999942779541)
Descriptors: MW 504.96, ALogP 2.4, HBA 9, HBD 4, PSA 164.46, QED 0.39
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)c(F)c3F)sc2n1
InChIKey: HKHBEUOBIAVTFZ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 431.51, ALogP 2.85, HBA 6, HBD 3, PSA 83.28, QED 0.58
Compound (SMILES): CCCCCc1ccc(C(=O)N(Cc2ccc(-c3ccc(Cl)c(Cl)c3)o2)C2CCN(CCC(C)C)CC2)cc1
InChIKey: NYVBCXDVWVZUQX-UHFFFAOYSA-N
Target: Plasmepsin 4 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q17SB2
Assay: Inhibition of recombinant Plasmodium falciparum Plasmepsin 4
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 569.62, ALogP 9.14, HBA 3, HBD 0, PSA 36.69, QED 0.2
Compound (SMILES): CC(C)(C)Cc1cc(-c2onc([C@@H](CCC(=O)[O-])CC(=O)Nc3ccc(Cl)cc3Cl)c2C2CC2)no1.[Na+]
InChIKey: YEQSGBJZMBCONP-RSAXXLAASA-M
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Inhibition of GAL4-fused human PPARdelta transcriptional activity expressed in CHOK1 cells after 2 days by luciferase reporter gene assay
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 534.44, ALogP 7.08, HBA 6, HBD 2, PSA 118.46, QED 0.29
Compound (SMILES): CCOS(=O)(=O)/C=C/c1ccc(O[C@@H]2CN(C(=O)C(=O)Nc3ccccc3)C[C@H]2Oc2ccc(/C=C/S(=O)(=O)OCC)cc2)cc1
InChIKey: PGMXAQKGYYWMFS-VTZWOUEESA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) using pNPP as substrate after 30 mins
Measurement: IC50 = 2520 nM (pChEMBL 5.599999904632568)
Descriptors: MW 670.76, ALogP 4.04, HBA 10, HBD 1, PSA 154.61, QED 0.21
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC4CCOCC4)c4ncnc(N)c34)ccc2c1
InChIKey: XQDXYVGJQQZZRG-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 403.49, ALogP 4.05, HBA 7, HBD 1, PSA 88.08, QED 0.54
Compound (SMILES): CNC[C@H]1C[C@]1(F)c1ccccc1.Cl
InChIKey: NJAYXMBERKCZQC-DHXVBOOMSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant human 5HT2A receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 154.88 nM (pChEMBL 6.809999942779541)
Descriptors: MW 179.24, ALogP 2.09, HBA 1, HBD 1, PSA 12.03, QED 0.75
Compound (SMILES): CC(C)C[C@H](NC(=O)OC1CCN(S(=O)(=O)c2ccccc2F)CC1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1.O=C(O)C(F)(F)F
InChIKey: HZZOJHGDYQIGGL-UKOKCHKQSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of recombinant human N-terminal met-His6-tagged matriptase catalytic domain (Gly596 to Val855 residues) expressed in Escherichia coli using Boc-QAR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 689.84, ALogP 3.36, HBA 9, HBD 5, PSA 196.67, QED 0.07
Compound (SMILES): COc1ccc(-c2nc(N)c3nc(-c4ccccc4)sc3n2)cc1
InChIKey: PVUAHOZQHJZVSR-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cells after 3 hrs by scintillation counting method
Measurement: Ki = 115.3 nM (pChEMBL 6.940000057220459)
Descriptors: MW 334.4, ALogP 4.01, HBA 6, HBD 1, PSA 73.92, QED 0.61
Compound (SMILES): CCOc1cccc2cc(-c3cc(OC)c(OC)c(OC)c3)c(=O)oc12
InChIKey: NRVCXNQZPYRPDB-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine receptor A3 expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 9050 nM (pChEMBL 5.039999961853027)
Descriptors: MW 356.37, ALogP 3.88, HBA 6, HBD 0, PSA 67.13, QED 0.62
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2cccc(Br)c2)n(C)c1=O
InChIKey: GDXNESQVHGSDFC-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB603 from recombinant human adenosine A2b receptor expressed in HEK293 cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 404.27, ALogP 1.61, HBA 7, HBD 0, PSA 65.06, QED 0.65
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccccc1C(N)=O
InChIKey: FFYLSLMDLCQSRS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 JH1 domain (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 380.38, ALogP 2.56, HBA 6, HBD 4, PSA 122.03, QED 0.52
Compound (SMILES): COc1ccc2c(=O)n(CCc3ccccc3)c(=O)n(Cc3ccc(C(=O)NO)cc3)c2c1
InChIKey: SQBBNABXOTUYRL-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human full-length recombinant HDAC8 expressed in baculovirus infected Sf9 insect cells using fluorogenic peptide RHKAcKAc as substrate after 2 hrs
Measurement: IC50 = 731 nM (pChEMBL 6.139999866485596)
Descriptors: MW 445.48, ALogP 2.58, HBA 7, HBD 2, PSA 102.56, QED 0.34
Compound (SMILES): CCC(=O)Nc1nc(C)c(-c2cn(S(=O)(=O)c3ccccc3)c3ccc(F)cc23)[nH]1
InChIKey: TUEMKIYKYXEZDB-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 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 426.47, ALogP 4.06, HBA 5, HBD 2, PSA 96.85, QED 0.5
Compound (SMILES): O=C(CO)N[C@@H](CC(=O)N1CCn2c(nnc2C(F)(F)F)C1)Cc1cc(F)c(F)cc1F
InChIKey: GCRVRICKJRRVEG-SNVBAGLBSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human DPP-4 using Ala-Pro-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 5 to 10 mins by fluorescence assay
Measurement: IC50 = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 465.35, ALogP 1.17, HBA 6, HBD 2, PSA 100.35, QED 0.49
Compound (SMILES): CC(C)(C#N)CNC(=O)Cc1nc2cnc3[nH]ccc3c2n1[C@H]1CC[C@H](CC#N)CC1
InChIKey: CRBPNYKHFXDNRW-WKILWMFISA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2/JAK2 in human PBMC assessed as reduction in GM-CSF-induced STAT5 phosphorylation pre-incubated for 30 mins before GM-CSF stimulation for 30 mins AlphaLISAassay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 417.52, ALogP 3.77, HBA 6, HBD 2, PSA 123.18, QED 0.63
Compound (SMILES): NS(=O)(=O)c1ccc(OP(=O)(Sc2ccccc2)c2ccccc2)cc1
InChIKey: KTMXZVZXSJIZEX-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 2633 nM (pChEMBL 5.579999923706055)
Descriptors: MW 405.44, ALogP 4.02, HBA 5, HBD 1, PSA 86.46, QED 0.63
Compound (SMILES): CSCC[C@H](NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(N)=O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O
InChIKey: YUUIEAQTTXVRFZ-BIRWCAQUSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 3726.38
Compound (SMILES): O=C(Cc1ccccc1[N+](=O)[O-])Nc1ccc(-c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2F)cc1
InChIKey: MNVXADPCMINSEC-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human N-terminal His6-tagged RORgamma (262 to 507 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition of biotinylated co-activator SRC1-4 peptide recruitment by alphascreen assay
Measurement: IC50 = 3460 nM (pChEMBL 5.460000038146973)
Descriptors: MW 516.37, ALogP 5.89, HBA 4, HBD 2, PSA 92.47, QED 0.24
Compound (SMILES): C[C@@H]1CCCOc2ccccc2C(=O)Nc2cccc(n2)-c2nncn21
InChIKey: LZTAURWQYWWPLU-CYBMUJFWSA-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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 349.39, ALogP 3.33, HBA 6, HBD 1, PSA 81.93, QED 0.67
Compound (SMILES): O=C(NCc1ncc(C(F)(F)F)cc1Cl)c1ccc2c(c1)C1(CCS(=O)(=O)CC1)[C@H](C1CC1)N2S(=O)(=O)c1ccc(F)cc1
InChIKey: PZGSYNNVPNLHQG-SANMLTNESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells assessed as reduction in channel inward tail current by whole cell voltage clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 672.12, ALogP 5.26, HBA 6, HBD 1, PSA 113.51, QED 0.36
Compound (SMILES): Cc1cc2cc(n1)-c1cnn(C)c1OCCC[C@@H](C)CN1/C(=N/C2=O)Nc2ccc(CN3CCN(C)CC3)cc21
InChIKey: AIQBYZOTCIQTGW-HXUWFJFHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 542.69, ALogP 3.77, HBA 9, HBD 1, PSA 91.12, QED 0.52
Compound (SMILES): C(=N/C1CCN(Cc2ccccc2)CC1)\c1ccccc1
InChIKey: VVQPLYAHXAZPHF-HMMYKYKNSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 using as 7-Methoxycoumarin-4-acetyl-[Asn670, Leu671]-Amyloid beta/A4 precursor protein 770 fragment 667-676-(2,4-dinitrophenyl) Lys-Arg-Arg amide trifluoroacetate salt as substrate incubated for 2 hrs by FRET based florescence assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 278.4, ALogP 3.77, HBA 2, HBD 0, PSA 15.6, QED 0.78
Compound (SMILES): CO[C@H]1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3nc(N)n[nH]3)CC2)C1
InChIKey: CWVKUWZSIMMEOV-IRXDYDNUSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D7Q1
Assay: Inhibition of full-length C-terminal his-tagged mouse CHIT1 expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N\"-triacetylchitotrioside as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 345 nM (pChEMBL 6.460000038146973)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.81
Compound (SMILES): C[C@H]1CCN(S(=O)(=O)c2cc(NC(=O)Cn3nnc4c3CCN(CC(F)(F)F)C4)ccc2Br)C1
InChIKey: UKUONIURRUCQRP-ZDUSSCGKSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647-labeled ligand from BRD4 BD1 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 565.42, ALogP 2.63, HBA 7, HBD 1, PSA 100.43, QED 0.58
Compound (SMILES): CC(=O)Oc1c(C(C)C)cc2c(c1OC(C)=O)-c1cccc3c1[C@@H](C2)N(C)CC3
InChIKey: KFEHEEITVOEJOF-HXUWFJFHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at C-terminal RLuc8-fused D2 long receptor (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 393.48, ALogP 4.41, HBA 5, HBD 0, PSA 55.84, QED 0.57
Compound (SMILES): Cc1cc(-c2cnc3ccn(CC4CCC4)c3c2)ccc1F
InChIKey: MTXPFYDPXWYSJL-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 294.37, ALogP 4.95, HBA 2, HBD 0, PSA 17.82, QED 0.67
Compound (SMILES): Cc1ccc(NC(=O)N[C@@H](Cc2cc(F)cc(F)c2)C(=O)N[C@@H]2C(=O)N3CCC[C@H]3C(=O)N3CCCC[C@H]3C(=O)N[C@@H](C)C(=O)N3C[C@@H](C)C[C@H]3C(=O)O[C@H]2C)cc1
InChIKey: YYEGAPUPWRGEKG-PWUUNCOOSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Activation of Staphylococcus aureus ClpP using BODIPY-FL-casein as substrate incubated for 30 mins by Enz-Check protease assay
Measurement: EC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 807.9, ALogP 2.55, HBA 8, HBD 4, PSA 186.56, QED 0.32
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nnc(-c3nnc(SCC(=O)c4ccc(F)cc4)[nH]3)c2-c2ccccc2)cc1
InChIKey: HBLHNVJAWVVDJO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as reduction in CO2 hydration incubated for 1 hr by phenol red staining-based stopped flow assay
Measurement: Ki = 27.3 nM (pChEMBL 7.559999942779541)
Descriptors: MW 535.59, ALogP 3.48, HBA 9, HBD 2, PSA 149.51, QED 0.23
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cnc(N)nc3)c(Oc3cnc(N)s3)cc2Br)C1=O
InChIKey: YIXYPDNYHSMDJK-BNNQUZSASA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with mock Sendai virus and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 535.41, ALogP 3.9, HBA 11, HBD 2, PSA 146.55, QED 0.45
Compound (SMILES): O=C(Nc1ccc(Oc2ccc(F)cc2)cc1)N1CCc2ncccc2[C@@H]1c1ccc(Cl)cc1
InChIKey: FMQWOAKTQPLQBR-SANMLTNESA-N
Target: Lutropin-choriogonadotropic hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P22888
Assay: Antagonist activity at human luteinizing hormone receptor assessed as reduction in agonist-induced cAMP production preincubated for 20 mins followed by agonist solution addition after 60 mins by cell based TR-FRET assay
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 473.94, ALogP 6.85, HBA 3, HBD 1, PSA 54.46, QED 0.35
Compound (SMILES): CC(C)n1nc(-c2ccc3oc(N)nc3c2)c2c(F)nc(N)nc21
InChIKey: XYFXUNWLLFSAGS-UHFFFAOYSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC1 in human A431 cells assessed as S6RP phosphorylation incubated for 3 hrs by HTRF assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 327.32, ALogP 2.52, HBA 8, HBD 2, PSA 121.67, QED 0.54
Compound (SMILES): O=C(c1ccc(-c2cccc(NS(=O)(=O)c3ccccc3)c2)s1)c1c(Cl)ccc(O)c1F
InChIKey: FFPPYOWUSBRLMV-UHFFFAOYSA-N
Target: Estradiol 17-beta-dehydrogenase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P51658
Assay: Inhibition of mouse liver homogenate 17beta-HSD2 using [3H]-E2 as substrate in presence of NAD+ by radio-HPLC analysis
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 487.96, ALogP 5.95, HBA 5, HBD 2, PSA 83.47, QED 0.33
Compound (SMILES): O=C(c1cc2ccccc2[nH]1)N1CCN(CCOc2cccnc2)CC1
InChIKey: WJOFBCYZALIRKI-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: D3 Radioligand Binding Assay: Compounds were tested for their ability to compete with the orthosteric radioligand [3H]methylspiperone for binding to the D3 DAR using stable HEK cell lines expressing the D3 DAR (Codex Biosciences, Gaithersburg, Md., Catalogue no. CB-80300-206) as described in the detailed protocol below presented in Table 5. Cells were cultured in Dulbecco's modified Eagle's Medium (Corning, catalogue no. 10-013) containing 10% FBS, 1,000 units/mL Penicillin, 1,000 mg/mL Streptomycin, 100 mM sodium pyruvate, 1 μg/mL Gentamicin, and 250 mg/mL G418. All cells were maintained at 37° C. in 500 CO2 and 90% humidity. For radioligand binding assays cells were removed mechanically using calcium-free Earle's balanced salt solution (EBSS). Intact cells were collected by centrifugation and then lysed with 5 mM Tris-HCl and 5 mM MgCl2 at pH 7.4. Homogenates were centrifuged at 30,000×g for 30 minutes. The membranes were re-suspended in EBSS (US Biological, catalogue no. E0249-05) pH 7.4 to a concentration of 16 μg/mL. For competition binding studies, membrane preparations were incubated for 90 minutes at room temperature with various concentrations of compound and a single concentration of [3H]methylspiperone (Perkin Elmer, NET856) in a reaction volume of 250 μL. Non-specific binding was determined in the presence of 4 μM (+)-butaclamol (Sigma-Aldrich, catalogue no. D033). Bound ligand was separated from unbound by filtration through GF/C filters using a PerkinElmer cell harvester and quantified on a Top-count (PerkinElmer). Ki values were determined using Cheng-Prusoff equation from observed IC50 values and ligand Kd values from separate saturation experiments.
Measurement: EC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 350.42, ALogP 2.4, HBA 4, HBD 1, PSA 61.46, QED 0.77
Compound (SMILES): CN1C(=O)C(O)(CC(=O)c2ccc3ccccc3c2)c2ccccc21
InChIKey: SDEIDCCPKCHFSQ-UHFFFAOYSA-N
Target: Testis-specific chromodomain protein Y 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F8
Assay: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis
Measurement: Kd = 28900 nM (pChEMBL 4.539999961853027)
Descriptors: MW 331.37, ALogP 3.28, HBA 3, HBD 1, PSA 57.61, QED 0.75
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)c(F)c(C(=O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: NZZQNOHKPCQKKC-IEBWSBKVSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 535.57, ALogP 3.81, HBA 7, HBD 4, PSA 158.41, QED 0.08
Compound (SMILES): O=c1cc(NCCc2ccc(Cl)cc2)[nH]c(=O)[nH]1
InChIKey: JSUODDTVALGQAK-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Agonist activity at human GPR84 expressed in CHO-K1 cells assessed as reduction in forskolin-stimulated cAMP production incubated for 30 mins by luminescence assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 265.7, ALogP 1.37, HBA 3, HBD 3, PSA 77.75, QED 0.78
Compound (SMILES): O=C(/C=C/c1ccc(OCCCN2CCC(Cc3ccccc3)CC2)cc1)c1ccc(OCCCN2CCC(Cc3ccccc3)CC2)cc1O
InChIKey: IFFCYYXMNBDYSH-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 = 26100 nM (pChEMBL 4.579999923706055)
Descriptors: MW 686.94, ALogP 8.74, HBA 6, HBD 1, PSA 62.24, QED 0.07
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CCN(S(=O)(=O)CCCN3CCOCC3)CC2)n1
InChIKey: VWWBBXCQBUKGMW-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal p110alpha/p85alpha expressed in baculovirus infected Sf9 insect cells using PIP2 as substrate by HTRF assay
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 637.71, ALogP 1.17, HBA 13, HBD 0, PSA 131.28, QED 0.32
Compound (SMILES): COc1ccc2cnn(-c3ccc(S(N)(=O)=O)cc3)c(=O)c2c1OC
InChIKey: FOQCIXFYYOJQMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic CA 2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 361.38, ALogP 1.05, HBA 7, HBD 1, PSA 113.51, QED 0.74
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCC5(CNCCO5)C4)cc3)sc2n1
InChIKey: YFNCJZDINCZFFH-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 451.6, ALogP 2.73, HBA 7, HBD 3, PSA 92.51, QED 0.55
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cn[nH]c1
InChIKey: VFHRALAVCKZLHR-GDNBJRDFSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 442.44, ALogP 5.37, HBA 4, HBD 2, PSA 79.9, QED 0.56
Compound (SMILES): O=C(Nc1ccc(OS(=O)(=O)c2ccc(F)cc2)cc1)C1CCCC1
InChIKey: IPTALSQODYZAMP-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14638
Assay: Inhibition of human NPP3 expressed in African green monkey COS7 cell membranes pre-incubated for 10 mins before pNP-TMP substrate addition and further incubated for 15 mins by colorimetric method
Measurement: IC50 = 1014 nM (pChEMBL 5.989999771118164)
Descriptors: MW 363.41, ALogP 3.72, HBA 4, HBD 1, PSA 72.47, QED 0.82
Compound (SMILES): CCn1ncc2c(NC3CCCCC3)c(C(=O)NCCNc3c4c(nc5ccccc35)CCCC4)cnc21
InChIKey: SBWPXDUGJRKADY-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of recombinant human PDE4D2 catalytic domain (86 to 413 residues) expressed in Escherichia coli BL21 codonplus cells using [3H]cAMP as substrate preincubated for 15 mins followed by substrate addition by liquid scintillation counting method
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 511.67, ALogP 5.46, HBA 7, HBD 3, PSA 96.76, QED 0.27
Compound (SMILES): Nc1nc2[nH]c(CCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c3)cc2c(=O)[nH]1
InChIKey: VEKHZPVGFDPVJG-HNNXBMFYSA-N
Target: Folate receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P14207
Assay: Binding affinity to human FRbeta expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell growth after 96 hrs by Cell-Titer Blue assay
Measurement: IC50 = 3.87 nM (pChEMBL 8.40999984741211)
Descriptors: MW 459.43, ALogP 1.2, HBA 6, HBD 6, PSA 191.26, QED 0.26
Compound (SMILES): Clc1ccc(-c2nc(N3CCCCC3)c3nc[nH]c3n2)cc1
InChIKey: DGZWSPSJWMAWBF-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]NECA from human A3 receptor expressed in HeLa-A3 cells incubated for 180 mins by scintillation counting method based radioligand competitive binding assay
Measurement: Ki = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 313.79, ALogP 3.66, HBA 4, HBD 1, PSA 57.7, QED 0.78
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell Assay: Inhibition of RSK phosphorylation (pRSK A375SM)
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): CC[C@@H](/C=C/[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C
InChIKey: JZVFJDZBLUFKCA-INYURWPISA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX1
Measurement: IC50 = 16200 nM (pChEMBL 4.789999961853027)
Descriptors: MW 412.7, ALogP 7.8, HBA 1, HBD 1, PSA 20.23, QED 0.46