lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(Sc1nc2cnccc2n1-c1ccc(C2CC2)c2ccccc12)C(=O)O
InChIKey: NSXLFTWTIDIJIC-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsome using probe substrate measured after 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 389.48, ALogP 5.02, HBA 5, HBD 1, PSA 68.01, QED 0.49
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCN(S(N)(=O)=O)CC3)cc2)nc2ccsc12
InChIKey: JLPPMVVFVQHWGQ-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 203 nM (pChEMBL 6.690000057220459)
Descriptors: MW 561.69, ALogP 4.71, HBA 9, HBD 2, PSA 137.47, QED 0.31
Compound (SMILES): OC(Cc1ccccc1)CN1CCC(NCCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: LEPYGHSZGURSOB-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human D3 receptor expressed in HEK293 cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 691 nM (pChEMBL 6.159999847412109)
Descriptors: MW 496.67, ALogP 5.45, HBA 4, HBD 2, PSA 35.5, QED 0.35
Compound (SMILES): CCC(NC(=O)[C@H](Cc1ccc(O)c([N+](=O)[O-])c1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](N)CC(N)=O)C(N)=O
InChIKey: LKQQKKQSOSJUFO-QOWIWEFOSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Displacement of [125I-Tyr11]-SS14 from human SSTR3 expressed in HEK293-A cells incubated for 30 mins by gamma counting based competition radioligand binding assay
Measurement: IC50 = 6070 nM (pChEMBL 5.21999979019165)
Descriptors: MW 925.02, ALogP -0.06, HBA 12, HBD 12, PSA 378.67, QED 0.02
Compound (SMILES): CN1CCN(c2cc(C(=O)Nc3cc4cc(-c5cnn(C6CC6)c5)ccc4cn3)ccn2)CC1
InChIKey: KITGSDROWQMUKJ-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 425 nM (pChEMBL 6.369999885559082)
Descriptors: MW 453.55, ALogP 3.83, HBA 7, HBD 1, PSA 79.18, QED 0.49
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: DFZXNMRSOUHRAB-AJUYTZQHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]deltorphin-II from human DOR expressed in CHO cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: Ki = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 1022.22
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3NCCC4)c(Cl)cn2)C1
InChIKey: HGTYXDXGMWEQPT-UONOGXRCSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 416.91, ALogP 3.05, HBA 6, HBD 3, PSA 100.94, QED 0.71
Compound (SMILES): C[C@]1(O)CCC[C@@H]1n1c(=O)c(CC(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: GUFBYMCWKSZUBS-KKSFZXQISA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (±inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 2.04 nM (pChEMBL 8.6899995803833)
Descriptors: MW 485.56, ALogP 1.91, HBA 8, HBD 2, PSA 117.42, QED 0.64
Compound (SMILES): [O-][S+](CCNC1CCN(Cc2ccc(F)cc2)CC1)C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: FECGZFUZXKQCAY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human D3 receptor expressed in HEK293 cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 12400 nM (pChEMBL 4.909999847412109)
Descriptors: MW 486.6, ALogP 5.2, HBA 3, HBD 1, PSA 38.33, QED 0.42
Compound (SMILES): CN(C)c1ccc(CC(=O)N[C@@H]2CNC[C@H]2c2ccc(C(F)(F)F)cc2)cc1
InChIKey: XORRDVHOURHODX-RBUKOAKNSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant human CYP3A4 expressed in baculovirus infected insect cells using midazolam as substrate incubated for 30 mins in presence of NADPH-regenerating system by fluorescence based assay
Measurement: IC50 = 871 nM (pChEMBL 6.059999942779541)
Descriptors: MW 391.44, ALogP 3.19, HBA 3, HBD 2, PSA 44.37, QED 0.82
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cc(O)cc(F)c4)cc3C2C(=O)N(C)C[C@@H]2CCCN2)c1
InChIKey: DGZBUPNCYZBICZ-XYXHBKGXSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at SST2 (unknown origin)
Measurement: EC50 = 0.1259 nM (pChEMBL 9.899999618530273)
Descriptors: MW 521.04, ALogP 5.9, HBA 5, HBD 2, PSA 68.17, QED 0.44
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: JEIIPIFVEMKMLA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant CYP3A4 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 453.55, ALogP 4.5, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: WKVWXDMJXHFGCP-FJISBNMDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 455.64, ALogP 6.71, HBA 3, HBD 2, PSA 43.7, QED 0.37
Compound (SMILES): CC(C)(C)c1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: XGIJNCDMAVBREM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 958.4 nM (pChEMBL 6.019999980926514)
Descriptors: MW 454.57, ALogP 2.19, HBA 5, HBD 4, PSA 147.46, QED 0.51
Compound (SMILES): CC(C)(O)C(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)nc3CC[C@@H]12
InChIKey: AMFWGZXIWGMBRF-REDKUUPNSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 600.53, ALogP 4.79, HBA 5, HBD 2, PSA 96.36, QED 0.38
Compound (SMILES): Cl.O=C(Cc1ccc(Cl)c(Cl)c1)N1CCCC[C@H]1CN1CCCC1
InChIKey: NGVLSOWJSUUYDE-RSAXXLAASA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: PDSP Secondary Binding target: TMEM97 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 37.03 nM (pChEMBL 7.429999828338623)
Descriptors: MW 355.31, ALogP 4.01, HBA 2, HBD 0, PSA 23.55, QED 0.81
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N2Cc3ccc(O)cc3C[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: VZDNJIOWZQXYGZ-ZJSCUCBRSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 1350.68
Compound (SMILES): CCN1CCN(CCS(=O)(=O)c2ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c(OC)c2)CC1
InChIKey: GPAQVHTXRUBATF-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 637.23, ALogP 4.22, HBA 11, HBD 2, PSA 133.83, QED 0.3
Compound (SMILES): COc1ccc2nc3cc(Cl)ccc3c(Nc3ccc(C(=O)NO)cc3)c2n1
InChIKey: RLHSWYLCHQWPQD-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 394.82, ALogP 4.31, HBA 6, HBD 3, PSA 96.37, QED 0.27
Compound (SMILES): Cc1ccc2c(c1)C(=O)C(O)(O)C2=O
InChIKey: YSFDBEXXZHVVAE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 16800 nM (pChEMBL 4.78000020980835)
Descriptors: MW 192.17, ALogP 0.05, HBA 4, HBD 2, PSA 74.6, QED 0.45
Compound (SMILES): CCCCCCCCC1CCc2cc(CCC(N)(CO)CO)ccc2C1
InChIKey: SQKXCOAPPIICFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 361.57, ALogP 4.16, HBA 3, HBD 3, PSA 66.48, QED 0.49
Compound (SMILES): Cc1ncccc1C(=O)N([C@@H]1CCc2c(F)cc(Cl)cc21)[C@@H](C(N)=O)c1ccccc1
InChIKey: LKDFJGBMTHRPTF-FGZHOGPDSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Inhibition of human TRPV4 transfected in HEK293T cells assessed as reduction in RN1747-induced calcium influx measured after 60 mins by Fura-2 AM dye based fluorescence analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 437.9, ALogP 4.54, HBA 3, HBD 1, PSA 76.29, QED 0.64
Compound (SMILES): CC(C)C[C@H]1C(=O)N[C@H](C(=O)O)Cc2ccc(cc2)OCCC[C@@H]1C(=O)NO
InChIKey: PYXPFZLYNSTHAH-BBWFWOEESA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of human recombinant MMP13 using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by spectrophotometry
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 392.45, ALogP 1.75, HBA 5, HBD 4, PSA 124.96, QED 0.46
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccc(OC(F)(F)F)cc23)cc1
InChIKey: DWYXNGVQEJZWQA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 413.36, ALogP 5.15, HBA 5, HBD 3, PSA 83.48, QED 0.24
Compound (SMILES): COc1cc2c(cc1O)CCC(C)(CCNCCCCCCCCNc1c3c(nc4cc(Cl)ccc14)CCCC3)O2
InChIKey: UZGKESBGVBGSPI-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Displacement of propidium iodide from PAS region of electric eel AChE by fluorescence assay
Measurement: Kd = 2030 nM (pChEMBL 5.690000057220459)
Descriptors: MW 580.21, ALogP 8, HBA 6, HBD 3, PSA 75.64, QED 0.17
Compound (SMILES): C#C[C@]1(O)CC[C@H]2[C@@H]3CCc4cc(O)ccc4[C@@]3(C#N)CC[C@@]21C
InChIKey: WKLNGCCVBFFPGF-SXYSDOLCSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at full length human ERbeta receptor assessed as transcriptional activity incubated for 22 to 24 hrs by cell based luciferase reporter gene assay
Measurement: EC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 321.42, ALogP 3.29, HBA 3, HBD 2, PSA 64.25, QED 0.72
Compound (SMILES): CC1(C)C(=O)C=Cc2c1ccc1c2C(=O)C(=O)c2c(CO)coc2-1
InChIKey: VILXMKJHNZOYTK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate by absorbance based analysis
Measurement: IC50 = 2560 nM (pChEMBL 5.590000152587891)
Descriptors: MW 322.32, ALogP 2.69, HBA 5, HBD 1, PSA 84.58, QED 0.82
Compound (SMILES): COc1ccccc1NC(=O)NCCS(=O)(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: NUBNECLTKQKFKV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 56.8 nM (pChEMBL 7.25)
Descriptors: MW 428.49, ALogP 0.91, HBA 6, HBD 4, PSA 156.69, QED 0.49
Compound (SMILES): CC[C@@H](C(=O)Nc1ccc(Cl)cc1)N1CCC2(CC1)COc1cc(C(F)(F)F)ccc12
InChIKey: LJAQRRJZQKXEBX-IBGZPJMESA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human SKOV3 cells
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 452.9, ALogP 5.5, HBA 3, HBD 1, PSA 41.57, QED 0.67
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4)c(F)cn2)C1
InChIKey: UKQNWDWADMKKFN-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 399.47, ALogP 3.05, HBA 5, HBD 2, PSA 88.91, QED 0.83
Compound (SMILES): Nc1nccc(COc2cc(Cl)c3nc(N[C@@H]4CCCC[C@H]4O)sc3c2)c1Cl
InChIKey: JMGCDJNFHYFXDK-ZIAGYGMSSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 = 4114 nM (pChEMBL 5.389999866485596)
Descriptors: MW 439.37, ALogP 4.87, HBA 7, HBD 3, PSA 93.29, QED 0.53
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)C4CCN(C(=O)c5ccccc5)CC4)cc3c2)c1CN1CCCCC1
InChIKey: KQQQNQDIZDSYPM-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response-variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 706 nM (pChEMBL 6.150000095367432)
Descriptors: MW 536.68, ALogP 5.11, HBA 6, HBD 1, PSA 83.36, QED 0.37
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: SPR (active AKT1)
Measurement: Kd = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CCn1c(CO)nn(-c2cc3c(C(C)C)cn(-c4ccccc4C)c(=O)c3cc2F)c1=O
InChIKey: BZKHQYHQHLKJNX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: In Vitro Assay: DHODH Enzymatic Assay: The following assay is referred to herein as the DHODH Enzymatic Assay. To detect DHODH enzyme activities, dichloroindophenol (DCIP) is added as the final electron acceptor in the assay. DCIP can accept electrons from the reduced coenzyme Q generated in the assay, or from dihydroorotate (DHO) via FMN by binding presumably to the ubiquinone pocket. DCIP solutions are blue, with an intense absorbance around 600 nm, but becomes colorless upon reduction (J. Biol. Chem. (1986) 261, 11386). The assay buffer contained 50 nM HEPES, pH 7.5, 150 mM NaCl, 0.5 mM EDTA, and 0.1% Triton X-100 in MilliQ water. Substrate consisting of 20 mM DHO, 5 mM CoQ6, and 1 mM DCIP in assay buffer, initiates the reaction. The assay is run in end-point mode by quenching the reaction with the potent DHODH inhibitor brequinar. Absorbance measurements were obtained using the BMG Phera Star plate-reading spectrophotomer. Purified human DHODH was purchased from Proteros (cat. No. PR-0044). Chemicals were purchased from Sigma-Aldrich, Teknova, and Avanti Polar Lipids. Liquid handling was performed using Labcyte Echo and Formulatrix Tempest.
Measurement: IC50 = 0.463 nM (pChEMBL 9.329999923706055)
Descriptors: MW 436.49, ALogP 3.42, HBA 7, HBD 1, PSA 82.05, QED 0.52
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C
InChIKey: MREMAWQXBDPMKX-HVTMSEKVSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32301
Assay: Agonist activity at rat GLP-1R expressed in HEK293 cells assessed as stimulation of cAMP accumulation by FRET assay
Measurement: EC50 = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 5197.82
Compound (SMILES): Cc1cc(-c2ccc3c(c2)-c2nnc(Oc4cccc(OC(F)(F)F)c4)n2CCO3)ccn1
InChIKey: ZSMOTGGOUUIFRC-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 454.41, ALogP 5.4, HBA 7, HBD 0, PSA 71.29, QED 0.41
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of recombinant human HDAC10 using fluorogenic substrate by fluorescence microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): COc1nc(-c2csc(Nc3cc(C(C)(C)C)nn3CC(F)(F)F)n2)ccc1-n1cnc(C)c1
InChIKey: ULQTTXIVEXAAFE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 491.54, ALogP 5.51, HBA 9, HBD 1, PSA 82.68, QED 0.38
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(N(C)C3CN(CCCF)C3)cn2)N1CC(F)(F)F
InChIKey: LWSWCRMTCQGGDJ-GYCJOSAFSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 490.55, ALogP 4.34, HBA 5, HBD 1, PSA 51.29, QED 0.5
Compound (SMILES): COc1ccccc1OCCNCC1(F)CCN(C(=O)c2ccc(F)c(Cl)c2)CC1
InChIKey: YOAVLBDWCVGCKZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 0.302 nM (pChEMBL 9.520000457763672)
Descriptors: MW 438.9, ALogP 4.1, HBA 4, HBD 1, PSA 50.8, QED 0.63
Compound (SMILES): Cc1cc(C)cc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)c1
InChIKey: BZBHIVDNNVDCQT-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 20.7 nM (pChEMBL 7.679999828338623)
Descriptors: MW 426.52, ALogP 1.51, HBA 5, HBD 4, PSA 147.46, QED 0.53
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccnc(OC5CC5)c4)cnn3cc2OCCC(C)(C)O)cn1
InChIKey: KPXQGLYUMYUHHN-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 434.5, ALogP 3.27, HBA 9, HBD 1, PSA 99.59, QED 0.45
Compound (SMILES): Cc1cc(N[C@H]2CCc3ccc(Cl)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: MIVYUYYPBSQCPE-AWEZNQCLSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Mus musculus
UniProt: O35435
Assay: Inhibition of N-terminal His6-tagged mouse DHODH expressed in Escherichia coli BL21 using L-DHO as substrate and CoQ as co-substrate by DCIP dye based spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 377.83, ALogP 4.17, HBA 5, HBD 1, PSA 55.11, QED 0.74
Compound (SMILES): CCCCc1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: VDRAHCKGJIOZHN-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 35.9 nM (pChEMBL 7.449999809265137)
Descriptors: MW 454.57, ALogP 2.24, HBA 5, HBD 4, PSA 147.46, QED 0.43
Compound (SMILES): Oc1ccc(-n2cc(-c3ccccn3)nn2)cc1
InChIKey: FWCDFBFRXPYHIG-UHFFFAOYSA-N
Target: Macrophage migration inhibitory factor (SINGLE PROTEIN), Homo sapiens
UniProt: P14174
Assay: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 30 mins followed by substrate addition and measured for 175 secs
Measurement: Ki = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 238.25, ALogP 2.03, HBA 5, HBD 1, PSA 63.83, QED 0.74
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: RXHAROKPHMWUME-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood assessed as reduction in goat anti human IgM/human IL4-stimulated CD69 cell surface expression on peripheral B cells incubated for 18 hrs by FACS analysis
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 553.02, ALogP 5.04, HBA 6, HBD 3, PSA 122.59, QED 0.28
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(C)(C)F
InChIKey: LXPLSZAVQYCVGQ-CLYVBNDRSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 497.63, ALogP 5.11, HBA 5, HBD 2, PSA 56.42, QED 0.43
Compound (SMILES): COc1ccc(-c2ccnc3c(/N=N/c4ccc(S(N)(=O)=O)cc4)c(N)nn23)cc1
InChIKey: BMZCHLZLVYKQMW-WCWDXBQESA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 423.46, ALogP 3.05, HBA 9, HBD 2, PSA 150.32, QED 0.47
Compound (SMILES): COc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: GEXUHNGZLUQIMG-SCYNACPDSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 37.15 nM (pChEMBL 7.429999828338623)
Descriptors: MW 217.27, ALogP 2.5, HBA 3, HBD 1, PSA 48.39, QED 0.86
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: High Throughput Biochemical Assay: EGFR activity was measured using KinEASE (Cisbio), a time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay. In this assay, EGFR-catalyzes the phosphorylation of a universal Tyrosine kinase peptide substrate labeled with XL665. Europium conjugated phosphor-tyrosine specific antibody binds the resulting phosphorylated peptide. Formation of phosphorylated peptide is quantified by TR-FRET with Europium as the donor and XL665 the acceptor. The assay was performed in two main steps. The first step is the kinase reaction step and the second step is the detection step with TR-FRET reagents. In brief, test compounds 1:3 serially diluted in DMSO were delivered into Corning white, low volume, non-binding 384 well plates using the Echo 550 acoustic liquid dispenser (Labcyte®). EGFR enzyme (Human EGFR, cytoplasmic domain [669-1210] from Carna Biosciences Cat. No. 08-115) and substrates TK substrate-biotin (included in Cisbio HTRF KinEASE-TK kit Cat. No. 62TK0PEJ) were dispensed into assay plates using a Multi-Flo (Bio-Tek Instruments). The standard 10 μL reaction mixture contained 6 μM ATP (1×Km) or 12 μM ATP (2×Km), 1 μM biotinylated peptide, 0.3 nM EGFR (for 1×Km ATP) or 0.1 nM EGFR (for 2×Km ATP) in reaction buffer (10 mM MOPs, pH 7.0, 1.5% Glycerol, 0.5 mg/ml BSA, 10 mM Mg-Acetate, 1 mM DTT, 0.025% NP-40). After 60 min of incubation at room temperature, 10 μL of Stop and Detect Solution (1:400 Europium Cryptate labeled anti-phosphorylated peptide antibody solution and 125 nM strepavidin-XL665 Tracer in a 50 mM Hepes pH 7.0 detection buffer containing sufficient EDTA) was added. The plate was then further incubated for over 60 minutes at room temperature and read using an Envision 2103 Multilabeled reader (PerkinElmer) with excitation/emission/FRET emission at 340 nm/615 nm/665 nm, respectively.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-NHMULKRUSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 1117.33
Compound (SMILES): C/C=C/C(=O)Nc1ccc(-c2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1
InChIKey: FWVUYTUHMNSOTK-NSCUHMNNSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human N-terminal GST-tagged TYK2 cytoplasmic domain (833 to 1187 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 415.5, ALogP 4.24, HBA 6, HBD 2, PSA 79.38, QED 0.59
Compound (SMILES): O=C(Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1)c1cc([N+](=O)[O-])ccc1F
InChIKey: CSLQALGLKKWBBK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST tagged EGFR L858R/T790M double mutant (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 4223 nM (pChEMBL 5.369999885559082)
Descriptors: MW 598.99, ALogP 5.57, HBA 9, HBD 2, PSA 131.75, QED 0.14
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](C(=O)O)C3CCCCC3)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: COJPQLLOMWBEEN-ZCHKNENCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 282 nM (pChEMBL 6.550000190734863)
Descriptors: MW 456.58, ALogP 2.82, HBA 6, HBD 3, PSA 91.26, QED 0.63
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)NCc2ccccc2)cc1
InChIKey: GRFLMRGGHAVHMQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 65.7 nM (pChEMBL 7.179999828338623)
Descriptors: MW 412.49, ALogP 0.58, HBA 5, HBD 4, PSA 147.46, QED 0.5
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCC[C@@H]2C(=O)NO)cc1
InChIKey: FRNDBEYBKGOTNX-LLVKDONJSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 300.34, ALogP 0.35, HBA 5, HBD 2, PSA 95.94, QED 0.62
Compound (SMILES): CO[C@@H]1O[C@H](CNC(=O)c2cc(Br)c(C)n(Cc3ccc(F)cc3)c2=O)[C@H](O)[C@H](O)[C@H]1O
InChIKey: SKRSGLPHCNLKFU-BWZHCXAASA-N
Target: Lysophosphatidylserine lipase ABHD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N2K0
Assay: Inhibition of human ABHD12 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 515.33, ALogP 0.29, HBA 8, HBD 4, PSA 130.25, QED 0.44
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N2CCN(Cc3ccccc3)CC2)cc1
InChIKey: FQGOWPYBNKSIRG-SDNWHVSQSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 25600 nM (pChEMBL 4.590000152587891)
Descriptors: MW 407.51, ALogP 3.49, HBA 4, HBD 0, PSA 53.09, QED 0.69
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(-c3cnc4c(c3)[C@](C)(NCC(C)(C)F)C(=O)N4)ncnc21
InChIKey: YYXYTTPRFNUTKT-DEOSSOPVSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 475.53, ALogP 3.18, HBA 9, HBD 2, PSA 123.4, QED 0.44
Compound (SMILES): CNCC[C@H](Oc1cccc(N2CCN(C)c3nc(SC)ncc3C2=O)c1)c1cccs1
InChIKey: LRBRSWLNUGPGBK-IBGZPJMESA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: NET: Human norepinephrine transporter (NET) enriched membranes (5 μg) were incubated with 5 nM of radiolabeled [3H]-Nisoxetin in assay buffer containing 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH 7.4.NSB (non specific binding) was measured by adding 1 μM. After 60 min incubation at 4° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, 0.9% NaCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.
Measurement: Ki = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 469.64, ALogP 4.09, HBA 8, HBD 1, PSA 70.59, QED 0.39
Compound (SMILES): c1ccc2cc(-c3coc4ccc(-c5cn[nH]c5)nc34)ccc2c1
InChIKey: KLYOYEDXPDCWAL-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H422
Assay: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 311.34, ALogP 5.04, HBA 3, HBD 1, PSA 54.71, QED 0.5
Compound (SMILES): COc1ccc(-n2cc(-c3ccc4ccc(=O)oc4c3)c3cc(-c4ccc(C(=O)O)cc4)cnc32)cc1
InChIKey: CQHDXEWKDCKMHF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of PTPN6 (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 488.5, ALogP 6.17, HBA 6, HBD 1, PSA 94.56, QED 0.29
Compound (SMILES): NC(=O)c1ccccc1OCCNCC1(F)CCN(C(=O)c2ccc(F)c(Cl)c2)CC1
InChIKey: PFQWJWAFVWGWKC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 29.51 nM (pChEMBL 7.53000020980835)
Descriptors: MW 451.9, ALogP 3.19, HBA 4, HBD 2, PSA 84.66, QED 0.6
Compound (SMILES): CC(Sc1nc2cnccc2n1-c1ccc(C2CC2)c2ccccc12)C(=O)O
InChIKey: NSXLFTWTIDIJIC-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition of human URAT1 expressed in HEK293T cells assessed as reduction in [14C]uric acid uptake preincubated for 15 mins followed by [14C]uric acid addition by liquid scintillation counting method
Measurement: IC50 = 6140 nM (pChEMBL 5.210000038146973)
Descriptors: MW 389.48, ALogP 5.02, HBA 5, HBD 1, PSA 68.01, QED 0.49
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCN(S(N)(=O)=O)CC3)cc2)nc2ccsc12
InChIKey: JLPPMVVFVQHWGQ-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase assessed as inhibition of biotin-dUTP incorporation into wild type RT measured after 1 hr by ELISA
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 561.69, ALogP 4.71, HBA 9, HBD 2, PSA 137.47, QED 0.31
Compound (SMILES): OC(Cc1ccccc1)CN1CCC(NCCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: LEPYGHSZGURSOB-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human D4.4 receptor expressed in HEK293 cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 496.67, ALogP 5.45, HBA 4, HBD 2, PSA 35.5, QED 0.35