lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)C(=O)c1ccc(N(Cc2ccc(C#N)cc2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: FLCLKDRMVXBLHR-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of PDHK1 (unknown origin) by radiometric biochemical kinase assay
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 415.45, ALogP 3.52, HBA 5, HBD 2, PSA 104.87, QED 0.66
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: YNTHWMGRAUMNFY-KOQODJNWSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 756.9, ALogP 1.27, HBA 8, HBD 7, PSA 214.72, QED 0.17
Compound (SMILES): Cc1n[nH]cc1-c1cc2nc([C@@H]3CCC(C)(C)N3)[nH]c(=O)c2s1
InChIKey: JBGVICNHTUXKQA-JTQLQIEISA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition of N-terminal GST-tagged human ROCK1 catalytic domain (1 to 477 residues) expressed in baculovirus expression system using biotin-STK-substrate 2 as substrate preincubated with enzyme for 5 mins followed by ATP addition and measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 329.43, ALogP 2.89, HBA 5, HBD 3, PSA 86.46, QED 0.67
Compound (SMILES): O=C(O)C1CCCN(CC/C=C\C(c2ccccc2)(c2ccccc2)c2ccccc2)C1
InChIKey: OOVKPEDIGJRFSH-JMIUGGIZSA-N
Target: GABA transporter 3 (SINGLE PROTEIN), Mus musculus
UniProt: P31649
Assay: Inhibition of mouse GAT2 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 10 mins by microbeta liquid scintillation counting method
Measurement: IC50 = 54954.09 nM (pChEMBL 4.260000228881836)
Descriptors: MW 425.57, ALogP 5.76, HBA 2, HBD 1, PSA 40.54, QED 0.37
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: ASNDURJGUUDPHG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1/CyclinB1 (unknown origin) using histone H1 (GGGPATPKKAKKL) as substrate incubated for 80 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 2610 nM (pChEMBL 5.579999923706055)
Descriptors: MW 304.38, ALogP 1.75, HBA 5, HBD 2, PSA 97.97, QED 0.9
Compound (SMILES): CNC(=O)Cc1ccc(Nc2cc(-c3cccc(Cl)c3)nc3c2CCC3)cc1
InChIKey: NKNXGHSIYQVARV-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Kinetic Assay: Assays are performed in 96-well plates in a total volume of 200 μl/well. Compounds are dissolved in dimethylsulfoxide (DMSO) and added to plates in a volume of 10 μl followed by addition of 165 μl of assay mix. Plates are pre-incubated at 25° C. for 15 min and the reactions are initiated by the addition of 25 μl of cAMP followed by thorough mixing. Reaction rates are measured by monitoring the decrease in fluorescence using excitation at 355 nm and emission at 460 nm for a period of 10 min in a fluorescence plate reader. Initial rates (slopes) are determined from linear portions of the progress curves. Final concentrations of assay components are as follows: 50 mM Tris, pH 8, 10 mM MgCl2, 50 mM KCl, 2% DMSO, 5 mM tris(2-carboxyethyl)phosphine (TCEP), 0.4 mM phosphenolpyruvate (PEP), 0.01 mM NADH, 0.04 mM adenosine triphosphate (ATP), 0.004 mM cAMP, 7.5 units myokinase from yeast, 1.6 units pyruvate kinase, 2 units lactate dehydrogenase, and either 0.5 nM human PDE4D7 or 10 nM human PDE4B1. All data are percent normalized relative to controls and are presented as percent inhibition. An inhibitory concentration 50% (IC50) value is calculated by fitting of a sigmoidal dose response curve. Human PDE4D7 contained a mutation of serine 54 to aspartic acid to mimic activation by cAMP-dependent protein kinase A (PKA). Human PDE4B1 contained a corresponding mutation of serine 133 to aspartic acid to also mimic PKA activation.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 391.9, ALogP 4.92, HBA 3, HBD 2, PSA 54.02, QED 0.65
Compound (SMILES): C=CC(=O)N1CCC(n2nc(-c3cc(C=O)n(C)n3)c3c(N)ncnc32)C1
InChIKey: LNASRTLHHDPXCY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 catalytic domain (781 to 1124 residues) expressed in baculovirus expression system using TK-biotin as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 70.4 nM (pChEMBL 7.150000095367432)
Descriptors: MW 366.39, ALogP 0.58, HBA 9, HBD 1, PSA 124.82, QED 0.53
Compound (SMILES): CCOC(=O)[C@H](C)N[P@@](=O)(CC/C=C(\C)CO)Oc1ccccc1
InChIKey: YGSLLMNEAQXTQJ-RBEULTJKSA-N
Target: Butyrophilin subfamily 3 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00481
Assay: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA
Measurement: EC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 355.37, ALogP 3.13, HBA 5, HBD 2, PSA 84.86, QED 0.38
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccc(C(F)(F)F)cc2)C(=O)CN(Cc2ccccc2C(F)(F)F)S(=O)(=O)c2ccc(F)cc2)cc1
InChIKey: NQSRGIZQPUUKDT-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 expressed in SF9 baculoviral system using FAM-labeled acetylated peptide as substrate by EMSA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 683.6, ALogP 6.41, HBA 5, HBD 2, PSA 107.02, QED 0.11
Compound (SMILES): N#Cc1ccc(N2CCC(C(=O)N3N=CC[C@H]3c3cc(F)cc(F)c3)CC2)nn1
InChIKey: LRSFJHOMTHDOLZ-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIP1 in human U937 cells assessed as reduction in TNFalpha/QVD-Oph-induced necroptosis measured after 24 hrs by cell titer-glo luminescent cell viability assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 396.4, ALogP 2.8, HBA 6, HBD 0, PSA 85.48, QED 0.8
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3ccc(N)nc3)c(O)cc2Br)C1=O
InChIKey: PELLLOGHRNZVIV-RZNTYIFUSA-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 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 436.29, ALogP 3.38, HBA 7, HBD 2, PSA 105.75, QED 0.71
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCC5(CCCNC5)CC4)cc3)sc2n1
InChIKey: ZJRQDCSKGNNTNV-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 463.65, ALogP 4.13, HBA 6, HBD 3, PSA 83.28, QED 0.53
Compound (SMILES): Cl.NOC(c1ccccc1)c1ccc(Cl)c(Cl)c1
InChIKey: PBZNCQQGLHOIGW-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO (unknown origin) using L-tryptophan as substrate by spectrophotometric method
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 268.14, ALogP 3.97, HBA 2, HBD 1, PSA 35.25, QED 0.85
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2OCO[C@H]21
InChIKey: JUSWNBNJCUGXNH-WHEJUCFXSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q3UR32
Assay: Antagonist activity at P2X3R in mouse TG sensory neurons assessed as inhibition of P2X3R agonist alpha,beta-meATP-induced current at -65 mV holding potential by whole cell voltage clamp method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 519.19, ALogP -0.61, HBA 14, HBD 5, PSA 257.13, QED 0.27
Compound (SMILES): C=C1CCC(c2ccc(O)cc2)CC1
InChIKey: YGKNWJASJUQVMN-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at estrogen receptor alpha (unknown origin) after 22 hrs by cell-based luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 188.27, ALogP 3.61, HBA 1, HBD 1, PSA 20.23, QED 0.67
Compound (SMILES): COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1OCC(=O)NC1CCCCC1
InChIKey: VAWMVQAKEDXTNH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of recombinant human N-terminal GST/His6-tagged CDK1 (M1 to M297 residues)/CyclinB1 (M1 to V433 residues) expressed in Sf9 insect cells using RBCTF as substrate measured after 1 hr by ADP-glo luminescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 407.47, ALogP 3.43, HBA 5, HBD 2, PSA 93.31, QED 0.65
Compound (SMILES): O=[N+]([O-])c1ccc(/C=N/Nc2nnc(-c3ccncc3)o2)cc1
InChIKey: NFJFOCDCCGFTGX-CXUHLZMHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR catalytic domain (668 to 1210 residues) expressed in baculovirus expression system using TK-biotin peptide as substrate measured after 10 mins by HTRF assay
Measurement: IC50 = 412.3 nM (pChEMBL 6.380000114440918)
Descriptors: MW 310.27, ALogP 2.49, HBA 8, HBD 1, PSA 119.34, QED 0.44
Compound (SMILES): C/C(=N\NC(=O)c1nc(N)n(-c2ccc(S(N)(=O)=O)cc2)n1)c1ccncc1
InChIKey: GMKRIMHCHCHCCT-UFFVCSGVSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 400.42, ALogP 0.05, HBA 9, HBD 3, PSA 171.24, QED 0.4
Compound (SMILES): O=C(/C=C/CN1CCCC1)N1CCOc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc21
InChIKey: JMIAHUUVJVWQPL-ONEGZZNKSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin) using FAM-labeled peptide substrate preincubated for 10 mins followed by substrate addition measured after 40 mins by caliper motility shift assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 467.93, ALogP 4.54, HBA 6, HBD 1, PSA 70.59, QED 0.56
Compound (SMILES): COc1ccc(N2CCN(CC(O)COc3cccc4[nH]c5ccccc5c34)CC2)cc1
InChIKey: FSPXYUHQVJZGHG-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P43140
Assay: Antagonistic activity at alpha1A adrenoceptor in Sprague-Dawley rat vas deferens assessed as inhibition of noradrenaline-induced contractions after 0.5 hrs in presence of alpha2/beta adrenoceptor blocker yohimbine, propranolol by Schild plot analysis
Measurement: Kd = 1862.09 nM (pChEMBL 5.730000019073486)
Descriptors: MW 431.54, ALogP 3.89, HBA 5, HBD 2, PSA 60.96, QED 0.46
Compound (SMILES): O=C(C1=C(O)C(=O)N(c2ccc(Br)cc2F)C1C1CCCCC1)c1ccccc1
InChIKey: HULVCFFGXHJBLU-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Displacement of [3H]-CCR2-RA-[R] from human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor after 120 mins by scintillation spectrometry
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 458.33, ALogP 5.58, HBA 3, HBD 1, PSA 57.61, QED 0.61
Compound (SMILES): O=C1N(c2ccc(-c3ccccc3)cc2)C(=O)C2(CCNCC2)N1c1ncccn1
InChIKey: DIFDHZPOYNCBOH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of KDM4A (unknown origin) using H3 K9Me3 (1 to 15 residues) as substrate
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 399.45, ALogP 3.24, HBA 5, HBD 1, PSA 78.43, QED 0.68
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of IL-23 induced STAT3 phosphorylation in human Jurkat cells incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CC(C)(C)c1cc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)ccc1O
InChIKey: FQPMECRNRDRAPV-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 375.43, ALogP 3.13, HBA 7, HBD 2, PSA 98.44, QED 0.56
Compound (SMILES): CC(C)(C)OC(=O)N(Cc1ccc(C(C)(C)C)cc1)c1ccc(C(=O)NO)cc1
InChIKey: SZBZYDVFLPQCJT-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in baculovirus infected Sf9 cells using FAM-RHKK-TFAc as substrate incubated for 17 hrs by electrophoretic mobility shift assay
Measurement: IC50 = 837 nM (pChEMBL 6.079999923706055)
Descriptors: MW 398.5, ALogP 5.04, HBA 4, HBD 2, PSA 78.87, QED 0.56
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5ccc(-c6cccnc6)cc5)CC4)cn3)nccc12
InChIKey: JRDMCDIQZVMPPB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 246 nM (pChEMBL 6.610000133514404)
Descriptors: MW 477.57, ALogP 3.99, HBA 7, HBD 1, PSA 92.59, QED 0.4
Compound (SMILES): COc1nc2ccc(C(O)(c3ccc(C)nc3C)c3cnnn3C)cc2c(Cl)c1C
InChIKey: ACQHAIZGTGISMN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: RORgammat ThermoFluor Assay: For the RORγt construct used in the ThermoFluor® assay, numbering for the nucleotide sequences was based on the reference sequence for human RORγt, transcript variant 2, NCBI Accession: NM_001001523.1 (SEQ ID NO:1). Nucleotides 850-1635 (SEQ ID NO:2) coding for the wild type human RORγt ligand binding domain (RORγt LBD) were cloned into the pHIS1 vector, a modified pET E. coli expression vector (Accelagen, San Diego), containing an in-frame N-terminal His-tag and a TurboTEV protease cleavage site (ENLYFQG, SEQ ID NO:3) upstream of the cloned insert sequence. The amino acid sequence for the RORγt construct used in the Thermofluor® assay is shown as SEQ ID NO:4.ThermoFluor® experiments were carried out using instruments owned by Janssen Research and Discovery, L.L.C. through its acquisition of 3-Dimensional Pharmaceuticals, Inc. 1,8-ANS (Invitrogen) was used as a fluorescent dye. Protein and compound solutions are dispensed into black 384-well polypropylene PCR microplates (Abgene) and overlayed with silicone oil (1 μL, Fluka, type DC 200) to prevent evaporation.Bar-coded assay plates are robotically loaded onto a thermostatically controlled PCR-type thermal block and then heated at a typical ramp-rate of 1° C./min for all experiments. Fluorescence was measured by continuous illumination with UV light (Hamamatsu LC6) supplied via fiber optic and filtered through a band-pass filter (380-400 nm; >6 OD cutoff). Fluorescence emission of the entire 384-well plate was detected by measuring light intensity using a CCD camera (Sensys, Roper Scientific) filtered to detect 500±25 nm, resulting in simultaneous and independent readings of all 384 wells. Images were collected at each temperature, and the sum of the pixel intensity in a given area of the assay plate was recorded versus temperature. Reference wells contained RORγt without compounds, and the assay conditions were as follows:0.065 mg/mL RORγt60 M 1,8-ANS100 mM Hepes, pH 7.010 mM NaCl2.5 mM GSH0.002% Tween-20Project compounds were arranged in a pre-dosed mother plate (Greiner Bio-one) wherein compounds are serially diluted in 100% DMSO by 1:2 from a high concentration of 10 mM over 12 columns within a series (column 12 is a reference well containing DMSO, no compound). The compounds were robotically dispensed directly into assay plates (1x=46 nL) using a Hummingbird capillary liquid handling instrument (Digilab). Following compound dispense, protein and dye in buffer was added to achieve the final assay volume of 3 μL, followed by 1 μL of silicone oil.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 423.9, ALogP 3.63, HBA 7, HBD 1, PSA 85.95, QED 0.54
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(C(F)(F)F)cn2)cc1Nc1cccc(-c2ncn(C)n2)c1OC
InChIKey: WIXZZUOTUAIJAZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by in vitro patch clamp method
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 498.47, ALogP 4.15, HBA 9, HBD 3, PSA 118.88, QED 0.35
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@@H](C)c3ccc(N4CC5CCC(C4)N5)c(C#N)c3)sc2n1
InChIKey: NSXWVLYZUZRLNB-FTXHTYHOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). 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 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). 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 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 460.61, ALogP 3.53, HBA 7, HBD 3, PSA 107.07, QED 0.54
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)ccc3oc4ccc(-c5cccnc5)cc4c32)c1
InChIKey: FVCDPGCMEGFTQT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) by ADP-gloassay
Measurement: IC50 = 2821 nM (pChEMBL 5.550000190734863)
Descriptors: MW 407.43, ALogP 4.92, HBA 5, HBD 1, PSA 77.13, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cccc(-c2c(-c3ccccc3OC)oc3ncnc(N[C@H](CO)c4ccccc4)c23)c1
InChIKey: PDGXQCBYLSUPPW-HSZRJFAPSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of GST-tagged human EGFR A763_Y764insFHEA mutant using poly(Glu, Tyr) 4:1 substrate incubated for 120 mins by kinase-Glo plus luminescent kinase assay
Measurement: IC50 = 0.145 nM (pChEMBL 9.84000015258789)
Descriptors: MW 506.56, ALogP 5.84, HBA 7, HBD 3, PSA 109.51, QED 0.22
Compound (SMILES): NS(=O)(=O)c1ccc(-c2noc(-c3ccncc3)n2)cc1
InChIKey: BLIIAHGNPLZXHR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as reduction in CO2 hydration after 15 mins by phenol red staining-based stopped flow assay
Measurement: Ki = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 302.31, ALogP 1.45, HBA 6, HBD 1, PSA 111.97, QED 0.78
Compound (SMILES): C[C@@H](O)c1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)cc3)sc2n1
InChIKey: BNTQUFKUUAKTHO-CQSZACIVSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 425.56, ALogP 2.31, HBA 7, HBD 4, PSA 103.51, QED 0.48
Compound (SMILES): Cc1c(-c2ccncc2)ccc2c1CCNC2=O
InChIKey: YTAWESHUWVTJNG-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 21379.62 nM (pChEMBL 4.670000076293945)
Descriptors: MW 238.29, ALogP 2.34, HBA 2, HBD 1, PSA 41.99, QED 0.83
Compound (SMILES): Cc1cc(C)cc(Oc2cccc(-c3c(C)nnn3C3CCN(C(=N)N)CC3)n2)c1
InChIKey: LTVHUTQVMLLORB-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51531
Assay: Binding affinity to human partial length SMARCA2 (S1377 to Q1486 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 100000 nM (pChEMBL 4)
Descriptors: MW 405.51, ALogP 3.59, HBA 6, HBD 2, PSA 105.94, QED 0.51
Compound (SMILES): CCc1ccc(C(=O)Nc2cc(CN3CCN(C)CC3)cc(C(F)(F)F)c2)cc1-c1cccc(-c2cnc3ccnn3c2)c1
InChIKey: WWIJZOWOWLGRSG-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of human recombinant His-tagged c-Kit cytoplasmic domain (544 to 976 residues) expressed in baculovirus expression system using Ser/Thr 6 peptide as substrate after 1 hr in presence of 300 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 598.67, ALogP 6.64, HBA 6, HBD 1, PSA 65.77, QED 0.23
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Affinity Biochemical interaction: (Scintillation proximity assay (SPA)) EUB0000230b CARM1
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1c(C(O)CN2CCN(CC(O)c3ccc4c(c3C)COC4=O)CC2)ccc2c1COC2=O
InChIKey: OCKGFTQIICXDQW-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of ROMK (unknown origin) after 30 mins by 86Rb+ efflux assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 466.53, ALogP 2.03, HBA 8, HBD 2, PSA 99.54, QED 0.62
Compound (SMILES): Nc1nc(-c2ccco2)nc2sc(-c3ccco3)nc12
InChIKey: YXLDLDOAWIUYIS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of NECA-induced increase in cAMP accumulation preincubated for 10 mins followed by NECA addition by GloSensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 284.3, ALogP 3.19, HBA 7, HBD 1, PSA 90.97, QED 0.61
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1ccc(C(c2ccccc2)C2CCCCC2)s1)C(=O)O
InChIKey: YWIWDKUPBIGREM-YMXDCFFPSA-N
Target: C3a anaphylatoxin chemotactic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16581
Assay: Agonist activity at C3a receptor in human MDM cells assessed as induction of intracellular calcium release measured at 1 sec interval for => 200 secs by Fluo-3 AM dye-based FLIPR assay
Measurement: EC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 456.61, ALogP 3.91, HBA 4, HBD 5, PSA 128.3, QED 0.21
Compound (SMILES): CC(=C(C#N)C#N)c1ccc(Cl)cc1Cl
InChIKey: RWPPWZBSTCNQJJ-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-1/beta-3/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P28472
Assay: Positive allosteric modulation of GABA-A alpha1beta3(N265S)gamma2S mutant receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as increase in GABA-induced chloride current after 15 mins at -70 mV holding potential by two-microelectrode voltage clamp method
Measurement: EC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 237.09, ALogP 3.81, HBA 2, HBD 0, PSA 47.58, QED 0.7
Compound (SMILES): CC(=O)N1CCN(c2ccc(CN3CCCC[C@H](c4ccccc4)S3(=O)=O)c(F)c2)CC1
InChIKey: JPIGRPKUSPPFJN-XMMPIXPASA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at GAL4-fused human RORb expressed in HEK293 cells assessed as activation of basal transcriptional activity by dual-glo luciferase reporter gene assay
Measurement: EC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 459.59, ALogP 3.55, HBA 4, HBD 0, PSA 60.93, QED 0.7
Compound (SMILES): COc1ccc(Cn2c(=O)n(C)c3c4cc(-c5cnc(OC)c(NS(C)(=O)=O)c5)ccc4ncc32)cc1
InChIKey: MIXCNAMMWZBDMS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) assessed as reduction in p70S6K phosphorylation
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 519.58, ALogP 3.39, HBA 9, HBD 1, PSA 117.34, QED 0.35
Compound (SMILES): Cc1cn(-c2cc(NC(=O)c3ccc4c(c3)C[C@H](N(C)c3cncnc3)C4)cc(C3CCCCC3)c2)cn1
InChIKey: RRDOCDRBWLWBJS-MUUNZHRXSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of His-tagged human TrkB expressed in baculovirus expression system using Tyr1 peptide as substrate after 1.5 hrs by FRET-based Z-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 506.65, ALogP 5.87, HBA 6, HBD 1, PSA 75.94, QED 0.35
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccc(Cl)cc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N2
InChIKey: KKRGXDSPEUYYKM-XIQIEEFNSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase using MeOSuc-AAPV-MCA as substrate at pH 7.2 and 298 K measured every 60 secs for 600 secs
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1626.19
Compound (SMILES): N=C(N)N(CCCCN1CCN(CCCCCCCOc2ccccc2)CC1)Cc1ccc([N+](=O)[O-])cc1
InChIKey: SAZDSXKHNDLLLA-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]-Nalpha-Methylhistamine from recombinant human histamine H3 receptor expressed in HEK293 cells after 1 hr by liquid scintillation counting analysis
Measurement: Ki = 144.54 nM (pChEMBL 6.840000152587891)
Descriptors: MW 524.71, ALogP 4.72, HBA 6, HBD 2, PSA 111.96, QED 0.1
Compound (SMILES): COc1c(C(C)(C)C)cc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1C(C)(C)C
InChIKey: SAVMBELDOOXVNX-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of NECA-stimulated adenylyl cyclase activity by Glo-sensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 445.57, ALogP 4.73, HBA 7, HBD 1, PSA 87.44, QED 0.49
Compound (SMILES): CCc1cc(O)c(F)cc1-c1cc(NS(=O)(=O)c2ccccc2Cl)c2cn[nH]c2c1
InChIKey: VPIZBXRPGLRGBT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human Gst-tagged JAK1 (850 to 1154 residues) expressed in baculovirus using biotin-synthetic peptide as substrate after 40 mins by HTRF assay
Measurement: IC50 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 445.9, ALogP 5.09, HBA 4, HBD 3, PSA 95.08, QED 0.4
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z′-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen Biochemical Kinase Profiling Service. The Z′-LYTE biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores one at each end that make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophore on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(N)=O)C(C)C
InChIKey: RSJQKOKDULPIQY-RUAREOIKSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 30 mins by IP1 accumulation assay
Measurement: EC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 897.06, ALogP -3.8, HBA 12, HBD 15, PSA 393.64, QED 0.02
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(Cc2ccccc2)C3)n(C)c1=O
InChIKey: BZDHUIDJDDKOMY-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Displacement of [3H]CCPA from rat A1 receptor by liquid scintillation counting method
Measurement: Ki = 79.3 nM (pChEMBL 7.099999904632568)
Descriptors: MW 325.37, ALogP 0.45, HBA 7, HBD 0, PSA 65.06, QED 0.69
Compound (SMILES): CN(C)C(=O)Cn1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)cc4)CC3)no2)cn1
InChIKey: VAAPYECJHQQRAS-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Affinity Biochemical interaction (Binding assay (measuring radio-labeled ligand [125I]-L-691831(PE NEX084) displacement)) EUB0000740a ALOX5AP
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 430.47, ALogP 2.14, HBA 9, HBD 1, PSA 128.85, QED 0.49
Compound (SMILES): COc1ccccc1-c1noc(-c2csc(S(N)(=O)=O)c2)n1
InChIKey: LFMWAEICMWTFDY-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as reduction in CO2 hydration after 15 mins by phenol red staining-based stopped flow assay
Measurement: Ki = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 337.38, ALogP 2.12, HBA 7, HBD 1, PSA 108.31, QED 0.78
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cccc(S(N)(=O)=O)c2)c1
InChIKey: AVDQKWNDTMPNLC-HXUWFJFHSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 490.58, ALogP 1.85, HBA 6, HBD 4, PSA 158.9, QED 0.11
Compound (SMILES): C(=N/c1c2c(nc3ccccc13)CCCC2)\c1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
InChIKey: RBCHVNJEMYCRCK-FADJLKOXSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE assessed as dissociation constant for enzyme-substrate-inhibitor complex using butyrylthiocholine iodide as substrate measured for 125 secs by Ellman's method
Measurement: Ki = 173 nM (pChEMBL 6.760000228881836)
Descriptors: MW 498.63, ALogP 8.02, HBA 4, HBD 0, PSA 43.71, QED 0.2
Compound (SMILES): Nc1c(C(=O)NCCc2ccc(N3CCNCC3)c(Cl)c2)sc2nc(C(F)F)ccc12
InChIKey: RWOYNAVVEALDEO-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). 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 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). 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 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 465.96, ALogP 3.85, HBA 6, HBD 3, PSA 83.28, QED 0.51
Compound (SMILES): NS(=O)(=O)c1nnc(NC(=O)/C(Cc2ccccc2)=N/OCc2ccccc2)s1
InChIKey: OUSPVPRHYSQACR-HZHRSRAPSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 expressed in Escherichia coli by stopped-flow CO2 hydration assay
Measurement: Ki = 39.1 nM (pChEMBL 7.409999847412109)
Descriptors: MW 431.5, ALogP 1.94, HBA 8, HBD 2, PSA 136.63, QED 0.32
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CCCCCCCCCCCCCCC(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: ISOOOILKNZMRMU-YNNVFSJPSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.011 nM (pChEMBL 10.960000038146973)
Descriptors: MW 3490.96
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood assessed as reduction in anti-human IgE antibody-stimulated histamine release pretreated for 2 hrs followed by anti-human IgE antibody-stimulation and measured after 30 mins by ELISA
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): Cc1c(Cl)cccc1OCc1cc(=O)n2nc(-c3ccccc3)nc2[nH]1
InChIKey: DHVPJCVPOZYDTH-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Binding affinity to human FABP3 expressed in Escherichia coli assessed as degree of fluorescent shift by temperature-dependent fluorescence thermal shift assay
Measurement: Kd = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 366.81, ALogP 3.63, HBA 5, HBD 1, PSA 72.28, QED 0.6
Compound (SMILES): COc1ncc(-c2cc3c(c(OCCN4CCC(C(C)(C)O)CC4)c2F)COC3)cc1NS(C)(=O)=O
InChIKey: LMYUCGSFQCEING-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p120gamma expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of biotin-PIP3 by HTRF assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 523.63, ALogP 3.16, HBA 8, HBD 2, PSA 110.22, QED 0.52
Compound (SMILES): CC(C)[C@H](NC(=O)C1CCN(c2nc(N3CCOCC3)nc(-n3c(C(F)F)nc4ccccc43)n2)CC1)C(N)=O
InChIKey: OQFVGRSPRONFDZ-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) expressed in baculovirus expression system by kinase-glo luminescence assay
Measurement: IC50 = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 557.61, ALogP 1.83, HBA 10, HBD 2, PSA 144.39, QED 0.42
Compound (SMILES): COc1ccc(S(=O)(=O)N2C(=O)NC3(CCCc4ccccc43)C2=O)cc1
InChIKey: KQNAXJYPBMYCPP-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR2 in rat sciatic nerve assessed as reduction in sorbitol accumulation incubated for 3 hrs in presence of 28 mM glucose by gas chromatographic analysis
Measurement: IC50 = 19420 nM (pChEMBL 4.710000038146973)
Descriptors: MW 386.43, ALogP 2.17, HBA 5, HBD 1, PSA 92.78, QED 0.82
Compound (SMILES): NCc1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)c4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: HVEXWDUPQQGDSO-BYQQZPSGSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human f10a using Mes-DArg-Pro-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 794.98, ALogP 2.37, HBA 9, HBD 6, PSA 195.07, QED 0.16
Compound (SMILES): CCCC1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN3C(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CO)NC1=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](Cc1ccc(-c3ccccc3)cc1)C(=O)N2
InChIKey: LRHBPVVPFQMQPP-GZBZYHQTSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibition of recombinant human chymase expressed in Pichia pastoris using NleTDY-pNA as substrate by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1629.88
Compound (SMILES): CCC(CC)CNc1c(C(N)=O)cnc2ccc(-c3ccc(COC)nc3)cc12
InChIKey: JBYTYXUMXMLDNQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 392.5, ALogP 4.39, HBA 5, HBD 2, PSA 90.13, QED 0.56
Compound (SMILES): CC(C)(C)c1ccc(CN(C(=O)CNS(=O)(=O)c2ccc(F)cc2)c2ccc(C(=O)NO)cc2)cc1
InChIKey: JXKKJJUGFLVTAG-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in baculovirus infected Sf9 cells using FAM-RHKK-TFAc as substrate incubated for 17 hrs by electrophoretic mobility shift assay
Measurement: IC50 = 665 nM (pChEMBL 6.179999828338623)
Descriptors: MW 513.59, ALogP 3.75, HBA 5, HBD 3, PSA 115.81, QED 0.31
Compound (SMILES): O=C1c2ccccc2S(=O)(=O)N1CC1CC(c2ccccn2)=NO1
InChIKey: YUEBWSMNSRVZGP-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 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 343.36, ALogP 1.42, HBA 6, HBD 0, PSA 88.93, QED 0.84
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(COC)C[C@H]43)c2)cn1
InChIKey: IPUJINDWAGRAHN-KNXBSLHKSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of recombinant human BACE2 expressed in HEK293 cells co-transfected with N-terminal HA-tagged/C-terminal Myc tagged Mbeta chain of human PMEL17 measured after overnight incubation by Gaussia luciferase reporter gene assay
Measurement: IC50 = 569 nM (pChEMBL 6.25)
Descriptors: MW 473.51, ALogP 2.7, HBA 8, HBD 2, PSA 111.72, QED 0.59
Compound (SMILES): N#Cc1c(O)c2ccncc2[nH]c1=O
InChIKey: NPAMRWDIMURYSE-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of full length human KDM5B using biotinylated H2NART(KMe3)QTARKSTGGKAPRKQLA-NTPEG-biotin as substrate after 30 to 40 mins using 2 uM of 2-OG as co-substrate by TR-FRET assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 187.16, ALogP 0.5, HBA 4, HBD 2, PSA 89.77, QED 0.63
Compound (SMILES): C[C@@H]1CN(c2cc(-c3nn(C)c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1
InChIKey: YGCZGTCXWBPTDC-GASCZTMLSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 1071.52 nM (pChEMBL 5.96999979019165)
Descriptors: MW 393.49, ALogP 3.58, HBA 7, HBD 0, PSA 65.3, QED 0.68
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCn4cc(CCCOc5ccc6c(=O)cc(-c7ccccc7)oc6c5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: NBPXQCGXCNLDOF-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 616.3 nM (pChEMBL 6.210000038146973)
Descriptors: MW 819.87, ALogP 8.3, HBA 13, HBD 0, PSA 154.35, QED 0.06
Compound (SMILES): Cc1cnc(Nc2ccc(N3CCC(N(C)CCCO)CC3)c(F)c2)nc1-c1cnn(C(C)C)c1
InChIKey: BAHGOININFNXCT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 (564 to end residues) using EAIYAAPFAKKK as substrate after 40 mins in presence of [gamma33P]-ATP by scintillation counting based radiometric assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 481.62, ALogP 4.4, HBA 8, HBD 2, PSA 82.34, QED 0.47
Compound (SMILES): O=C(Nc1nnc(-c2ccncc2)s1)c1cc(Cl)nc2ccccc12
InChIKey: GKNABSCIYYIYLB-UHFFFAOYSA-N
Target: DNA dC->dU-editing enzyme APOBEC-3G (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC16
Assay: Inhibition of recombinant APOBEC3G (unknown origin) expressed in HEK293 cells assessed as reduction in cytosine deaminase activity using 5'-6-FAM and 3'-TAMRA quench molecule tagged cytosine-containing single-stranded DNA substrate incubated for 2 hrs by fluorescence-based assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 367.82, ALogP 4.05, HBA 6, HBD 1, PSA 80.66, QED 0.55
Compound (SMILES): CCN1CCC(c2cnn(-c3nccc4c(=O)[nH]cnc34)c2)CC1
InChIKey: CLDDHWNJFOWJLH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 324.39, ALogP 1.7, HBA 6, HBD 1, PSA 79.7, QED 0.79
Compound (SMILES): COCC(=O)NC1CCN(Cc2cc3nc(-c4cnc(N)nc4)nc(N4CCOCC4)c3s2)C1
InChIKey: DISXGKPKWGNTKB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 484.59, ALogP 0.9, HBA 11, HBD 2, PSA 131.62, QED 0.5
Compound (SMILES): Cl.O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1ccc2sccc2c1
InChIKey: CUQZYQNFUYFGAN-HBJKKLOVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at recombinant mouse mu opioid receptor expressed in CHO cell membrane assessed as [35]-GTPgammaS binding incubated for 1.5 hrs by scintillation counting method
Measurement: EC50 = 2.47 nM (pChEMBL 8.609999656677246)
Descriptors: MW 502.64, ALogP 3.97, HBA 6, HBD 3, PSA 82.03, QED 0.5