lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1ccnc2[nH]c(-c3ccc(N4CCNCC4)cc3)cc12
InChIKey: NVTWXXPKCOGVMK-UHFFFAOYSA-N
Target: Cell division cycle 7-related protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O00311
Assay: Inhibition of CDC7 (unknown origin)
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 303.37, ALogP 2.51, HBA 4, HBD 2, PSA 67.74, QED 0.76
Compound (SMILES): CC1CCN(CCCN2C(=O)CCc3ccccc32)CC1
InChIKey: PRYVZXFJJBFQRT-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human dopamine D4 receptor expressed in HEK293 cell membranes after 1 hr by scintillation counting method
Measurement: Ki = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 286.42, ALogP 3.09, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): C#CCOc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1
InChIKey: OGSJBMHENPCLPK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in yeast microsomal membranes using 7-ethoxy-methyloxy-3-cyanocoumarin as substrate by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 276.3, ALogP 2.6, HBA 3, HBD 1, PSA 54.98, QED 0.75
Compound (SMILES): CN1CC[C@]23c4c5ccc(O)c4O[C@H]2CCC[C@@]3(O)[C@H]1C5
InChIKey: FRHCZTIUUCWDEE-DLTLXFJOSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-HS665 from recombinant human KOR expressed in CHO cell membranes after 30 mins by liquid scintillation counting
Measurement: Ki = 21.6 nM (pChEMBL 7.670000076293945)
Descriptors: MW 287.36, ALogP 1.57, HBA 4, HBD 2, PSA 52.93, QED 0.76
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)c(=O)[nH]c1ccccc12
InChIKey: UTNZTKXNTBTXTL-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin receptor kinase (unknown origin) using TK as substrate after 30 mins by HTRF assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 550.04, ALogP 5.8, HBA 8, HBD 3, PSA 126.07, QED 0.22
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CN1CCNCC1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)O
InChIKey: FGYQREJLQGOMTG-XKIFMCPMSA-N
Target: Neuromedin-U receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BZ39
Assay: Agonist activity at mouse NMUR2 expressed in CHO cells assessed as increase in intracellular calcium influx after 180 secs by Fluo 4-AM dye based FLIPR assay
Measurement: EC50 = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 1288.52
Compound (SMILES): c1ccc(Oc2cccc(NCc3nc(-c4ccncc4)n[nH]3)c2)cc1
InChIKey: RSCLSNKPENXWDW-UHFFFAOYSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Homo sapiens
UniProt: P17252
Assay: Inhibition of human PKCalpha active using MBP as substrate after 60 mins in presence of [gamma-32]ATP by scintillation counting
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 343.39, ALogP 4.27, HBA 5, HBD 2, PSA 75.72, QED 0.55
Compound (SMILES): CC(C)[C@@H](CO)Nc1ccc2ncc(-c3cccnc3)n2n1
InChIKey: VBYRFFCBZNEHAL-CYBMUJFWSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant CDK9/cyclin T expressed in insect cells using CDK7/9-tide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 297.36, ALogP 2.22, HBA 6, HBD 2, PSA 75.34, QED 0.76
Compound (SMILES): CCCn1c(Oc2ccc(F)c(F)c2)nc2nc(C3CCCC3)[nH]c2c1=O
InChIKey: UUGKUAPXWUSTOD-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in HEK293 cell membranes after 90 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.39, ALogP 4.26, HBA 5, HBD 1, PSA 72.8, QED 0.72
Compound (SMILES): C#CCN(CCCCOc1ccc2c(c1)NC(=O)CC2)Cc1ccccc1
InChIKey: WUVKEPSRWQCJFN-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of 5% rat cortex homogenate AChE using acetylthiocholine chloride as substrate after 15 mins by Ellman's method
Measurement: IC50 = 23300 nM (pChEMBL 4.630000114440918)
Descriptors: MW 362.47, ALogP 3.87, HBA 3, HBD 1, PSA 41.57, QED 0.54
Compound (SMILES): COc1ccccc1CN1C[C@H](c2cn(C)c3ccccc23)[C@@H](N(C)C)C1
InChIKey: CXQQECCQTKSQKN-IRLDBZIGSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: Binding affinity to his tagged EED (1 to 441 residues) (unknown origin) incubated for 20 mins in presence of biotinylated H3K27me3 peptide (19 to 33 residues) by alphascreen competitive binding assay
Measurement: IC50 = 1570 nM (pChEMBL 5.800000190734863)
Descriptors: MW 363.51, ALogP 3.72, HBA 4, HBD 0, PSA 20.64, QED 0.69
Compound (SMILES): Cc1csc2nc(C(=O)NCc3cccc(CNC(=O)Cc4nc[nH]n4)c3)[nH]c(=O)c12
InChIKey: JRBXTZBABOIXPG-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of APMA-activated recombinant human MMP-8 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 437.49, ALogP 1.2, HBA 7, HBD 4, PSA 145.52, QED 0.34
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](Cc4c[nH]c5ccccc45)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c4ccccc14)C(=O)N3)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N2
InChIKey: MMRKGTJWQNIZFW-VNINGPJYSA-N
Target: Lethal factor (SINGLE PROTEIN), Bacillus anthracis
UniProt: P15917
Assay: Inhibition of Bacillus anthracis lethal factor protease preincubated for 30 mins prior to addition of substrate containing fluorescent proteins CyPet and YPet measured every 2 mins for 3 hrs in presence of 0.1% BSA by FRET assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 2607.2
Compound (SMILES): C=CC(=O)N1C[C@@H](C)C[C@@H](Nc2ncnc3[nH]ccc23)C1
InChIKey: TVXJKTOQQYIZSA-WDEREUQCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: JAK Caliper Enzyme Assay: Test article was solubilized in dimethyl sulfoxide (DMSO) to a stock concentration of 30 mM. An 11-point half log dilution series was created in DMSO with a top concentration of 600 μM. The test compound plate also contained positive control wells containing a known inhibitor to define 100% inhibition and negative control wells containing DMSO to define no inhibition. The compound plates were diluted 1 to 60 resulting in a top final assay compound concentration of 10 μM and a 2% DMSO concentration.Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 4 μM ATP and 1 μM peptide substrate. The JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition 1 nM JAK3 enzyme and were incubated at room temperature 75 minutes for JAK3. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4. The assay plates were placed on a Caliper Life Science Lab Chip 3000 (LC3000) instrument, and each well was sampled using appropriate separation conditions to measure the unphosphorylated and phosphorylated peptide.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 285.35, ALogP 1.79, HBA 4, HBD 2, PSA 73.91, QED 0.84
Compound (SMILES): O=C(O)C[C@@H]1N=C(c2ccccc2)c2ccccc2N(CCCCC(=O)NO)C1=O
InChIKey: XQMOVPWUZIEWBO-KRWDZBQOSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human KDAC6 using FITC-labeled histone H4 acetylated peptide as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 19840 nM (pChEMBL 4.699999809265137)
Descriptors: MW 409.44, ALogP 2.39, HBA 5, HBD 3, PSA 119.3, QED 0.35
Compound (SMILES): Cc1cc(N)nc(CCc2cccc(CCCN(C)C)c2)c1
InChIKey: QSJQTEGTURZDIY-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Mus musculus
UniProt: P29477
Assay: Inhibition of mouse macrophage iNOS expressed in Escherichia coli using L-arginine as substrate assessed as reduction in NO production by measuring oxidation of oxyHb to metHb measured for 6 mins by hemoglobin- NO capture assay
Measurement: Ki = 3458 nM (pChEMBL 5.460000038146973)
Descriptors: MW 297.45, ALogP 3.25, HBA 3, HBD 1, PSA 42.15, QED 0.85
Compound (SMILES): CC(=O)N1CCN(c2cccc(-c3cc(-c4nnc(C(C)C)o4)c4c(N)ncnn34)c2)C(=O)C1(C)C
InChIKey: BZFYKNDIMPKFTP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: ADP-Glo Format PI3K Assay: The ADP-Glo format PI3K assays were performed in Proxiplate 384-well plates (Perkin Elmer #6008280). The final assay volume was 2 μl prepared from 1 μl additions of enzyme/PIP2:PS lipid (Invitrogen #PV5100) mixture and 1 μl ATP (provided in kit, Promega #V9101) and test compounds in assay buffer (50 mM HEPES pH 7.5, 3 mM MgCl2, 100 mM NaCl, 0.5 mM EGTA, 2 mM DTT, 0.03% CHAPS). The reaction was initiated by the combination of enzyme/lipid, ATP, and test compounds. The reaction mixture was incubated at room temperature for 30 minutes (PI3K Alpha, Beta, Gamma) or 3 hours for PI3K Delta. ADP-Glo (2 μl), followed by Kinase Detection reagent (4 μl), were added to reactions following the initial incubation and allowed to incubate 40 minutes at room temperature. The reaction mixture was analyzed on the TOPCOUNT (Perkin Elmer). Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of enzyme in the assays are PI3K Alpha [0.5 nM], PI3K Beta [2 nM], PI3K Gamma [20 nM], PI3K Delta [0.5 nM]. ATP final concentrations are as follows: for Alpha [10 μM], for Beta [12.5 μM], for Gamma [6.5 μM], for Delta [100 μM]. Lipid final concentration was the same for all enzymes, [25 μM]. Dose response curves were generated to determine the concentration required to inhibit 50% of activity. Compounds were dissolved at 0.12 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. The IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 488.55, ALogP 3.13, HBA 9, HBD 1, PSA 135.75, QED 0.46
Compound (SMILES): O=S(=O)(NCCCCN1CC=C(c2c[nH]c3ccc(Cl)cc23)CC1)c1ccc2ccccc2c1
InChIKey: OHLNGDFTLNKGPO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in CHO-K1 cell membranes after 60 mins by scintillation counting
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 494.06, ALogP 5.82, HBA 3, HBD 2, PSA 65.2, QED 0.3
Compound (SMILES): NC(=O)c1sc(Oc2ccc(N)nc2)c2c1CCc1cnsc1-2
InChIKey: MIRNBYWEECOSRO-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P24863
Assay: Inhibition of kinase tracer-236 binding to GST-tagged CDK8/CyclinC (unknown origin) after 60 mins by TR-FRET assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 344.42, ALogP 2.84, HBA 7, HBD 2, PSA 104.12, QED 0.76
Compound (SMILES): Cc1cc(/C=C2\SC(=O)NC2=O)c(C)n1-c1ccc(-c2ccc(/C=C3\SC(=O)NC3=O)c(Cl)c2)cc1
InChIKey: PUKMEKVQVLYPHD-IINORCHSSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of recombinant human MCF7 cells derived His-tagged GAC (L123 to S598 residues) expressed in Escherichia coli C41(DE3)pLysS using glutamine as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by glutamate dehydrogenase coupled enzyme assay
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 536.03, ALogP 6.06, HBA 7, HBD 2, PSA 97.27, QED 0.39
Compound (SMILES): Cl.Cl.O=C(Nc1ccc(O[C@H]2CCNC2)c(-c2ccc(F)cc2)c1)c1ccc(O[C@H]2CCNC2)c(-c2ccc(F)c(F)c2)c1
InChIKey: XSSFZCLVXBYISR-HWTGJJCHSA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Binding affinity to beta-catenin L156S/L159S mutant (unknown origin) expressed in Escherichia coli BL21 DE3 incubated for 3 hrs by fluorescence polarization assay
Measurement: Kd > 12000 nM (pChEMBL 4.921000003814697)
Descriptors: MW 573.62, ALogP 6.17, HBA 5, HBD 3, PSA 71.62, QED 0.24
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3cnn(CC4CC(=O)N(c5ccc(C(F)(F)F)cc5)C4)c3)nc2n(CC)c1=O
InChIKey: VTWJQIYQJKMCSP-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-ZM-241385 from human adenosine receptor A2a expressed in HEK293 cell membranes after 90 mins by liquid scintillation counting method
Measurement: Ki = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 529.52, ALogP 3.25, HBA 8, HBD 1, PSA 110.81, QED 0.4
Compound (SMILES): CC(c1cc2cc(-c3cnn(C)c3)cnc2cc1F)n1nnc2ncc(-c3cnn(CCO)c3)nc21
InChIKey: VLBZFDFQVGAJSP-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 484.5, ALogP 2.77, HBA 11, HBD 1, PSA 125.25, QED 0.38
Compound (SMILES): CC(=O)NCC1Cc2ccccc2N(c2ccccc2)C1
InChIKey: AOXKKYWKHVTVPY-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Displacement of 2-[125I]-Iodomelatonin from human MT1 receptor expressed in CHO cell membranes after 120 mins by filter binding method
Measurement: Ki = 3.02 nM (pChEMBL 8.520000457763672)
Descriptors: MW 280.37, ALogP 3.13, HBA 2, HBD 1, PSA 32.34, QED 0.94
Compound (SMILES): NS(=O)(=O)c1nnc(/N=C/c2ccc(/C=N/c3nnc(S(N)(=O)=O)s3)o2)s1
InChIKey: AIKDTGLXMHXRBM-NPJRDEIVSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human carbonic anhydrase 7 incubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 55.2 nM (pChEMBL 7.260000228881836)
Descriptors: MW 448.49, ALogP -0.22, HBA 13, HBD 2, PSA 209.74, QED 0.48
Compound (SMILES): C[C@@H]1c2nnn(-c3cnccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: DUWZDSOVDZWSMF-SNVBAGLBSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding Assay: human or rat P2X7-1321 N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl: 10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2009, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 2238.7 nM (pChEMBL 5.650000095367432)
Descriptors: MW 422.8, ALogP 3.49, HBA 6, HBD 0, PSA 76.8, QED 0.63
Compound (SMILES): CCc1nc2ccc(N3CCN(Cc4ncon4)CC3)cn2c1N(C)c1nc(-c2ccc(F)cc2)cs1
InChIKey: QDBOUKWVJFPGGY-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Human ENPP2 (hENPP2) Assay: Compound IC50 values are determined in a hENPP2 (UniProtKB/SwissProt Sequence ref Q13822) biochemical assay using LPC as substrate. 5 μL of a dilution series of compound, starting from 20 μM highest concentration, 1/5 dilution, is added to the wells. hENPP2 is used at a final concentration of 1 μg/mL or 3 μg/mL (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration). The enzyme is diluted in 50 mM Tris-HCl pH 8.5, 500 mM NaCl, 5 mM KCl, 10 mM CaCl2, 0.1% fatty acid free BSA in a total volume of 10 μL. the reaction is started by the addition of 10 μL of 150 μM LPC (palmitoyl 16:0) diluted in the same buffer as described above and the mixture is incubated at 37° C. for 30 min. The reaction is terminated and choline quantified by the addition of a 25 μL of a mixture containing 0.6 U/mL of choline oxidase, 0.6 U/mL of peroxydase, 1.8 mM TOOS, 1.2 mM amino-antipyrine, 20 mM EGTA (stop-developer solution) diluted in the buffer described above. Luminescence is read on the Envision after an incubation of 30 min at room temperature (Excitation 555 nm, excitation light=70%).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518.62, ALogP 4.63, HBA 10, HBD 0, PSA 78.83, QED 0.31
Compound (SMILES): COCCN1CCc2[nH]c(-c3ccnc(Nc4ccnn4C)n3)cc2C1=O
InChIKey: HKLUILZKCLFHGM-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated ERK2 levels
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 367.41, ALogP 1.59, HBA 7, HBD 2, PSA 100.96, QED 0.69
Compound (SMILES): CC(=O)N1CCN(c2cc(-c3cc(Cl)c4c(N)ncnn34)ccc2C#N)C(=O)C1(C)C
InChIKey: XHYZQSCPMBJYIL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as reduction in anti-CD3/anti-CD28-mediated IFNgamma production preincubated for 1 hr followed by anti-CD3/anti-CD28 activation measured after overnight incubation by AlphaLisa assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 437.89, ALogP 2.48, HBA 7, HBD 1, PSA 120.62, QED 0.66
Compound (SMILES): O=C1/C(=C\c2cccc(OCc3ccccc3)c2)C(C(F)(F)F)=NN1c1ccccc1
InChIKey: RKYTYINORAMZFG-QNGOZBTKSA-N
Target: LgtC (SINGLE PROTEIN), Neisseria meningitidis
UniProt: Q93EK7
Assay: Inhibition of recombinant Neisseria meningitidis glycosyltransferase LgtC using UDP-Gal/lactose as substrate preincubated for 20 mins with UDP-Gal followed by lactose addition measured after 20 mins in presence of MnCl2
Measurement: Ki = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 422.41, ALogP 5.61, HBA 3, HBD 0, PSA 41.9, QED 0.5
Compound (SMILES): CCOc1cccc(CC[N+](C)(C)C)c1.O=C[O-]
InChIKey: XACHRNHFPGETBF-UHFFFAOYSA-M
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methyl-scopolamine bromide from human recombinant muscarinic M3 receptor expressed in HEK293T cell membranes after 1 hr by liquid scintillation counting method
Measurement: Ki = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 208.32, ALogP 2.33, HBA 1, HBD 0, PSA 9.23, QED 0.67
Compound (SMILES): Cc1nc2n(c(=O)c1CCN1CCN(c3cccc4sccc34)CC1)CCC=C2.Cl
InChIKey: ZUPJZYNGLKKNEJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 37.6 nM (pChEMBL 7.420000076293945)
Descriptors: MW 406.56, ALogP 3.55, HBA 6, HBD 0, PSA 41.37, QED 0.66
Compound (SMILES): CCOC(=O)[C@@]12CCCCC/C=C\1N(Cc1cccc3ccccc13)C(=O)[C@H]2CC(=O)N1CCN(C(=O)c2ccco2)CC1
InChIKey: FDSBKDBYCLRKTL-AGCJQPHOSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of GLUT1 (unknown origin)-mediated glucose uptake expressed in CHO-K1 cells assessed as reduction in ATP synthesis up to 30 mins in presence of mitochondrial function blocker antimycin A
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 597.71, ALogP 5.16, HBA 6, HBD 0, PSA 100.37, QED 0.35
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1Cl)c1nc2cccc(Cl)c2c(=O)n1-c1cc[nH]n1
InChIKey: JSEUAWBEBRLEJF-ZETCQYMHSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of human full length PI3K p110delta/p85 alpha using PIP2/ATP as substrate after 30 mins by TR-FRET assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 432.28, ALogP 2.54, HBA 9, HBD 4, PSA 153.42, QED 0.38
Compound (SMILES): c1ccc2c(c1)CN[C@@H](CN(CCCCNCC1CCOCC1)[C@H]1CCCc3cccnc31)C2
InChIKey: UWRHBQJVXGUUAS-IZLXSDGUSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 462.68, ALogP 4.27, HBA 5, HBD 2, PSA 49.42, QED 0.52
Compound (SMILES): CC(=O)N[C@@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O
InChIKey: SYLVGCUVNFAQGW-FBBJYXRJSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R expressed in HEK293 cells assessed as inhibition of NDP-MSH induced-cAMP accumulation after 2 hrs by alpha screen assay
Measurement: Kd = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 870.79, ALogP 2.92, HBA 6, HBD 7, PSA 212.6, QED 0.04
Compound (SMILES): Cc1nc2n(c(=O)c1CCN1CCN(c3nsc4ccccc34)CC1)CCCC2F
InChIKey: KQBMPESAVRFKMZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 427.55, ALogP 3.33, HBA 7, HBD 0, PSA 54.26, QED 0.64
Compound (SMILES): O=C(O)CCc1cc2cc(Cl)ccc2n1S(=O)(=O)c1ccccc1
InChIKey: KWWUGVCSFKNBOZ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human GAL4-fused PPARgamma LBD expressed in African green monkey COS7 cells co-expressing 5Gal4 pGL3 TK Luc after overnight incubation by luciferase reporter gene assay
Measurement: EC50 = 1558 nM (pChEMBL 5.809999942779541)
Descriptors: MW 363.82, ALogP 3.55, HBA 4, HBD 1, PSA 76.37, QED 0.75
Compound (SMILES): O=S(=O)(Nc1nccs1)c1cc(Cl)c(NCC2CCCC3(C2)OCCO3)cc1F
InChIKey: KMTIXSIYMVUSCD-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 inactivated state form expressed in HEK293 cells at -50 mV holding potential by by automated patch clamp electrophysiology assay
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 461.97, ALogP 4.08, HBA 7, HBD 2, PSA 89.55, QED 0.67
Compound (SMILES): [O-][S+](Cc1cccs1)C(c1ccccc1)c1ccc(Br)cc1
InChIKey: HPPPHPZJRWQZID-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of re-uptake of [3H]-dopamine at human DAT expressed in HEK293 cells preincubated for 5 mins followed by [3H]-dopamine addition measured after 1 min by liquid scintillation counting
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 391.36, ALogP 5.55, HBA 2, HBD 0, PSA 23.06, QED 0.52
Compound (SMILES): Cc1n[nH]c2ccc(-c3cc(N[C@@H](CO)c4ccccc4)cnc3-c3cc(F)c(F)cc3O)cc12
InChIKey: CNKVGRHQVUWEFQ-VWLOTQADSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human FGFR3 using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA
Measurement: IC50 = 27.6 nM (pChEMBL 7.559999942779541)
Descriptors: MW 472.5, ALogP 5.73, HBA 5, HBD 4, PSA 94.06, QED 0.25
Compound (SMILES): O=[N+]([O-])c1ccc(COc2cc3c(cc2OCc2ccc([N+](=O)[O-])cc2)OC2(C=C3)CCOCC2)cc1
InChIKey: LHTNFHWDTHQECR-UHFFFAOYSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00206
Assay: Agonist activity at human TLR4 expressed in HEK293 cells assessed as induction of NF-kB activation-mediated SEAP production after 24 hrs by HTS assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 504.5, ALogP 5.62, HBA 8, HBD 0, PSA 123.2, QED 0.29
Compound (SMILES): COc1ccc(-c2nnc(-c3ccc4nc(-c5c(C)cc(CC(C)(C)C(=O)O)cc5C)[nH]c4c3)o2)cc1
InChIKey: JMHFOGLVAUTEJQ-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: Inhibition of DGAT2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 496.57, ALogP 6.23, HBA 6, HBD 2, PSA 114.13, QED 0.27
Compound (SMILES): CC(=O)c1cccc(-c2nnnn2CCN2CCC(Cc3ccccc3)CC2)c1
InChIKey: DWFZYLFXZNEFKG-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of re-uptake of [3H]-DA at human DAT expressed in HEK293 cells by liquid scintillation counting
Measurement: IC50 = 14600 nM (pChEMBL 4.840000152587891)
Descriptors: MW 389.5, ALogP 3.5, HBA 6, HBD 0, PSA 63.91, QED 0.58
Compound (SMILES): O[C@H]1CC[C@H](Nc2ccc(-c3ccn4c(CC5CC5)nnc4c3Cl)cc2Cl)CC1
InChIKey: SOTRPBHTXCSDMF-WKILWMFISA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Displacement of [3H]-JNJ46281222 from human metabotropic glutamate receptor 2 expressed in CHOK1 cell membranes after 60 mins by microbeta counting analysis
Measurement: Ki = 3.02 nM (pChEMBL 8.520000457763672)
Descriptors: MW 431.37, ALogP 5.37, HBA 5, HBD 2, PSA 62.45, QED 0.57
Compound (SMILES): COCCN1CCc2[nH]c(-c3ccnc(NC4CCOCC4)n3)cc2C1=O
InChIKey: LYRLKFUHEVBCHD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated ERK2 levels
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 371.44, ALogP 1.71, HBA 6, HBD 2, PSA 92.37, QED 0.8
Compound (SMILES): NC(=O)c1cccc(NC(=O)/C=C\C(=O)N2CCC(c3ccc(F)cc3)CC2)c1
InChIKey: HIDGSHNRMYFZHS-HJWRWDBZSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human full length His6-tagged PARP1 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 395.43, ALogP 2.83, HBA 3, HBD 2, PSA 92.5, QED 0.76
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=O)Nc2ccc(I)cc2)c1
InChIKey: WMSZKIBSIKBOMZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 96.4 nM (pChEMBL 7.019999980926514)
Descriptors: MW 417.23, ALogP 2.58, HBA 3, HBD 3, PSA 101.29, QED 0.67
Compound (SMILES): NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC12CC3CC(CC(C3)C1)C2)CP(=O)(O)[C@@H](N)CCc1ccccc1
InChIKey: BUSBNAUESVLLQC-QLOXJZRISA-N
Target: Leucyl-cystinyl aminopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIQ6
Assay: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 565.69, ALogP 4.61, HBA 4, HBD 4, PSA 135.51, QED 0.26
Compound (SMILES): O=C(NCCc1cccnc1)c1cc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)ccc1F
InChIKey: XSLTVZFFDLTMDZ-UNMCSNQZSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Bos taurus
UniProt: P43249
Assay: Inhibition of bovine GRK5 after 5 mins after 5 mins in presence of ATP by phosphorimaging assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 477.54, ALogP 3.69, HBA 6, HBD 2, PSA 81.71, QED 0.52
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H]([C@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N(C)[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](Cc1ccccc1)C(=O)N(C)[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: NYPHFSVDECEUQK-IRLNSCPWSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R LBD expressed in HEK293 cell membranes incubated for 16 to 23 hrs in dark by scintillation proximity assay
Measurement: Ki = 7079.46 nM (pChEMBL 5.150000095367432)
Descriptors: MW 1695.06
Compound (SMILES): COc1cccc2nccc(Nc3cc(-c4cccc(C)n4)ncc3C)c12
InChIKey: WHJWATIXIXBXNQ-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 in human Calu6 cells assessed as reduction in Smad2/3 phosphorylation
Measurement: EC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 356.43, ALogP 5.06, HBA 5, HBD 1, PSA 59.93, QED 0.55
Compound (SMILES): COc1ccc(C(=O)NO)cc1OCc1ccc(Cl)cc1
InChIKey: MQHAQPRTLMGUHC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full length HDAC6 expressed in fall armyworm Sf9 cells using fluorogenic ZMAL as substrate after 90 mins by fluorimetric analysis
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 307.73, ALogP 3.05, HBA 4, HBD 2, PSA 67.79, QED 0.66
Compound (SMILES): CC(=O)Nc1cccc(Nc2ccc3ncc(-c4cccc(Cl)c4)n3n2)c1
InChIKey: AINKQRBPBUTJRM-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant CDK9/cyclin T expressed in insect cells using CDK7/9-tide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 377.84, ALogP 4.75, HBA 5, HBD 2, PSA 71.32, QED 0.54
Compound (SMILES): CCc1cccc(NC(=O)Nc2ccc(-c3ccnc4[nH]nc(C)c34)cc2)c1
InChIKey: MDFHFYALOAZVKP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay
Measurement: IC50 = 1208 nM (pChEMBL 5.920000076293945)
Descriptors: MW 371.44, ALogP 5.14, HBA 3, HBD 3, PSA 82.7, QED 0.46
Compound (SMILES): COc1ccc(C[C@H](NC(=O)c2cccc(=O)[nH]2)C(=O)N[C@@H](Cc2ccccc2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: SSVSAZRGBWOUOO-UXWDXCIHSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of proteasome beta1 in human MOLT4 cell lysate after 1 hr by ELISA
Measurement: IC50 = 91072 nM (pChEMBL 4.039999961853027)
Descriptors: MW 503.56, ALogP 1.81, HBA 6, HBD 3, PSA 129.89, QED 0.34
Compound (SMILES): O=c1[nH]c2ccccc2n1[C@H]1C[C@H](c2nnc(-c3ccncn3)n2-c2ccccc2Cl)C1
InChIKey: PXELYOPIRHQADC-SHTZXODSSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human TNKS2 (873 to 1162 residues) assessed as reduction in NAD+ consumption by fluorescence assay
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 443.9, ALogP 4.14, HBA 7, HBD 1, PSA 94.28, QED 0.45
Compound (SMILES): Cn1c(C#N)ccc1-c1c(Cl)cc(O)cc1Cl
InChIKey: FNYOPUQWXDOSJG-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Androgenic activity at human androgen receptor expressed in African green monkey CV-1 cells assessed as increase in interaction between VP16-fused AR-NTD and GAL4-fused AR-LBD after 17 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 267.12, ALogP 3.58, HBA 3, HBD 1, PSA 48.95, QED 0.86
Compound (SMILES): COc1ccnc(NC2=NC[C@@]3(CN4CCC3CC4)O2)n1
InChIKey: AOXSUYKQQKWOFU-AWEZNQCLSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Agonist activity at alpha4beta2 nAChR (unknown origin) assessed as increase in calcium influx measured for 2 mins by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 289.34, ALogP 0.75, HBA 7, HBD 1, PSA 71.87, QED 0.87
Compound (SMILES): C[C@@H]1CN(c2cccc(C#N)c2)CCN1c1nc(-c2ccncn2)cc(=O)n1C
InChIKey: GBACXGVNHHVFDW-OAHLLOKOSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 387.45, ALogP 1.82, HBA 8, HBD 0, PSA 90.94, QED 0.68
Compound (SMILES): CNS(=O)(=O)c1sc(N(C)C(=O)Cc2ccc(-c3ccccc3)cc2)nc1C
InChIKey: HWKUDWWCPNCBAK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human Carbonic anhydrase 12 assessed as reduction in CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by stopped-flow assay
Measurement: Ki = 57.3 nM (pChEMBL 7.239999771118164)
Descriptors: MW 415.54, ALogP 3.23, HBA 5, HBD 1, PSA 79.37, QED 0.67
Compound (SMILES): CS[C@H]1O[C@@H](c2ccc(C)c(Cc3ccc(CCCC(=O)NC(C)(C)C(=O)NCCN(C)C)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: BNPZTRDIESRGTC-IXYVTWBDSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: In Vitro Human SGLT1 Inhibition Assay: Human sodium/glucose co-transporter type 1 (SGLT1; accession number NP_000334; GI: 4507031) was cloned into pIRESpuro2 vector for mammalian expression (construct: HA-SGLT1-pIRESpuro2). HEK293 cells were transfected with the human HA-SGLT1-pIRESpuro2 vector and the bulk stable cell line was selected in presence of 0.5 μg/mL of puromycin. Human HA-SGLT1 cells were maintained in DMEM media containing 10% FBS, 1% GPS and 0.5 μg/mL of puromycin. The HEK293 cells expressing the human HA-SGLT1 were seeded in 384 well plates (30,000 cells/well) in DMEM media containing 10% FBS, 1% GPS and 0.5 μg/mL of puromycin, then incubated overnight at 37 C, 5% CO2. Cells were then washed with uptake buffer (140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 5 mM Tris, 1 mg/mL bovine serum albumin (BSA), pH 7.3). Twenty microliters of uptake buffer with or without testing compounds were added to the cells. Then, 20 microliters of uptake buffer containing 14C-AMG (100 nCi) were also added to cells. The cell plates were incubated at 37° C., 5% CO2 for 1-2 hours. After washing the cells with uptake buffer, scintillation fluid was added (40 microliters/well) and 14C-AMG uptake was measured by counting radioactivity using a scintillation coulter (TopCoulter NXT; Packard Instruments).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 601.81, ALogP 2.32, HBA 8, HBD 5, PSA 131.36, QED 0.24
Compound (SMILES): O=C(O)CCCCN1C(=O)[C@H](CCC(=O)NC(c2ccccc2)(c2ccccc2)c2ccccc2)N=C(c2ccccc2)c2ccccc21
InChIKey: SXRCWTIPWRYTMS-BHVANESWSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human KDAC6 using FITC-labeled histone H4 acetylated peptide as substrate after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 649.79, ALogP 7.38, HBA 4, HBD 2, PSA 99.07, QED 0.1
Compound (SMILES): CNCc1cccc(CCc2ccc3c(C)cc(N)nc3c2)c1.Cl.Cl
InChIKey: OZIBQKYYCZDPRI-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Mus musculus
UniProt: P29477
Assay: Inhibition of recombinant mouse macrophage iNOS expressed in Escherichia coli assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of 10 uM H4B by hemoglobin capture assay
Measurement: Ki = 4540 nM (pChEMBL 5.340000152587891)
Descriptors: MW 305.43, ALogP 3.63, HBA 3, HBD 2, PSA 50.94, QED 0.76
Compound (SMILES): Cc1ccc(Oc2ccc(-c3ccn4c(CC5CC5)nnc4c3Cl)cc2Cl)c(C)n1
InChIKey: IRTCOFQSEANRBE-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Displacement of [3H]-JNJ46281222 from human metabotropic glutamate receptor 2 expressed in CHOK1 cell membranes after 60 mins by microbeta counting analysis
Measurement: Ki = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 439.35, ALogP 6.46, HBA 5, HBD 0, PSA 52.31, QED 0.36
Compound (SMILES): Nc1nccn2c1c(-c1ccc(C(=O)Nc3cc(C(F)(F)F)ccn3)cc1)nc2[C@H]1CC[C@@H](C(=O)O)CC1
InChIKey: YZLMBXMJXHFDPM-WOVMCDHWSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Btk Enzyme Activity Assay: BTK enzymatic activity was determined with the LANCE (Lanthanide Chelate Excite) TR-FRET (Time-resolved fluorescence resonance energy transfer) assay. In this assay, the potency (IC50) of each compound was determined from an eleven point (1:3 serial dilution; final compound concentration range in assay from 1 μM to 0.017 nM) titration curve using the following outlined procedure. To each well of a black non-binding surface Corning 384-well microplate (Corning Catalog #3820), 5 nL of compound (2000 fold dilution in final assay volume of 10 μL) was dispensed, followed by the addition of 7.5 μL of 1× kinase buffer (50 mM Hepes 7.5, 10 mM MgCl2, 0.01% Brij-35, 1 mM EGTA, 0.05% BSA & 1 mM DTT) containing 5.09 pg/μL (66.67 pM) of BTK enzyme (recombinant protein from baculovirus-transfected Sf9 cells: full-length BTK, 6HIS-tag cleaved). Following a 60 minute compound & enzyme incubation, each reaction was initiated by the addition of 2.5 μL 1× kinase buffer containing 8 μM biotinylated A5 peptide (Biotin-EQEDEPEGDYFEWLE-NH2) (SEQ.ID.NO.: 1), and 100 μM ATP. The final reaction in each well of 10 μL consists of 50 pM hBTK, 2 μM biotin-A5-peptide, and 25 μM ATP. Phosphorylation reactions were allowed to proceed for 120 minutes. Reactions were immediately quenched by the addition of 20 uL of 1× quench buffer (15 mM EDTA, 25 mM Hepes 7.3, and 0.1% Triton X-100) containing detection reagents (0.626 nM of LANCE-Eu-W1024-anti-phosphoTyrosine antibody, PerkinElmer and 86.8 nM of Streptavidin-conjugated Dylight 650, Dyomics/ThermoFisher Scientific). After 60 minutes incubation with detection reagents, reaction plates were read on a PerkinElmer EnVision plate reader using standard TR-FRET protocol. Briefly, excitation of donor molecules (Eu-chelate:anti-phospho-antibody) with a laser light source at 337 nm produces energy that can be transferred to Dylight-650 acceptor molecules if this donor:acceptor pair is within close proximity Fluorescence intensity at both 665 nm (acceptor) and 615 nm (donor) are measured and a TR-FRET ratio calculated for each well (acceptor intensity/donor intensity). IC50 values were determined by 4 parameter robust fit of TR-FRET ratio values vs. (Log10)) compound concentrations.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 524.5, ALogP 5, HBA 7, HBD 3, PSA 135.5, QED 0.33
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1Cc2cn(nn2)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2cnc[nH]2)C(=O)N1)C(=O)O
InChIKey: BJVBJLDUSIFIEH-URAFIAKLSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at EYFP-fused human MC5R expressed in HEK293 cells after 16 to 20 hrs by CRE-driven reporter assay
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 1111.3
Compound (SMILES): Cc1ccc(F)c(NC(=O)Nc2ccc(-c3ccnc4[nH]nc(C)c34)cc2)c1
InChIKey: YMJXEFAHWSSFMT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay
Measurement: IC50 = 4293 nM (pChEMBL 5.369999885559082)
Descriptors: MW 375.41, ALogP 5.02, HBA 3, HBD 3, PSA 82.7, QED 0.47
Compound (SMILES): Cc1cc([C@@H]2CN(C(=O)c3ccc(F)c(Br)c3)CC(F)(F)C2)n2ncnc2n1
InChIKey: TTWAYHJJEHLVNR-LBPRGKRZSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of PDE3A (unknown origin) using FAM-labeled cAMP as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by IMAP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.25, ALogP 3.6, HBA 5, HBD 0, PSA 63.39, QED 0.59
Compound (SMILES): Cc1n[nH]c2nccc(-c3ccc(NC(=O)NCCCCc4ccccc4)cc3)c12
InChIKey: NXWOTWQLSTXDFR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay
Measurement: IC50 = 10917 nM (pChEMBL 4.960000038146973)
Descriptors: MW 399.5, ALogP 5.08, HBA 3, HBD 3, PSA 82.7, QED 0.38
Compound (SMILES): CCCCCCNC(=O)Nc1ccc(-c2ccnc3[nH]nc(C)c23)cc1
InChIKey: JYSCRDCBJSBWKB-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of PDGFRalpha (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 351.45, ALogP 4.64, HBA 3, HBD 3, PSA 82.7, QED 0.54
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3ccccc23)c(OC)cc1N(C)CCN(C)C
InChIKey: FHJIFWIXZSYZDF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type human N-terminal GST-tagged EGFR cytoplasmic domain (669 to 1210 end amino acid residues) expressed in baculovirus expression system using TK peptide substrate preincubated with enzyme for 30 mins followed by substrate addition measured after 25 mins by HTRF assay
Measurement: IC50 = 9272 nM (pChEMBL 5.03000020980835)
Descriptors: MW 408.51, ALogP 3.44, HBA 6, HBD 3, PSA 85.52, QED 0.47
Compound (SMILES): CN1C2CCC1[C@@H](c1cc(-c3ccccc3)no1)[C@@H](OC(c1ccc(F)cc1)c1ccc(F)cc1)C2
InChIKey: XOVAXDRXQONSIA-WKYFEGLOSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from Sprague-Dawley rat brain SERT after 60 mins by liquid scintillation counting method
Measurement: Ki = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 486.56, ALogP 6.74, HBA 4, HBD 0, PSA 38.5, QED 0.3
Compound (SMILES): Cc1ccccc1-c1nnc(Cc2nc3ccccc3[nH]2)o1
InChIKey: XIEDBRMNHVILCQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGF induced EGFR phosphorylation in human KB cells preincubated for 90 mins followed by EGF addition for 5 mins by sandwich ELISA method
Measurement: IC50 = 39719.15 nM (pChEMBL 4.400000095367432)
Descriptors: MW 290.33, ALogP 3.51, HBA 4, HBD 1, PSA 67.6, QED 0.63
Compound (SMILES): Cc1cc(COc2ccc3c(c2)NCCN([C@H](C)C(=O)NO)S3)cc(C)n1
InChIKey: SNVUTAYIIANZNZ-CQSZACIVSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Sus scrofa
UniProt: O77636
Assay: Inhibition of porcine spleen TACE using Mca-Pro-LeuAla-Gln-Ala-Val-Dpa-Arg-Ser-Ser-Ser-Agr-NH2 as substrate by fluorescence assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 388.49, ALogP 2.91, HBA 7, HBD 3, PSA 86.72, QED 0.41
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: BNIKUQVBVMIHAO-SQYYYKBQSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of biotinylated K-Ras G12D mutant (unknown origin) assessed as reduction in SOS1 (564 to 1049 residues)-mediated BODIPY-GDP-GTP exchange after 1 hr by TR-FRET assay
Measurement: IC50 = 15400 nM (pChEMBL 4.809999942779541)
Descriptors: MW 2517.05
Compound (SMILES): CN1CN2Cc3c(c4ccccc4n3Cc3ccc(C(=O)NO)cc3)C(C2)C1=O
InChIKey: ZNIMBGDYTMHQRA-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length recombinant human C-terminal GST-tagged HDAC2 expressed in baculovirus-infected insect cells using RHKK(Ac)AMC as substrate after 60 mins by fluorimeter
Measurement: Ki = 1356 nM (pChEMBL 5.869999885559082)
Descriptors: MW 390.44, ALogP 2.14, HBA 5, HBD 2, PSA 77.81, QED 0.53
Compound (SMILES): Cc1c(C(=O)N2CCN(c3ccccc3)CC2)nc2ccc(Cl)cc2c1O
InChIKey: LHULJLLNFWPBMG-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin) using linoleic acid as substrate preincubated for 5 mins followed by substrate addition by spectrophotometric assay
Measurement: IC50 = 5910 nM (pChEMBL 5.230000019073486)
Descriptors: MW 381.86, ALogP 3.86, HBA 4, HBD 1, PSA 56.67, QED 0.73
Compound (SMILES): O=C(CCCNC(=O)C[C@@H]1N=C(c2ccccc2)c2ccccc2NC1=O)NO
InChIKey: AGMXQXJRIFEMDX-KRWDZBQOSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human KDAC6 using FITC-labeled histone H4 acetylated peptide as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 1760 nM (pChEMBL 5.75)
Descriptors: MW 394.43, ALogP 1.64, HBA 5, HBD 4, PSA 119.89, QED 0.32
Compound (SMILES): C[C@]1(C(=O)O)CCC[C@@](C)(c2nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c3c(N)nccn23)C1
InChIKey: TUABCARNQAPXIP-SXOMAYOGSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 552.56, ALogP 5.57, HBA 7, HBD 3, PSA 135.5, QED 0.29
Compound (SMILES): Cc1cc(C)cc(S(=O)(=O)c2c(C(=O)N[C@@H](C)C(=O)NCc3ccncc3)[nH]c3ccc(Cl)cc23)c1
InChIKey: YTEIENLXHBJENY-KRWDZBQOSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase p66 Y181I mutant associated RNA dependent DNA polymerase activity expressed in Escherichia coli assessed as reduction in [3H]dTTP incorporation using poly(rA)/oligo(dT) as template/primer by scintillation counting analysis
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 525.03, ALogP 4.1, HBA 5, HBD 3, PSA 121.02, QED 0.34
Compound (SMILES): CCc1cc(O)ccc1-c1ccc2c(C(=O)N(C)C)n[nH]c2c1
InChIKey: VNWQTNWVEAPHGJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of GST tagged human recombinant JAK3 catalytic domain expressed in baculovirus using peptide substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by microfluidic assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 309.37, ALogP 3.2, HBA 3, HBD 2, PSA 69.22, QED 0.78
Compound (SMILES): Cn1cc(-c2ccncc2CCC(=O)Nc2ccc(CN3CCOCC3)cc2)cn1
InChIKey: RTIFRQDVZMGONB-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 in human SW480 cells assessed as reduction in IFN-gamma induced STAT1 phosphorylation at Ser727 residues preincubated for 2 hrs followed by IFN-gamma addition measured after 1 hr by In-cell western assay
Measurement: EC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 405.5, ALogP 2.89, HBA 6, HBD 1, PSA 72.28, QED 0.65
Compound (SMILES): CN1C(=O)[C@@H]2CN(S(=O)(=O)c3ccc4occc4c3)C[C@@H]2c2cnccc21
InChIKey: QODWZTUPLVMSQR-HZPDHXFCSA-N
Target: Glycine receptor (alpha-1/beta) (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Positive allosteric modulation of human glycine alpha1beta receptor expressed in HEK293T cells assessed as glycine-induced increase in current response after 18 to 24 hrs by membrane potential blue dye based FLIPR assay
Measurement: EC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 383.43, ALogP 2.21, HBA 5, HBD 0, PSA 83.72, QED 0.68