lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1nc(N/N=C/c2cccc(OCc3ccccc3)c2)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
InChIKey: PVQRGONOKPAAHU-VJRCLNGSSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]CGS21680 from human cloned adenosine receptor A2A expressed in HEK-293 cell membrane incubated for 60 mins by microbeta counting method
Measurement: Ki = 173 nM (pChEMBL 6.760000228881836)
Descriptors: MW 491.51, ALogP 1.04, HBA 12, HBD 5, PSA 173.16, QED 0.18
Compound (SMILES): C#CCSc1nc(-c2cc(OC)c(OC)c(OC)c2)c(C#N)c(N2CCCCC2)n1
InChIKey: JTXNQGFYWXLMLJ-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Binding affinity to N-terminal GST tagged recombinant human DCN1 (58 to 259 residues) expressed in Escherichia coli BL21(DE3) assessed as reduction in DCN1-FAM-labelled N-terminal acetylated UBE2M (1 to 21 residues) protein-protein interaction after 30 mins by HTRF assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 424.53, ALogP 3.76, HBA 8, HBD 0, PSA 80.5, QED 0.38
Compound (SMILES): O=C(c1cc(-c2ccc(=O)[nH]c2)on1)N1CCC(Cc2ccc(F)cc2)CC1
InChIKey: AYQJOJFEPWZCRH-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, NMDA 2B (SINGLE PROTEIN), Mus musculus
UniProt: Q01097
Assay: Antagonist activity at mouse NR2B receptor expressed in HEK293 cells co-expressing NR1 subunit assessed as reduction in glutamic acid/glycine-induced calcium ion influx by fluorescence based assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 381.41, ALogP 3.26, HBA 4, HBD 1, PSA 79.2, QED 0.75
Compound (SMILES): O=C1NC(=O)C(c2c[nH]c3ccccc23)=C1c1cc(N2CCN(C(=O)CCl)CC2)ccc1C(F)(F)F
InChIKey: WKENHJFHQNXSMC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 1 mM ATP by HTRF assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 516.91, ALogP 3.64, HBA 4, HBD 2, PSA 85.51, QED 0.41
Compound (SMILES): CC(C)Nc1cc(COc2ccccc2CC(=O)O)cc(-c2cccc([C@H](N)CO)c2)c1
InChIKey: RYXYOJVPYQZGGE-XMMPIXPASA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of FD-mediated alternative complementation pathway in 50% human whole blood assessed as reduction in zymosan-induced membrane-attack complex formation preincubated for 15 mins followed by zymosan stimulation and measured after 40 mins by ELISA
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 434.54, ALogP 4.37, HBA 5, HBD 4, PSA 104.81, QED 0.38
Compound (SMILES): Cn1cc(-c2cccc(C(=O)N[C@@H]3CCN(C#N)C3)c2F)cn1
InChIKey: MQAYVICWIVHQHM-GFCCVEGCSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 313.34, ALogP 1.51, HBA 5, HBD 1, PSA 73.95, QED 0.87
Compound (SMILES): CNC[C@@H](O)CN1CCc2c(cccc2OCc2ccc(-c3nccs3)cc2)C1
InChIKey: YOIPDYXMOWADRA-HXUWFJFHSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Inhibition of PRMT1 (unknown origin) preincubated for 15 mins followed by substrate addition and measured after 60 mins by AlphaLisa assay
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 409.56, ALogP 3.33, HBA 6, HBD 2, PSA 57.62, QED 0.6
Compound (SMILES): CCc1nc(C)c(C(=O)Nc2ccc(-c3ccc(C45CCC(CC(=O)O)(CC4)OC5)cc3)cc2)o1
InChIKey: WDOFVORFQCWUDU-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z2A7
Assay: Inhibition of DGAT1 in mouse C2C12 cells assessed as reduction in intracellular triglyceride production incubated for 2 hrs in presence of BSA-complexed oleate by LC/MS/MS analysis
Measurement: EC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 474.56, ALogP 5.52, HBA 5, HBD 2, PSA 101.66, QED 0.47
Compound (SMILES): O=C1COc2ccc(C(=O)N3c4ccc(Cl)cc4C[C@@H]3CCO)cc2N1
InChIKey: RNFNFRANQNBNSW-AWEZNQCLSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Binding affinity to recombinant human GR LBD by fluormone GS red-fluorescence polarization assay
Measurement: Ki > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 372.81, ALogP 2.62, HBA 4, HBD 2, PSA 78.87, QED 0.87
Compound (SMILES): Cc1ccc2c(c1)nc(Cn1nnc3ccccc31)n2CCN(C)C
InChIKey: RVPAQRWGBZXHFG-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membranes measured after 90 mins
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 334.43, ALogP 2.7, HBA 6, HBD 0, PSA 51.77, QED 0.56
Compound (SMILES): NCCCNCCCCNCCCNC(=O)[C@H](CC1CCCCC1)NC(=O)C1CCCC1
InChIKey: HCVVQYDWEUQYOH-QHCPKHFHSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Antagonist activity at alpha4beta2 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay
Measurement: IC50 = 5.43 nM (pChEMBL 8.270000457763672)
Descriptors: MW 451.7, ALogP 2.45, HBA 5, HBD 5, PSA 108.28, QED 0.22
Compound (SMILES): O=C(NCc1cc(F)cc(Cl)c1)[C@@]1(O)CCN(c2ccc3[nH]ccc3c2)C1=O
InChIKey: YPBBCOGVFKOTTG-FQEVSTJZSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of MetAP2 in HUVEC assessed as reduction in viability incubated for 3 days by CyQUANT Direct Cell proliferation assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 401.83, ALogP 2.74, HBA 3, HBD 3, PSA 85.43, QED 0.59
Compound (SMILES): Cc1ccccc1NC(=O)Nc1nnc(SCc2cc(=O)n3ccccc3n2)s1
InChIKey: VWPDJVRLHVUTDM-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human full length TRKB expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 424.51, ALogP 3.79, HBA 8, HBD 2, PSA 101.28, QED 0.37
Compound (SMILES): Cc1ccc(N2CCN(C(=O)CSCc3c(C)noc3C)CC2)cc1
InChIKey: ADDBMVAFDVHRAU-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 359.5, ALogP 3.18, HBA 5, HBD 0, PSA 49.58, QED 0.82
Compound (SMILES): CCN(CCCCNC(=O)c1cc(O)c(C(=O)NCCCCN(CC)Cc2ccc(N(C)C)cc2)cc1O)Cc1ccc(N(C)C)cc1
InChIKey: NRWUSPBIPBJDMB-UHFFFAOYSA-N
Target: Butyrylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JKC1
Assay: Inhibition of rat serum BuChE using butyrylthiocholine iodide as substrate after 15 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 660.9, ALogP 5.29, HBA 8, HBD 4, PSA 111.62, QED 0.1
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C(=N)N)C5)ncc3F)cc2n1C(C)C
InChIKey: CEIAWFVLEUQXHI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 534.62, ALogP 3.98, HBA 8, HBD 3, PSA 124.87, QED 0.24
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)c1nc2ccccc2s1
InChIKey: MZLDHCSWGXPGJS-DQEYMECFSA-N
Target: Serine protease hepsin (SINGLE PROTEIN), Homo sapiens
UniProt: P05981
Assay: Inhibition of recombinant human C-terminal His10-tagged hepsin catalytic domain preincubated for 30 mins followed by Boc-QAR-AMC substrate addition and measured for 1 hr by fluorescence assay
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 627.73, ALogP 3.01, HBA 8, HBD 6, PSA 202.38, QED 0.06
Compound (SMILES): NC(=S)n1nc(-c2ccc(Cl)cc2)cc1-c1cn(-c2ccccc2)nc1-c1ccc(OCc2ccccc2)cc1
InChIKey: IVEOOKGWXNSUAG-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX1 assessed as decrease in prostaglandin production using arachidonic acid as substrate pretreated for 15 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 = 6070 nM (pChEMBL 5.21999979019165)
Descriptors: MW 562.1, ALogP 7.39, HBA 6, HBD 1, PSA 70.89, QED 0.21
Compound (SMILES): Cc1nc(N)nc(N[C@@H](C)c2c(-c3ccccc3)c(=O)n3cc(F)ccc3c2-c2ccc(F)cc2)c1C#N
InChIKey: OACRRIRKPJAVFE-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 508.53, ALogP 5.64, HBA 7, HBD 2, PSA 109.1, QED 0.32
Compound (SMILES): C=CC(=O)N1CC(Oc2c(N)ncnc2-c2cc(F)cc(NC(=O)c3ccc(C(C)(C)O)c(F)c3F)c2C)C1
InChIKey: HKYGGVCUSXGWRZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in vitamin D3 differentiated human THP1 cells assessed as inhibition of FCgammaR-induced IL8 production measured after 24 hrs by HTRF assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 541.53, ALogP 3.71, HBA 7, HBD 3, PSA 130.67, QED 0.39
Compound (SMILES): O=C(CCCN1CCC(O)(c2ccc(Cl)cc2)CC1)c1ccc(F)c(F)c1
InChIKey: HNLPCBJRLMCWJQ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of PPHT-red from SNAP-tagged human D2LR expressed in CHOK1 cell membranes by TR-FRET assay
Measurement: Ki = 7.762 nM (pChEMBL 8.109999656677246)
Descriptors: MW 393.86, ALogP 4.56, HBA 3, HBD 1, PSA 40.54, QED 0.73
Compound (SMILES): O=C(c1ccc(-c2cncc(F)c2)s1)c1cc(F)c(F)c(O)c1F
InChIKey: WZBORHFEYHAKDC-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 353.3, ALogP 4.3, HBA 4, HBD 1, PSA 50.19, QED 0.43
Compound (SMILES): O=C(Nc1ccc(Oc2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1)c1c(F)cccc1OC(F)(F)F
InChIKey: TZWVRQYEZNQBPM-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Inhibition of human TLR7 expressed in HEK293 cells assessed as reduction in R848-induced NFkappaB production incubated for 16 hrs by quanti-blue SEAP assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 527.31, ALogP 7.81, HBA 3, HBD 1, PSA 47.56, QED 0.34
Compound (SMILES): O=c1c2ccccc2sn1NCc1ccccc1
InChIKey: WCFGJULPEWYMOV-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8R431
Assay: Inhibition of recombinant rat MGL C208A mutant expressed in human HeLa cells using 2-oleoylglycerol as substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins by LC-MS analysis
Measurement: IC50 = 44.9 nM (pChEMBL 7.349999904632568)
Descriptors: MW 256.33, ALogP 2.81, HBA 4, HBD 1, PSA 34.03, QED 0.78
Compound (SMILES): C[C@H](O)[C@H](CO)Nc1c(C(N)=O)cnn2cc(-c3ccccc3)cc12
InChIKey: PRWQQLFMBINSAW-NHYWBVRUSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-tagged JAK1 (unknown origin) using fluoresceinated peptide as substrate measured after 3 hrs by electrophoresis method
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 340.38, ALogP 1.25, HBA 6, HBD 4, PSA 112.88, QED 0.54
Compound (SMILES): Cc1ccc2nc([C@@H](CC3CCN(C(=O)C(C)C)CC3)N3C(=O)CN(c4ccc(Oc5ccccc5)cc4)C3=O)n(C)c2c1
InChIKey: VZAVDSHZLZPBFD-WJOKGBTCSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Antagonist activity at human FXR expressed in Huh7 cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrs
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 593.73, ALogP 6.47, HBA 6, HBD 0, PSA 87.98, QED 0.22
Compound (SMILES): COc1ccccc1N1CCN(CCCNC(=O)NN(Cc2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: BSICDIBRXJYNPB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H] Spiperone from human D2S receptor expressed in CHO cells by competitive radioligand binding assay
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 509.6, ALogP 4.41, HBA 5, HBD 2, PSA 60.08, QED 0.31
Compound (SMILES): C[C@]1(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)N=C(N)SC[C@H]1c1ccccc1
InChIKey: BCDWEYSMCDBNJS-GAJHUEQPSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) using Mca-APP Swedish Lys-Met/Asn-Leu mutant-Dnp quencher as substrate by fluorescence assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 469.52, ALogP 4.23, HBA 7, HBD 2, PSA 102.49, QED 0.56
Compound (SMILES): Cc1cc(-c2ccc(CC(=O)Nc3ccc(-c4ccccc4)cn3)cn2)ccn1
InChIKey: OZRNKXFMUVNVFC-UHFFFAOYSA-N
Target: Protein Wnt-3a (SINGLE PROTEIN), Homo sapiens
UniProt: P56704
Assay: Wnt-Luc Reporter Assay: Human embryonic kidney 293 cells (obtained from American Type Culture Collection, ATCC, Manassas, Va.) are cultured in DMEM medium (Gibco/Invitrogen, Carlsbad, Calif.) supplemented with 10% FBS (Gibco/Invitrogen, Carlsbad, Calif.), 50 unit/mL penicillin and 50 μg/mL of streptomycin (Gibco/Invitrogen, Carlsbad, Calif.) at 37° C. with 5% CO2 in air atmosphere. 293 cells in a 10 cm dish are co-transfected with 8 μg of STF-reporter plasmid containing a luciferase gene driven by Wnt-responsive elements and 2 μg of pcDNA3.1-Neo (Gibco/Invitrogen, Carlsbad, Calif.) with 30 μL of FuGENE6 (Roche Diagnostics, Indianapolis, Ind.) following the manufacturer's protocol. Stable cell lines (293 Wnt-Luc) were selected with 400 μg/mL of G418 (Gibco/Invitrogen, Carlsbad, Calif.). The 293 Wnt-Luc cells and L-cell Wnt3a cells (obtained from American Type Culture Collection, ATCC, Manassas, Va.) are trypsinized and co-cultured into a 384-well plate with DMEM medium supplemented with 2% FBS, and treated with different concentrations of a compound of the invention. After 24 hours, the firefly luciferase activities are assayed with the Bright-Glo Luciferase Assay System (Promega, Madison, Wis.). The IC50 is measured when the effect of the compound reduces the luminescence signal by 50%.
Measurement: IC50 < 0.14 nM (pChEMBL 9.854000091552734)
Descriptors: MW 380.45, ALogP 4.7, HBA 4, HBD 1, PSA 67.77, QED 0.55
Compound (SMILES): CCCCc1nc(Cl)c(CNC(=O)[C@H](CS)CC(C)C)n1Cc1ccc(-c2ccccc2C(=O)O)cc1
InChIKey: XRWGWRHXWJHKMY-QFIPXVFZSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: Inhibition of NEP (unknown origin) preincubated for 10 mins followed by fluorogenic substrate addition and measured after 20 mins by fluorescence assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 542.15, ALogP 6.5, HBA 5, HBD 3, PSA 84.22, QED 0.22
Compound (SMILES): CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)c1cn(CC)nc1-2
InChIKey: YDSPBMVKWIIBIS-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human CB2 receptor expressed in HEK293 cell membranes after 90 mins by liquid scintillation counting method
Measurement: Ki > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 370.54, ALogP 6.15, HBA 4, HBD 1, PSA 47.28, QED 0.59
Compound (SMILES): O=c1[nH]c2cnc(-c3cnc4ccc(F)cn34)nc2n1C1CCOCC1
InChIKey: NTFXSLRFNIPLJJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human N-terminal His-tagged JAK2 (826 to 1132 residues) expressed in baculovirus expression system using PolyGT-Biotin as substrate measured after 3 to 20 hrs by HTRF assay
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 354.35, ALogP 1.92, HBA 7, HBD 1, PSA 90.1, QED 0.59
Compound (SMILES): O=C(O)COc1ccc(OCc2nc(-c3ccccc3)cs2)cc1F
InChIKey: BSZHZUTYJJTQEU-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 receptor expressed in CHO cells by Fluo 4-AM dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.38, ALogP 3.99, HBA 5, HBD 1, PSA 68.65, QED 0.69
Compound (SMILES): Fc1ccc(CCNCc2ccc(Oc3ccccc3)cc2)cc1
InChIKey: BPPBYUPUAFZCNN-UHFFFAOYSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of (His)6 tagged human recombinant LTA4H expressed in Escherichia coli BL21(DE3) using non-fluorescent L-arginine-7-amino-4-methylcoumarine as substrate preincubated for 30 mins followed by substrate addition and measured for 30 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 321.39, ALogP 4.95, HBA 2, HBD 1, PSA 21.26, QED 0.62
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)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](Cc1cnc[nH]1)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: VRVNFWDNZGEBHE-CZVJXMOHSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.012 nM (pChEMBL 10.920000076293945)
Descriptors: MW 3657.14
Compound (SMILES): C=CC(=O)N[C@H]1CCCN(c2ccc(C(F)(F)F)c(C3=C(c4c[nH]c5ccccc45)C(=O)NC3=O)c2)C1
InChIKey: STCBITIZMNQJLU-HNNXBMFYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 1 mM ATP by HTRF assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 508.5, ALogP 4.02, HBA 4, HBD 3, PSA 94.3, QED 0.36
Compound (SMILES): CC(C)Cc1cc2c(cc1F)OC[C@H](CS(N)(=O)=O)N2C(=O)c1ccc2c(c1)NC(=O)CO2
InChIKey: NREZDYQUMMSPNC-OAHLLOKOSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Binding affinity to recombinant human GR LBD by fluormone GS red-fluorescence polarization assay
Measurement: Ki = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 477.51, ALogP 2.05, HBA 6, HBD 2, PSA 128.03, QED 0.68
Compound (SMILES): CC(C)Cc1cc(CNC(=O)C2C3CN(C(=O)c4ccccc4)CC32)nn1-c1ccccc1
InChIKey: AJDSKTXYDMITDW-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of T-type alpha1H channel (unknown origin) by whole cell patch clamp method
Measurement: IC50 = 2890 nM (pChEMBL 5.539999961853027)
Descriptors: MW 442.56, ALogP 3.71, HBA 4, HBD 1, PSA 67.23, QED 0.61
Compound (SMILES): CCN(CC)CCn1c(Cc2ccc(Cl)cc2)nc2cc(C(C)=O)ccc21
InChIKey: FIJCSQMRNIRDOO-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membranes measured after 90 mins
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 383.92, ALogP 4.82, HBA 4, HBD 0, PSA 38.13, QED 0.52
Compound (SMILES): Fc1ccc2c(c1)C1=NCCCN1C(=S)S2
InChIKey: ONKSFHXYNMMECZ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC2 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 252.34, ALogP 2.67, HBA 3, HBD 0, PSA 15.6, QED 0.66
Compound (SMILES): COc1cc(CCNC[C@@H](O)COc2cccc3ccccc23)ccc1OCCSSCCN
InChIKey: ZBAVHTZBLFYIAR-JOCHJYFZSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Mus musculus
UniProt: P34971
Assay: Displacement of [3H]CGP12177 from mouse beta1 adrenoceptor expressed in HEK293T cell membranes
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 502.7, ALogP 4.14, HBA 8, HBD 3, PSA 85.97, QED 0.2
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(P(=O)(O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccccc1OC(=O)N(C)C
InChIKey: IDIAOYLIGRSJIR-IXCJQBJRSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 744.74, ALogP 4.22, HBA 10, HBD 4, PSA 214.25, QED 0.04
Compound (SMILES): NS(=O)(=O)NCc1nnc(C(=O)c2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: LXSODRTWQNWTOG-UHFFFAOYSA-N
Target: Hepatic triacylglycerol lipase (SINGLE PROTEIN), Homo sapiens
UniProt: P11150
Assay: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 415.46, ALogP 1.87, HBA 8, HBD 2, PSA 141.07, QED 0.46
Compound (SMILES): Nc1ccc2oc(N3CCCCC3)nc2c1
InChIKey: HUBLYOMFVGUXJJ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition and measured for 1 min by DTNB reagent-based spectrophotometric analysis
Measurement: IC50 = 24212 nM (pChEMBL 4.619999885559082)
Descriptors: MW 217.27, ALogP 2.4, HBA 4, HBD 1, PSA 55.29, QED 0.75
Compound (SMILES): Cc1nn(-c2ccccc2)c2c1C(/C=C/c1cccc(C#N)c1)CS(=O)(=O)O2
InChIKey: VOUNLHMMTHEDPL-ZHACJKMWSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 10630 nM (pChEMBL 4.96999979019165)
Descriptors: MW 391.45, ALogP 3.57, HBA 6, HBD 0, PSA 84.98, QED 0.64
Compound (SMILES): COc1ccccc1N1CCN(CCNC(=O)/N=N/c2ccc(F)cc2)CC1
InChIKey: OTKMHDVPFOECAQ-WCWDXBQESA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H] Spiperone from human D2S receptor expressed in CHO cells by competitive radioligand binding assay
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 385.44, ALogP 3.45, HBA 5, HBD 1, PSA 69.53, QED 0.77
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)[C@@H](C)O
InChIKey: QJNTXRSPVHTKDD-KXBPRMRFSA-N
Target: Dickkopf-related protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O94907
Assay: Inhibition of biotin-labeled human recombinant DKK1 assessed as reduction in DKK1 interaction with LRP-6/Fc incubated overnight by chemiluminescence based Alpha-screen assay
Measurement: IC50 <= 1 nM (pChEMBL 9)
Descriptors: MW 4748.29
Compound (SMILES): CC(C)N(C)[C@@H]1CC[C@H](N2CC[C@H](NC(=O)c3cccc(C(F)(F)F)c3)C2=O)[C@H](NS(C)(=O)=O)C1
InChIKey: KCGHNEUWTNNXMF-WCIQWLHISA-N
Target: C-C chemokine receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51681
Assay: Antagonist activity at CCR5 (unknown origin) expressed in human HT1080 cells assessed as blockade of MIP1beta-binding to receptor
Measurement: IC50 = 3469 nM (pChEMBL 5.460000038146973)
Descriptors: MW 518.6, ALogP 2.22, HBA 5, HBD 2, PSA 98.82, QED 0.58
Compound (SMILES): Nc1ncnc2c3c(n(-c4ccc(CC(=O)Nc5ccc(Cl)c(Cl)c5)cc4)c12)CCC3
InChIKey: SEPXWCACIOXTBL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Displacement of kinase tracer 236 from recombinant human His-tagged KDR cytoplasmic domain (789 to 1356 residues) expressed in baculovirus-infected insect cells measured after 5 hrs by TR-FRET based LanthaScreen assay
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 452.35, ALogP 4.98, HBA 5, HBD 2, PSA 85.83, QED 0.46
Compound (SMILES): CN(C)S(=O)(=O)c1cccc(-c2ccn(C/C(F)=C/CN)c2)c1.Cl
InChIKey: DBKSDTZAAGBNNW-PSUINESXSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P33072
Assay: Inhibition of LOX in bovine aorta using putrescine as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every 2.5 mins for 30 mins by Amplex-Red oxidation assay
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 337.42, ALogP 2.22, HBA 4, HBD 1, PSA 68.33, QED 0.88
Compound (SMILES): O=C(NCc1cccc2c1OCCCO2)c1ccc(-c2ccncc2)cc1
InChIKey: ZNHSSCHACDGIFB-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of GST-fused human recombinant ROCK2 (11 to 552 residues) expressed in Spodoptera frugiperda insect cells using STK S2 peptide substrate and 33P-ATP after 60 mins by HTRF assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 360.41, ALogP 3.84, HBA 4, HBD 1, PSA 60.45, QED 0.77
Compound (SMILES): O=C(O)c1cc(SCCc2ccccc2)ccc1NS(=O)(=O)c1ccc(-c2ccccc2)nc1
InChIKey: YJAFEZNEDQWNIO-UHFFFAOYSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Inhibition of N-terminal His6-tagged human Bfl-1 (1 to 151 residues), expressed in Escherichia coli Rosetta2 DE3 by fluorescent labeled FAM-Bid peptide based fluorescence polarization assay
Measurement: Ki = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 490.61, ALogP 5.58, HBA 5, HBD 2, PSA 96.36, QED 0.3
Compound (SMILES): Cn1cc(NC(=O)[C@@H]2CCCC[C@H]2C(=O)c2ccc(-c3cc[nH]n3)cc2)c(C(F)(F)F)n1
InChIKey: VAHNFOCNMLUUOJ-HZPDHXFCSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in human whole blood assessed as reduction in calcium ionophore-stimulated LTB4 production preincubated for 30 mins followed by calcium ionophore stimulation and measured after 20 mins by EIA
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 445.45, ALogP 4.46, HBA 5, HBD 2, PSA 92.67, QED 0.57
Compound (SMILES): CCCn1c(SCc2cccc(C)c2)nc2c1c(=O)[nH]c(=O)n2C
InChIKey: ZSDNYHJVSOHTPD-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin)
Measurement: IC50 = 96870 nM (pChEMBL 4.010000228881836)
Descriptors: MW 344.44, ALogP 2.43, HBA 6, HBD 1, PSA 72.68, QED 0.72
Compound (SMILES): COc1ccc(-c2ccc3ncc(-c4nnco4)c(NCCCN4CCOCC4)c3c2)cc1
InChIKey: HOHLTWPTYNTYRD-UHFFFAOYSA-N
Target: DNA topoisomerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11387
Assay: Poison activity at TOP1 in human MCF7 cells assessed as decrease in relaxed supercoiled pBS(SK+) DNA mobility measured after 30 mins by ethidium bromide staining based agarose gel electrophoresis
Measurement: IC50 = 2510 nM (pChEMBL 5.599999904632568)
Descriptors: MW 445.52, ALogP 4.09, HBA 8, HBD 1, PSA 85.54, QED 0.41
Compound (SMILES): CC(=O)c1ccc(OCCCCCCCCCN2CCc3ccccc3C2)cc1O
InChIKey: XCLGEGMPSPFEPW-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide incubated for 15 mins as substrate by Ellman's method
Measurement: IC50 = 11600 nM (pChEMBL 4.940000057220459)
Descriptors: MW 409.57, ALogP 5.76, HBA 4, HBD 1, PSA 49.77, QED 0.36
Compound (SMILES): O=C(C1CCN(C(=O)C(F)(F)F)CC1)N1N=CCC1c1ccccc1
InChIKey: IIVRDQFOCAQQAZ-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 353.34, ALogP 2.75, HBA 3, HBD 0, PSA 52.98, QED 0.82
Compound (SMILES): CS(=O)(=O)c1cc(-c2ccccc2)cc(S(=O)(=O)c2cc(Cl)c(CN)s2)c1
InChIKey: BWXFWGJYXOWCOQ-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 1 hr followed by substrate addition by ROS-Glo assay
Measurement: IC50 = 2164 nM (pChEMBL 5.670000076293945)
Descriptors: MW 441.98, ALogP 3.76, HBA 6, HBD 1, PSA 94.3, QED 0.65
Compound (SMILES): C[C@H](NC(=O)C1CCN(c2nc(N3CCOCC3)nc(-n3c(C(F)F)nc4ccccc43)n2)CC1)C(N)=O
InChIKey: SSIABNCMWUTBHR-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) expressed in baculovirus expression system by kinase-glo luminescence assay
Measurement: IC50 = 207 nM (pChEMBL 6.679999828338623)
Descriptors: MW 529.55, ALogP 1.19, HBA 10, HBD 2, PSA 144.39, QED 0.46
Compound (SMILES): Cc1ncc(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC2CCCCC2)C(=O)N[C@H](/C=C/S(C)(=O)=O)Cc2ccc(CN)cc2)s1
InChIKey: WEXVLMOBRFXARC-KQKGQGCBSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity (unknown origin) by cell based ABPP assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 659.92, ALogP 4.19, HBA 8, HBD 4, PSA 160.35, QED 0.21
Compound (SMILES): COC1O[C@]2(CC[C@H](N(C)CC3CCCCC3)CC2)c2ccccc21
InChIKey: UPNXBNHFBWGINS-NULPYHFVSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor in rat liver membranes incubated for 120 mins in the presence of sigma1 receptor ligand (+)-pentazocine by scintillation counting method
Measurement: Ki = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 343.51, ALogP 5.01, HBA 3, HBD 0, PSA 21.7, QED 0.77
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2O[C@@H](c3ccccc3)O[C@H]21
InChIKey: BCGDNNLMSKVHGV-ZQNBMKNCSA-N
Target: P2X purinoceptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51575
Assay: Antagonist activity at human P2X1R transfected in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 595.29, ALogP 1.13, HBA 14, HBD 5, PSA 257.13, QED 0.22
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](N)CC(C)C)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)O)C(C)C
InChIKey: NXHCAFUXBNDVPQ-HLQSCVHFSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00206
Assay: Antagonist activity at TLR4 (unknown origin) assessed as inhibition of proinflammatory cytokines
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 1434.75
Compound (SMILES): Cc1cc(CNc2cccc(C(=O)O)c2)ccc1OCc1ccc(F)cc1
InChIKey: DDCNGNDFKHLAQY-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Binding affinity to PPARalpha in human MIO-M1 cells assessed as increase in thermal stability preincubated for 3 hrs followed by exposure to 45.5 degree C for 10 mins by CETSA
Measurement: EC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 365.4, ALogP 5.02, HBA 3, HBD 2, PSA 58.56, QED 0.62
Compound (SMILES): Cl.O=C(Nc1ccccc1)c1cc(OC[C@@H]2CCCN2)no1
InChIKey: ZXGCJVGGSQRQCW-YDALLXLXSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from rat brain sigma2 receptor by PDSP assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 287.32, ALogP 2.06, HBA 5, HBD 2, PSA 76.39, QED 0.88
Compound (SMILES): C[C@H](NC(=O)c1c(-c2ccccc2)nnn1Cc1ccc(C(F)(F)F)cc1)c1ccc(C(=O)O)cc1
InChIKey: LBPJOXVWKUHDNV-INIZCTEOSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Mus musculus
UniProt: P32240
Assay: Antagonist activity at mouse EP4 expressed in CHO cells coexpressing G16-alpha assessed as intracellular calcium flux preincubated for 15 mins followed by addition of PGE2 by calcium flux assay
Measurement: IC50 = 906.3 nM (pChEMBL 6.039999961853027)
Descriptors: MW 494.47, ALogP 5.2, HBA 5, HBD 2, PSA 97.11, QED 0.37
Compound (SMILES): Cl.NCCCOc1cc(COc2ccccc2)on1
InChIKey: XXUVDWPYWPSOHQ-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from rat brain sigma2 receptor by PDSP assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 248.28, ALogP 1.98, HBA 5, HBD 1, PSA 70.51, QED 0.76
Compound (SMILES): CC1(C)Cc2cc(NC(=O)c3cnn4c(O)ccnc34)c(N3CCOCC3)cc2O1
InChIKey: OJCRUMWRMOCSGX-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human THP1-Xblue-MD2-CD14 cells assessed as reduction in LPS-induced NFkappaB transcription by measuring alkaline phosphatase level preincubated for 1 hr followed by LPS stimulation and measured after 20 hrs by quanti-blue reagent based reporter assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 409.45, ALogP 2.24, HBA 8, HBD 2, PSA 101.22, QED 0.68
Compound (SMILES): COc1ccc(C2=NN(C(C)C)C(=O)[C@@H]3CC=CC[C@H]23)cc1C#CC(N)=O
InChIKey: KIILUOSGHLGYRG-DLBZAZTESA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B catalytic domain using cAMP as substrate incubated for 20 mins by PDELight HTS cAMP phosphodiesterase Kit based luminometry
Measurement: Ki = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 365.43, ALogP 2.07, HBA 4, HBD 1, PSA 84.99, QED 0.66
Compound (SMILES): COc1ccc(C(=O)Nc2ccc(C(=O)N/N=C3\C(=O)Nc4ccc(Br)cc43)cc2)cc1
InChIKey: BVMQCPNVMDVRQM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of PDGFR-beta (unknown origin) by ELISA
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 493.32, ALogP 3.8, HBA 5, HBD 3, PSA 108.89, QED 0.47
Compound (SMILES): O=C(NCC1CCC(F)(F)CC1)c1c(Cl)ccc2nc(N3CCC(NCCO)C3)ccc12
InChIKey: NOBBKTYSVABXBL-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at P2X7R in LPS-stimulated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta release preincubated for 30 mins followed by BzATP stimulation and measured after 30 mins by sandwich ELISA
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 466.96, ALogP 3.6, HBA 5, HBD 3, PSA 77.49, QED 0.58
Compound (SMILES): Nc1nc2[nH]c(C3CC3)c(Cc3cccc(C(F)(F)F)c3)c(=O)n2n1
InChIKey: VJOUWHSXSNYAFP-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method
Measurement: Ki = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 349.32, ALogP 2.49, HBA 5, HBD 2, PSA 89.07, QED 0.76
Compound (SMILES): CCOC(=O)CN1C(=O)S/C(=C\c2ccc(-c3cc(C(=O)O)cc4ccccc34)o2)C1=O
InChIKey: SFDKMZFETFADOL-ODLFYWEKSA-N
Target: Excitatory amino acid transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P43003
Assay: Inhibition of human EAAT1 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 5 mins by liquid scintillation counting method
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 451.46, ALogP 4.4, HBA 7, HBD 1, PSA 114.12, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cc(Oc2nc(Nc3ccc(N4CCN(C)CC4)nc3OC)ccc2N2CCCCC2)ccc1C
InChIKey: PTEDRHAOUDENOU-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of cathepsin C in human U937 cells using H-Gly-Phe-AFC as substrate preincubated for 4 hrs followed by substrate addition and measured after 60 mins
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 557.7, ALogP 5.2, HBA 9, HBD 2, PSA 95.09, QED 0.34
Compound (SMILES): Oc1ccc2c(c1)CCCC(c1ccc(SC(F)(F)F)cc1)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: KSHPIANNCSKMIT-SANMLTNESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Estrogen Receptor Coactivator Assay: It is a competition assay, where binding of a test compound to a complex comprised of (i) His6-ERα298-554 protein representing ERα ligand-binding domain, (ii) Tb-labeled His6 antibody, (iii) a fluorescein-labeled PGC1α coactivator peptide (EAEEPSLLKKLLLAPANTQ), and (iv) estradiol, results in a decrease of the TR-FRET signal due to dissociation of the coactivator peptide. His6-ERα298-554 proteins were expressed as WT or D538G or Y537S mutants in E. coli and purified by affinity chromatography. The assay works in a homogeneous mix-and-read format. In a typical experiment, a 4 μL mixture of 0.5 nM His6-ERα298-554, 0.5 nM Tb-labeled His6 antibody, 250 nM PGC1a peptide, and 3 nM estradiol in 100 mM potassium phosphate, pH 7.4, 0.01% Tween-20, 0.02% NaN3, 5 mM DTT, was added to 40 nL test compound in DMSO and incubated overnight at room temperature. The TR-FRET 520:495 nm emission ratio was calculated and used to determine the IC50 value from a dose response curve fit to the 4-parameter logistic equation. The antagonist activity with respect to estrogen receptors in this test is given by the concentration which inhibits 50% of the estrogen receptor activity (or IC50) in nM.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 557.65, ALogP 8.11, HBA 4, HBD 1, PSA 32.7, QED 0.22
Compound (SMILES): C=CCCn1cc(-c2cccc(C(=O)N3CCOCC3)c2)c2cc[nH]c2c1=O
InChIKey: SMABWKWHQKFGDR-UHFFFAOYSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Inhibition of recombinant His-tagged TAF1 bromodomain 2 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 377.44, ALogP 3.05, HBA 4, HBD 1, PSA 67.33, QED 0.7
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCOCCOCC[n+]1c(C)cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc1C)C(=O)N[C@@H](CC(C)C)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: ZPPTZTSNISDQCQ-GUUUUNJBSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [3H] UR-MK300 from human neurotensin receptor 1 stably expressed in CHO cells incubated in dark after 30 mins by liquid scintillation counter analysis
Measurement: Ki = 1.288 nM (pChEMBL 8.890000343322754)
Descriptors: MW 1253.58
Compound (SMILES): COc1cc(/C=C2\SC(=S)N(C)C2=O)c(Br)cc1O
InChIKey: RQCGOFQLVIBWBZ-WMZJFQQLSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with interferon stimulatory DNA and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 360.25, ALogP 2.99, HBA 5, HBD 1, PSA 49.77, QED 0.65
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O)C(C)(C)C)C(C)C
InChIKey: QKAVRIPNEWKRQV-OAKFLICRSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 20.1 nM (pChEMBL 7.699999809265137)
Descriptors: MW 2444.87
Compound (SMILES): O=C(CCN1C(=O)c2ccccc2S1(=O)=O)Nc1ccc(O)c2ncccc12
InChIKey: DDMLDBPWJGUJHJ-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 using thiopeptide as substrate preincubated for 30 mins followed by substrate addition and measured every min for 20 mins by colorimetric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 397.41, ALogP 2.11, HBA 6, HBD 2, PSA 116.67, QED 0.65
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCNC(=N)Nc3ccc4[nH]c5c(c4c3)C[C@@]3(O)[C@H]4Cc6ccc(O)c7c6[C@@]3(CCN4CC3CC3)[C@H]5O7)c3ccc(S(=O)(=O)[O-])cc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21
InChIKey: KMHDVSRYNVXPOH-KMTFMGQQSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from recombinant human DOR transiently expressed in HEK293 cell membranes measured after 60 mins
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 1153.44
Compound (SMILES): C[C@H]1CCC[C@H]1Nc1nc(-c2ccncc2)nc2cnccc12
InChIKey: WIFZIPRZHKCGGL-SWLSCSKDSA-N
Target: Serine/threonine-protein kinase LATS1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95835
Assay: LATS1 Biochemical Assay: Homogenous Time Resolved Fluorescence (HTRF) Assay: The LATS1 biochemical HTRF assay was performed using the HTRF KinEASE-STK S1 kit (CisBio, catalogue number 62ST1PEC) according to manufacturer's instructions. Human LATS1 kinase domain protein was purchased from Carnabio (catalogue number 01-123), which harbors the catalytic domain of amino acids 589-1130, and was co-purified with human His-tagged MOBKL1A (NP_775-739). Compounds were added by ECHO liquid handler (Labcyte) into 384-well plates. Then 5 microlitre of the following solution was added into the wells (50 mM HEPES, 0.01% BSA, 100 nM Orthaovanadate, 1 mM MgCl2, 1 mM DTT, 0.6 ng/microlitre LATS1 enzyme (Carnabio, 01-123), 2 micromolar STK1 localising aid (CisBio)), followed with 5 microlitre of 2 mM ATP in the kinase buffer (50 mM HEPES, 0.01% BSA, 100 nM Orthaovanadate, 1 mM MgCl2, 1 mM DTT) and incubated for 30 minutes at room temperature. 10 microlitre of detection mix (50 mM HEPES, 0.01% BSA, 100 nM Orthaovanadate, 1 mM MgCl2, 1 mM DTT, STK Antibody-Cryptate (CisBio), Streptavidin-XL665 (CisBio), 500 micromolar potassium fluoride, 50 nM EDTA) was added to each well and incubated for 1 hour at room temperature. Plates were read on Pherastar (BMG Labtech) for HTRF (665 nm/620 nm). The IC50 is measured when the effect of the compound reduces the HTRF signal by 50%.
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 305.38, ALogP 3.69, HBA 5, HBD 1, PSA 63.59, QED 0.8