lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(Cn2c(N3CCNCC3)nc3c(N4CCC[C@H]4CN)cc(Cl)cc32)cc(C)c1F
InChIKey: CAPZSPOPEHSYOZ-FQEVSTJZSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Activation of SOS1 in human HeLa cells expressing wild type KRAS assessed as induction of ERK1/2 T202/Y204 phosphorylation incubated for 30 mins by In-cell Western assay
Measurement: EC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 471.02, ALogP 3.83, HBA 6, HBD 2, PSA 62.35, QED 0.59
Compound (SMILES): Cc1ccn(-c2ccc(C(=O)N3CCCC(=O)c4ccccc43)c(Cl)c2)n1
InChIKey: CSUVIYPWZHXAHY-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Displacement of [3H]-AVP from human V2 receptor expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 379.85, ALogP 4.46, HBA 4, HBD 0, PSA 55.2, QED 0.66
Compound (SMILES): COC(=O)[C@@]12CN(Cc3ccccc3)C[C@@H]1C[C@H]1[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]12C
InChIKey: MWXMXEGVUOYLAE-FCQBLWMMSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Induction of nuclear translocation of human recombinant ProLabel-tagged glucocorticoid receptor expressed in CHO-K1 cells after 3 hrs by luminescence method
Measurement: EC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 511.61, ALogP 4.21, HBA 5, HBD 1, PSA 66.84, QED 0.62
Compound (SMILES): COCc1ccc(-c2cc3c(N[C@@H](C)c4nn(C)cc4C)c(C(N)=O)cnc3cc2F)cn1
InChIKey: KQYCKJMIYOJHEH-AWEZNQCLSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells assessed as reduction in Chk1 phosphorylation at Ser-345 residue after 60 mins in presence of 4-nitroquinoline-1-oxide by Hoechst 33258 staining based plate reader analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 448.5, ALogP 3.9, HBA 7, HBD 2, PSA 107.95, QED 0.44
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4cccc(OC)c4F)cc3)c3cncc(OC)c32)C1
InChIKey: LLRUOFRCNQYKAO-LJQANCHMSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Assay: Measurements were performed in a reaction volume of 15 μL using 384-well assay plates. Kinase enzyme, inhibitor, ATP and 1 μM peptide substrate were incubated in a reaction buffer compose of Hepes 50 mM (pH7.0), NaN3 0.02%, BSA 0.01%, Orthocanadate 0.1 mM. After one hour, the kinase reaction was quenched by the addition of Eμ-labeled antibody and XL-665 in 1ÃDetection buffer containing 60 mM EDTA (Cisbio), and the mixture was allowed to incubate for one hour. The HTRF signal was measured on a multimode plate reader (EnVisionÂ® Multilabel Reader, Perkin Elmer) with an excitation wavelength (λEx) of 330 nm and detection wavelengths (λEm) of 615 and 665 nm. Activity was determined by the ratio of the fluorescence at 665 nm to that at 615 nm. For each compound, enzyme activity as measured at various concentrations of compound, Negative control reactions were performed in the absence of inhibitor in two replicates and eight no enzyme controls.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 502.55, ALogP 5.4, HBA 7, HBD 0, PSA 78.71, QED 0.32
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3cnc(C(F)F)cn3)ccc2F)C=C(CF)OC(N)=N1
InChIKey: YOCCHFJQUBFRGO-SFHVURJKSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SH-SY5Y cells transfected with human wild type beta-APP assessed as reduction in amyloid beta (1 to 40) levels after 24 hrs by HTRF assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 409.34, ALogP 3.22, HBA 6, HBD 2, PSA 102.49, QED 0.74
Compound (SMILES): CCCCCCOc1cc(Cl)c2c(CCC(=O)O)c(C(=O)O)[nH]c2c1
InChIKey: ZFPCHYJCZVFAIV-UHFFFAOYSA-N
Target: Uracil nucleotide/cysteinyl leukotriene receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q09QM4
Assay: Agonist activity at rat GPR17 expressed in HEK293 cells assessed as induction of intracellular calcium mobilization by calcium 5-dye based assay
Measurement: EC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 367.83, ALogP 4.5, HBA 3, HBD 3, PSA 99.62, QED 0.54
Compound (SMILES): C#CCN(C)CCCCOc1ccc2ccc(=O)oc2c1
InChIKey: QYIDTLNEEJCIJR-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using p-tyramine as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by amplex red reagent based fluorescence assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 285.34, ALogP 2.52, HBA 4, HBD 0, PSA 42.68, QED 0.45
Compound (SMILES): CCN(CC)[C@@H](C)CNC(=O)c1cc(-c2cnn3ccc(-c4cccs4)nc23)nc(N2CC(OC)C2)c1
InChIKey: UCHOYOABTVPSLZ-SFHVURJKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 4160 nM (pChEMBL 5.380000114440918)
Descriptors: MW 519.68, ALogP 3.81, HBA 9, HBD 1, PSA 87.89, QED 0.34
Compound (SMILES): CCc1cccc(-c2c(F)cccc2C(O)(CCCNC(=O)OC)[C@@H]2CCCN(C(=O)CCCCCN)C2)c1
InChIKey: RJCONYSMTQWQBS-KZQYXEPFSA-N
Target: Renin (SINGLE PROTEIN), Homo sapiens
UniProt: P00797
Assay: Inhibition of renin in human plasma using angiotensinogen as substrate measured for 90 mins by [125I]-angiotensin based radioimmunoassay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 541.71, ALogP 5.14, HBA 5, HBD 3, PSA 104.89, QED 0.3
Compound (SMILES): CCCCn1cnc2c(Nc3cc(OC)cc(OC)c3)nc(N[C@H]3CC[C@H](N)CC3)nc21
InChIKey: RLXAIBAERUVCCV-WKILWMFISA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of recombinant human N-terminal GST-His6 tagged PDGFRalpha (Q551 to L1089 residues) expressed in Sf9 insect cells using poly(Ala,Glu,Lys,Tyr)6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 1496 nM (pChEMBL 5.829999923706055)
Descriptors: MW 439.56, ALogP 4.07, HBA 9, HBD 3, PSA 112.14, QED 0.46
Compound (SMILES): CC1=C(CC(=O)NCCOc2ccc(S(N)(=O)=O)cc2)c2cc(F)ccc2/C1=C/c1ccc([S+](C)[O-])cc1
InChIKey: SKOXNUJTXFITBK-MFKUBSTISA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase-2 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 554.67, ALogP 4.12, HBA 5, HBD 2, PSA 121.55, QED 0.3
Compound (SMILES): CN(Cc1ccccc1)Cc1ccc(NC(=O)/C=C/c2ccccc2)cc1
InChIKey: KMEVTHHMQHAIQF-SAPNQHFASA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured up to 180 secs by spectrophotometric analysis
Measurement: IC50 = 8210 nM (pChEMBL 5.090000152587891)
Descriptors: MW 356.47, ALogP 4.97, HBA 2, HBD 1, PSA 32.34, QED 0.61
Compound (SMILES): Fc1ccc2[nH]c(CNc3nc(N4CCOCC4)nc4c3ncn4-c3ccc(Cl)nc3)nc2c1F
InChIKey: JYIDOOYLGITHSS-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 1195 nM (pChEMBL 5.920000076293945)
Descriptors: MW 497.9, ALogP 3.47, HBA 9, HBD 2, PSA 109.67, QED 0.36
Compound (SMILES): COc1cc2c(NC3CCN(C)CC3)cc(-c3ccc(C)o3)nc2cc1OC1CC2(C1)CN(C)C2
InChIKey: IQRVFHPCSDGBCR-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human DNMT1 using polydeoxyinosine polydeoxycytosine DNA as substrate after 15 mins in presence of SAM by TR-FRET assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 476.62, ALogP 4.79, HBA 7, HBD 1, PSA 63, QED 0.55
Compound (SMILES): CC(C)(O)CNC(=O)C[C@@H]1CCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: WKDNXLPZDBZVOG-KRWDZBQOSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR in human HepG2 cells by receptor transactivation assay
Measurement: EC50 = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 586.53, ALogP 3.93, HBA 5, HBD 3, PSA 106.94, QED 0.43
Compound (SMILES): COc1ccc(NC(=O)N2CCN(c3nc(N)nc4scnc34)[C@@H](C)C2)c(C)c1
InChIKey: ONBMVXFPPPIHMK-LBPRGKRZSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Inhibition of PI4K3beta in human PBMC assessed as reduction in mitomycin-C treated human RPMI1788 cells-stimulated lymphocyte proliferation by measuring reduction in [3H]thymidine incorporation preincubated for 5 days followed by [3H]thymidine addition measured after 18 hrs by liquid scintillation counting method
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 413.51, ALogP 2.73, HBA 8, HBD 2, PSA 109.5, QED 0.68
Compound (SMILES): Cc1ccn2c(NC3CCCCC3)c(-c3ccc(OCCCN4C(=O)c5ccccc5C4=O)cc3)nc2c1
InChIKey: CPKUUCBGSVSQHH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 (1 to 460 residues) expressed in baculovirus expression system using Rh-EVNLDAEFK-quencher as substrate after 90 mins by FRET assay
Measurement: Ki = 4.38 nM (pChEMBL 8.359999656677246)
Descriptors: MW 508.62, ALogP 6.12, HBA 6, HBD 1, PSA 75.94, QED 0.23
Compound (SMILES): Cc1cc(-c2c(Cl)cncc2OC(F)F)cc2c1NC(=O)C2
InChIKey: HNSMBMPEJNXIBA-UHFFFAOYSA-N
Target: GRIA1/CACNG2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y698
Assay: Modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 324.71, ALogP 3.81, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): O=C([C@@H]1CSCN1Cc1cc(Cl)ccc1C(F)(F)F)N1CCN(C2CC2)c2ccccc21
InChIKey: MRERQHIEQKJKBV-NRFANRHFSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at human TGR5 expressed in HEK293 cells assessed as increase in intracellular cAMP level by HTRF assay
Measurement: EC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 481.97, ALogP 5.25, HBA 4, HBD 0, PSA 26.79, QED 0.6
Compound (SMILES): Cc1cc(C)c2cc(C(=O)NC3CN(c4ncc(C(F)(F)F)cn4)C3)ccc2n1
InChIKey: PLKPPGQZOQNCNE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation of rat M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 3890.45 nM (pChEMBL 5.409999847412109)
Descriptors: MW 401.39, ALogP 3.28, HBA 5, HBD 1, PSA 71.01, QED 0.73
Compound (SMILES): Cc1nc(C)c(COc2ccc(/C=C/C(=O)NCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc2)nc1C
InChIKey: SPPVNYAEVQJRRF-DYTRJAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by DTNB addition for 5 mins and subsequent addition of substrate measured after 3 mins by Ellman's method
Measurement: IC50 = 303.7 nM (pChEMBL 6.519999980926514)
Descriptors: MW 577.77, ALogP 7.21, HBA 6, HBD 2, PSA 89.03, QED 0.13
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@H](N(C)C(=O)/C=C/c4ccoc4)CC[C@H]4[C@@H](C2)N(S(=O)(=O)c2ccccc2)CC[C@@]341
InChIKey: CSTWAODTAKMZMG-XADNFDQUSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human OX2R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular Ca2+ release preincubated for 15 mins followed by orexin A addition by Fura 2-AM dye based fluorescence assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 560.67, ALogP 4.26, HBA 6, HBD 0, PSA 89.29, QED 0.42
Compound (SMILES): CCC/C=C1/C(=O)O[C@@H](C)[C@H]1O
InChIKey: WQLMRKLWOQAVAU-MGRRSFKLSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Displacement of [3H]rosiglitazone from human PPAR-gamma incubated for 1 day by radioligand binding assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 170.21, ALogP 1.02, HBA 3, HBD 1, PSA 46.53, QED 0.5
Compound (SMILES): CCCCC/C=C\[C@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NC1CC1
InChIKey: QWOSQZCKUTULAW-VVFVXTANSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]CP-55,940 from CB1 receptor in rat brain membranes in presence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 357.58, ALogP 6.66, HBA 1, HBD 1, PSA 29.1, QED 0.26
Compound (SMILES): COc1cnccc1-c1nc2cc(NC(=O)[C@H](C)Oc3cccc(Cl)c3Cl)ccc2o1
InChIKey: GXJXYKPJTNSOEN-LBPRGKRZSA-N
Target: GMP reductase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2T1
Assay: Inhibition of human GMPR2 using GMP as substrate by spectrophotometric method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 458.3, ALogP 5.61, HBA 6, HBD 1, PSA 86.48, QED 0.4
Compound (SMILES): CC(C)(C)NC(=O)CN1Cc2ccc(-c3nc(NC4CCOCC4)ncc3Cl)cc2C1=O
InChIKey: ZREYQWDDINYDOY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of full length human N-terminal MAHHHHHH-tagged ERK2 expressed in Escherichia coli BL21 (DE3) using ATF2-GFP as substrate after 30 mins by time-resolved fluorescence assay
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 457.96, ALogP 3.26, HBA 6, HBD 2, PSA 96.45, QED 0.71
Compound (SMILES): Cc1ccc(-c2cc(NC3CCN(C)CC3)c3cc(Cl)c(OCCCN4CCCC4)cc3n2)o1
InChIKey: FKRRYTPCUFOKGU-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human DNMT1 using polydeoxyinosine polydeoxycytosine DNA as substrate after 15 mins in presence of SAM by TR-FRET assay
Measurement: IC50 = 298 nM (pChEMBL 6.53000020980835)
Descriptors: MW 483.06, ALogP 5.83, HBA 6, HBD 1, PSA 53.77, QED 0.41
Compound (SMILES): CN1CCN(c2cc(CN(C)[C@@H]3CCCc4cccnc43)ncn2)CC1
InChIKey: LPTRCGOYHAYNCF-GOSISDBHSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at CXCR4 in human CD4+ T cells assessed as inhibition of CXCL12-mediated cytosolic calcium level preincubated with compounds followed by CXCL12 stimulation by calcium 4 dye-based FLIPR assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 352.49, ALogP 2.13, HBA 6, HBD 0, PSA 48.39, QED 0.84
Compound (SMILES): CC1(C)CCCN(CC(O)Cn2c3ccc(F)cc3c3cc(F)ccc32)C1=O
InChIKey: QGHIRYFCAFOZSO-UHFFFAOYSA-N
Target: Period circadian protein homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O15055
Assay: Per2 Assay: Compounds were screened by using a high-throughput circadian assay system as previously described in Zhang, E. E. et al. Cell, 2009, 139, 199-210. In brief, stable U20S reporter cells harboring Per2-dLuc were plated at a density of 30,000 cells/well in Corning 96-well, solid white, flat bottom, TC-treated microplates (Corning), and incubated for 48 hours at 37° C. in the presence of 5% CO2 in a medium of Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin (100 units/mL)-streptomycin (100 μg/mL). Compounds of formula I are solubilized in dimethylsulfoxide (DMSO), typically at a concentration of 2 mg/mL. DMSO stocks are then serially diluted in DMSO, typically diluting 3-fold for each dilution step. Following the 48 h period, cell culture medium is removed from plated cells and cells are synchronized with 200 μL/well of complete cell culture medium (described above), supplemented with 5 μM forskolin (Tocris) and 1 mM beetle luciferin (Promega). Immediately following synchronization, 1 μL of compound dilution is added to each well. Plates are sealed, shaken briefly, and gene expression was monitored by measuring luminescence (Tecan Infinite M200 or Tecan Infinite M200 Pro) continuously for a minimum of 3 days at 35° C. Raw luminescence data (counts) are first analyzed using Multicycle software (Actimetrics, Inc.) to determine the amplitude (amp), period, and phase (phz) for each compound concentration. The period length for control wells (i.e. no compound, DMSO only) should be 26-30 h. Amp data are then plotted against the logarithm compound concentration (M) and analyzed by nonlinear regression analysis to determine the EC50.
Measurement: EC50 = 463 nM (pChEMBL 6.329999923706055)
Descriptors: MW 386.44, ALogP 4.08, HBA 3, HBD 1, PSA 45.47, QED 0.73
Compound (SMILES): CCn1cc(-n2ncc3cc(O[C@H](c4ccccc4)[C@H](C)NC(=O)C(C)(F)F)ccc32)ccc1=O
InChIKey: GFAQUXPHHREEAJ-XDHUDOTRSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transactivation activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: EC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 480.52, ALogP 4.49, HBA 6, HBD 1, PSA 78.15, QED 0.4
Compound (SMILES): COc1cc2c(cc1-c1cnn3ccc(-c4ccnc5[nH]ccc45)cc13)CN(C(C)=O)C2
InChIKey: VPBQVFOYPXGRAU-UHFFFAOYSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Homo sapiens
UniProt: P17252
Assay: Inhibition of full-length N-terminal GST-fused human PKC-alpha expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 423.48, ALogP 4.42, HBA 5, HBD 1, PSA 75.52, QED 0.47
Compound (SMILES): Cc1cccc(NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@]2(C)CCC[C@]3(C)c4cc(S(=O)(=O)N[C@@H](Cc5ccccc5)C(=O)Nc5cccc(C)c5)c(C(C)C)cc4CC[C@@H]23)c1
InChIKey: MQAGCLXEIBRDCG-ULBMYSQZSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 (Phe21 to Gly467 residues) expressed in mouse myeloma cells using Mca-Pro-LeuGly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 853.14, ALogP 9.33, HBA 5, HBD 4, PSA 133.47, QED 0.09
Compound (SMILES): COc1ccc(-c2c3c4cc(OC)c(OCCCNC(=N)N)cc4oc(=O)c3n3ccc4cc(O)c(OC)cc4c23)cc1O.O=C(O)C(F)(F)F
InChIKey: BAWKDBFGNNKJBC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant wild type EGFR (696 to C-terminal residues) (unknown origin) preincubated for 30 mins followed by poly (Glu-Tyr) biotinylated peptide substrate addition measured after 30 mins in presence of ATP by ELISA
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 598.61, ALogP 4.71, HBA 10, HBD 5, PSA 173.9, QED 0.07
Compound (SMILES): C[C@@H]1CCC[C@H](C[C@@H]2Cc3cc(O)cc(O)c3C(=O)O2)O1
InChIKey: WOMKDMUZNBFXKG-WQAKAFBOSA-N
Target: Lysine--tRNA ligase (SINGLE PROTEIN), Homo sapiens
UniProt: Q15046
Assay: Inhibition of human KRS expressed in Escherichia coli BL21 using tRNA(Lys) as substrate after 1 hr in presence of L-lysine by AMP-GLO assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 292.33, ALogP 2.53, HBA 5, HBD 2, PSA 75.99, QED 0.82
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-c3c(C4CC4)n[nH]c3C)c12
InChIKey: VMFXJMOASBHFCY-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: IC50 = 11.7 nM (pChEMBL 7.929999828338623)
Descriptors: MW 414.47, ALogP 4.97, HBA 6, HBD 2, PSA 105.51, QED 0.43
Compound (SMILES): Cc1cc(COc2ccc(S(=O)(=O)N(C)C3(C(=O)NO)CN(C(=O)C(C)C)C3)cc2)c2ccccc2n1
InChIKey: BQDVTMRZPWSYOT-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of TACE in NHEK assessed as reduction in LPS/TPA-stimulated TNFalpha production preincubated for 1 hr followed by LPS/TPA stimulation for 24 hrs by HTRF assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 526.62, ALogP 2.49, HBA 7, HBD 2, PSA 129.14, QED 0.34
Compound (SMILES): O=C1N(CC(O)Cn2c3ccc(F)cc3c3cc(F)ccc32)CCC1(F)F
InChIKey: JPMXZOVVSGBPDK-UHFFFAOYSA-N
Target: Period circadian protein homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O15055
Assay: Per2 Assay: Compounds were screened by using a high-throughput circadian assay system as previously described in Zhang, E. E. et al. Cell, 2009, 139, 199-210. In brief, stable U20S reporter cells harboring Per2-dLuc were plated at a density of 30,000 cells/well in Corning 96-well, solid white, flat bottom, TC-treated microplates (Corning), and incubated for 48 hours at 37° C. in the presence of 5% CO2 in a medium of Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin (100 units/mL)-streptomycin (100 μg/mL). Compounds of formula I are solubilized in dimethylsulfoxide (DMSO), typically at a concentration of 2 mg/mL. DMSO stocks are then serially diluted in DMSO, typically diluting 3-fold for each dilution step. Following the 48 h period, cell culture medium is removed from plated cells and cells are synchronized with 200 μL/well of complete cell culture medium (described above), supplemented with 5 μM forskolin (Tocris) and 1 mM beetle luciferin (Promega). Immediately following synchronization, 1 μL of compound dilution is added to each well. Plates are sealed, shaken briefly, and gene expression was monitored by measuring luminescence (Tecan Infinite M200 or Tecan Infinite M200 Pro) continuously for a minimum of 3 days at 35° C. Raw luminescence data (counts) are first analyzed using Multicycle software (Actimetrics, Inc.) to determine the amplitude (amp), period, and phase (phz) for each compound concentration. The period length for control wells (i.e. no compound, DMSO only) should be 26-30 h. Amp data are then plotted against the logarithm compound concentration (M) and analyzed by nonlinear regression analysis to determine the EC50.
Measurement: EC50 = 716 nM (pChEMBL 6.139999866485596)
Descriptors: MW 380.34, ALogP 3.3, HBA 3, HBD 1, PSA 45.47, QED 0.71
Compound (SMILES): COc1cccc(F)c1-c1ccnc(Nc2ccc(S(=O)(=O)Nc3nccs3)cc2)n1
InChIKey: BQRWVMGYVBRTGW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human PLK1 kinase domain using 5-TAMRA-RGSFNDTLDFD-NH2 substrate and ATP incubated for 90 mins by fluorescent polarization assay
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 457.51, ALogP 4.29, HBA 8, HBD 2, PSA 106.1, QED 0.43
Compound (SMILES): CN1CC[C@@](O)(C#Cc2cccc(-c3cc4ccccc4c(C(N)=O)n3)c2)C1=O
InChIKey: BHMWTKSKABRIAP-QHCPKHFHSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) expressed in HEK293 cells harboring NFkB-Luc assessed as reduction in NFkB signal after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 385.42, ALogP 1.95, HBA 4, HBD 2, PSA 96.52, QED 0.66
Compound (SMILES): CN1CCN(c2nc(NCc3nc4c(F)c(F)ccc4[nH]3)c3ncn(-c4ccnc(F)c4)c3n2)CC1
InChIKey: XZOWEDFOFIQNGN-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 494.49, ALogP 2.87, HBA 9, HBD 2, PSA 103.68, QED 0.36
Compound (SMILES): C/C(=C\CCCOc1ccccc1CN(C)C(=O)c1ccc(-c2ccco2)cc1)C(=O)O
InChIKey: UOUIWYBSJFMAKV-UFWORHAWSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Activation of human PPARdelta LBD expressed in CHO-K1 cells by beta galactosidase enzyme fragment complement based fluorescence assay
Measurement: EC50 = 1850 nM (pChEMBL 5.730000019073486)
Descriptors: MW 433.5, ALogP 5.41, HBA 4, HBD 1, PSA 79.98, QED 0.34
Compound (SMILES): O=C1Nc2ccc(Cl)cc2C1=NN1CCOCC1
InChIKey: YNRWWXIQNOMIBW-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant catalytic human GST-tagged LLRK2 G2019S mutant (970 to 2527 residues) expressed in baculovirus expression system using LRRKtide as substrate after 1 hr by alexaFluor-ADP-based FRET assay
Measurement: IC50 = 1460 nM (pChEMBL 5.840000152587891)
Descriptors: MW 265.7, ALogP 1.33, HBA 4, HBD 1, PSA 53.93, QED 0.83
Compound (SMILES): CC1(C)NC(=O)c2sc(-c3ccncc3)cc2N1
InChIKey: LHJWDAABBSKSEQ-UHFFFAOYSA-N
Target: CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBU7
Assay: Inhibition of recombinant human Cdc7 (1 to 574 residues)/human N-terminal GST-tagged DBF4 (1 to 674 residues) expressed in baculovirus expression system using His-tagged MCM2 as substrate preincubated for 10 mins followed by ATP addition by HTRF assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 259.33, ALogP 2.7, HBA 4, HBD 2, PSA 54.02, QED 0.83
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-n3nnc4ccccc43)c12
InChIKey: QNYYNLYQKNPSRP-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 411.43, ALogP 4.13, HBA 8, HBD 1, PSA 107.54, QED 0.47
Compound (SMILES): Cl.NCc1ccc(Oc2ccc(S(=O)(=O)C[C@H]3CS3)cc2)cc1
InChIKey: DRGIZFGSEKSFIC-XFULWGLBSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Non-competitive inhibition of human recombinant MMP8 catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate
Measurement: Ki = 8590 nM (pChEMBL 5.070000171661377)
Descriptors: MW 335.45, ALogP 2.83, HBA 5, HBD 1, PSA 69.39, QED 0.82
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N2
InChIKey: YDMCKCUHYZRPDS-FYHDBFLGSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Antagonist activity at rat alpha3beta4 nACHR expressed in Xenopus laevis oocytes assessed as inhibition of acetyl choline-induced membrane currents pre-incubated for 5 mins prior to acetyl choline pulse at -70 mV potential by two-electrode voltage clamp assay
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 1565.92
Compound (SMILES): CN1CC[C@@](O)(C#Cc2ccnc(-n3nc(C(N)=O)cc3C3CC3)c2)C1=O
InChIKey: WFIYKEJGYKFLJS-IBGZPJMESA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: NIK Enzyme Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5′-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5′-diphosphate) assay (BellBrook Labs). Purified NIK (0.5 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl2, 2 mM dithiothreitol, 10 μM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 7 μg/mLADP antibody and 5 nM ADP-MR121 633 tracer. Reactions were quenched by the addition of 20 mM 2,2′,2″,2′″-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation at 633 nm with a Fluorescence Correlation Spectroscopy Plus reader (Evotec AG). Equilibrium dissociation constant (Ki) values for NIK inhibitors are calculated from plots of activity vs. inhibitor concentration using Morrison's quadratic equation that accounts for the potential of tight binding, and by also applying the conversion factor that accounted for competitive inhibition and the concentration of substrate used in the assay relative to its Michaelis constant (Km).
Measurement: Ki = 15.8 nM (pChEMBL 7.800000190734863)
Descriptors: MW 365.39, ALogP 0.19, HBA 6, HBD 2, PSA 114.34, QED 0.75
Compound (SMILES): CC(C)(C)c1ccc(C(=O)/C(C#N)=N/Nc2cc(F)c(F)c(F)c2)cc1
InChIKey: GXXOREJDHQJZJZ-PCLIKHOPSA-N
Target: Rap guanine nucleotide exchange factor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O95398
Assay: Antagonist activity at recombinant full length EPAC1 (unknown origin) assessed as inhibition of cAMP-mediated Rap1b-BODIPY GDP nucleotide exchange activity
Measurement: IC50 = 24400 nM (pChEMBL 4.610000133514404)
Descriptors: MW 359.35, ALogP 4.58, HBA 4, HBD 1, PSA 65.25, QED 0.38
Compound (SMILES): CC(C(=O)NCCCOc1ccc(S(N)(=O)=O)cc1)c1ccc(-c2ccccc2)c(F)c1
InChIKey: YKEULJQRBHWKDW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase-2 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 456.54, ALogP 3.83, HBA 4, HBD 2, PSA 98.49, QED 0.48
Compound (SMILES): O=S(=O)(Oc1cccc(/C=C/c2cc(O)cc(O)c2)c1)C1CC2OC1C(c1ccc(O)cc1)=C2c1ccc(O)cc1
InChIKey: ALOCLAGPDQUYKZ-SNAWJCMRSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to human ERbeta LBD after 2 hrs in absence of light by competitive fluorometric binding assay
Measurement: Ki = 4577.8 nM (pChEMBL 5.340000152587891)
Descriptors: MW 570.62, ALogP 5.54, HBA 8, HBD 4, PSA 133.52, QED 0.17
Compound (SMILES): CC(C)N(NC(=O)c1ccc2ccccc2c1)C(=O)C1CNC[C@H]1C(=O)N[C@H]1CC(=O)OC1O
InChIKey: DWOSJQDDZRKCOZ-GBGMBEOMSA-N
Target: Caspase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29466
Assay: Inhibition of human recombinant caspase-1 using AC-WEHD-AMC as substrate at Km after 20 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 468.51, ALogP 0.31, HBA 7, HBD 4, PSA 137.07, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C2\NC(=O)/C(=C3/C(=O)Nc4ccc(Br)cc43)S2)cc1
InChIKey: SJBBKDUMZRKKBW-YPKPFQOOSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic carbonic anhydrase 2 by stopped-flow CO2 hydrase assay
Measurement: Ki = 210.5 nM (pChEMBL 6.679999828338623)
Descriptors: MW 479.34, ALogP 2.31, HBA 6, HBD 3, PSA 130.72, QED 0.57
Compound (SMILES): N[C@@H](Cc1ccc(Cl)c(-c2cccc(O)c2)c1)C(=O)O
InChIKey: DSEZNOSITRSTCW-AWEZNQCLSA-N
Target: Glutamate receptor 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19492
Assay: Displacement of [3H]AMPA from rat GluA3 receptor flip isoform expressed in sf9 insect cell membranes by TopCount method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 291.73, ALogP 2.67, HBA 3, HBD 3, PSA 83.55, QED 0.81
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cc(Cl)c(O)c([N+](=O)[O-])c2)c1
InChIKey: SPIZPABAPBQRSM-UHFFFAOYSA-N
Target: Dual specificity protein phosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P51452
Assay: Inhibition of human VHR using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 436.81, ALogP 5.64, HBA 6, HBD 2, PSA 126.7, QED 0.31
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)COCc2ccccc2)n1
InChIKey: YTBZQGYFOZNNDW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR E746_A750 deletion/T790M mutant in human growth-resistant PC9 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 589.1, ALogP 5.58, HBA 9, HBD 2, PSA 101.08, QED 0.23
Compound (SMILES): Nc1ccc(S(=O)(=O)N2C(=O)C(c3ccccc3)N(S(=O)(=O)c3ccc(N)cc3)C(=O)C2c2ccccc2)cc1
InChIKey: QUOALYCSYFNATG-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 20 mins at 1 min interval by Ellman's method
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 576.66, ALogP 3.08, HBA 8, HBD 2, PSA 160.94, QED 0.33
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)C(C)(C)C(=O)Nc4ccc(F)cc4)cc3)c2cc1OC
InChIKey: NZVVNSNFDDECIU-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of cMet (unknown origin) using poly(Glu, Tyr)4:1 substrate and ATP incubated fro 60 mins by ELISA
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 503.53, ALogP 5.79, HBA 6, HBD 2, PSA 98.78, QED 0.3
Compound (SMILES): COc1ccc(-c2nc3cc(NC(=O)c4cccc([N+](=O)[O-])c4)ccc3o2)cc1OC
InChIKey: NCQJSDIBVNYQPN-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of recombinant human N-terminal His-tagged COX2 expressed in baculovirus infected Sf21 cells assessed as reduction in prostaglandin production by enzyme immunoassay
Measurement: IC50 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 419.39, ALogP 4.67, HBA 7, HBD 1, PSA 116.73, QED 0.36
Compound (SMILES): Nc1c2c(nc3cc(-c4cncnc4)ccc13)CCC(C(=O)NCCCc1ccccc1)C2
InChIKey: QSAIYXTWZROLFQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine as substrate preincubated for 20 mins followed by substrate addition measured every 2 mins for 20 mins by Ellman's method
Measurement: IC50 = 18020 nM (pChEMBL 4.739999771118164)
Descriptors: MW 437.55, ALogP 4.13, HBA 5, HBD 2, PSA 93.79, QED 0.44
Compound (SMILES): CC(C)Nc1nc(N[C@H]2CC[C@@H](NC(=O)N[C@@H](CO)C(C)C)CC2)c2cc(-c3cccc(F)c3)cnc2n1
InChIKey: JVPUVRRKNUBWPR-ZDXQCDESSA-N
Target: Atrial natriuretic peptide receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P16066
Assay: Agonist activity at human NPR-A expressed in CHO cells assessed as increase in cGMP accumulation after 30 mins by radioimmunoassay
Measurement: EC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 523.66, ALogP 4.69, HBA 7, HBD 5, PSA 124.09, QED 0.28
Compound (SMILES): CC(C(=O)NCCCOc1ccc(S(N)(=O)=O)cc1)c1cccc(C(=O)c2ccccc2)c1
InChIKey: LCMKFYRXIFBJTQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase-2 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 466.56, ALogP 3.25, HBA 5, HBD 2, PSA 115.56, QED 0.35
Compound (SMILES): CC(=O)N(CCCC[C@@H]1NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccc(O)cc2)NC1=O)C(=O)c1ccccc1-c1c2ccc(=O)cc-2oc2cc(O)ccc12
InChIKey: CHJDZBMXBJMWPL-IURAFAQNSA-N
Target: EH domain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4M9
Assay: Binding affinity to GST-fused EHD1 EH domain (unknown origin) expressed in Escherichia coli BL21 cells measured after 1 hr in presence of 150 mM NaCl by fluorescence polarization assay
Measurement: Kd = 15100 nM (pChEMBL 4.820000171661377)
Descriptors: MW 1321.36
Compound (SMILES): CCCCC/C=C\[C@@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NCCO
InChIKey: HPZWGIGIINAFKI-QUMJFYJXSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]CP-55,940 from CB1 receptor in rat brain membranes in presence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 361.57, ALogP 5.49, HBA 2, HBD 2, PSA 49.33, QED 0.28
Compound (SMILES): Cn1ncc2c(NC3(c4ccc(C(F)(F)F)cc4)CC3)nc(C3CC3)nc21
InChIKey: NVBNLGCHMMFYDD-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibitory Activity Assay (Lab B): In a typical experiment the PDE2 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. Rhesus PDE2A3 was amplified from rhesus macaque brain cDNA (Biochain Institute, Hayward, Calif.) using primers based on human PDE2A sequence (accession NM_002599.3) where the forward primer containing a Kozak consensus was 5′-gccaccatggggcaggcatgtggc-3′ and the reverse primer was 5′-tcactcagcatcaaggctgca-3′. Amplification with Easy-A High-Fidelity PCR cloning enzyme (Stratagene, La Jolla, Calif.) was 95° C. for 2 minutes followed by thirty three cycles of 95° C. for 40 seconds, 52° C. for 30 seconds, and 72° C. for 2 minutes 48 seconds. Final extension was 72° C. for 7 minutes. The PCR product was TA cloned into pcDNA3.3-TOPO (Invitrogen, Carlsbad, Calif.) according to standard protocol. A consensus sequence was developed from multiple clones and then deposited into GenBank (EU812167). AD293 cells (Stratagene, La Jolla, Calif.) with 70-80% confluency were transiently transfected with rhesus PDE2A3/pcDNA3.3-TOPO using Lipofectamine 2000 according to manufacturer specifications (Invitrogen, Carlsbad, Calif.). Cells were harvested 48 hours post-transfection and lysed by sonication (setting 3, 10×5 sec pulses) in a buffer containing 20 mM HEPES pH 7.4, 1 mM EDTA and Complete Protease Inhibitor Cocktail Tablets (Roche, Indianapolis, Ind.). Lysate was collected by centrifugation at 75,000×g for 20 minutes at 4° C. and supernatant utilized for evaluation of PDE2 activity.
Measurement: Ki = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 373.38, ALogP 4.36, HBA 5, HBD 1, PSA 55.63, QED 0.74
Compound (SMILES): OC[C@@H]1N[C@H]([C@@H](O)CO)[C@@H]1O
InChIKey: DVZPQZNDYFWQHJ-UNTFVMJOSA-N
Target: Alpha-galactosidase (SINGLE PROTEIN), Escherichia coli
UniProt: P16551
Assay: Inhibition of Escherichia coli alpha-galactosidase using p-nitrophenyl-alpha-D-galactopyranoside as substrate preincubated for 1 hr followed by substrate addition measured after 10 mins by spectrophotometric method
Measurement: IC50 = 54640 nM (pChEMBL 4.260000228881836)
Descriptors: MW 163.17, ALogP -2.97, HBA 5, HBD 5, PSA 92.95, QED 0.31
Compound (SMILES): CC#C[C@@H](Cc1nnn[nH]1)c1ccc(OCc2ccc3sc(C)c(-c4ccc(OCCOC)cc4C)c3c2)cc1
InChIKey: LDSBSPJDRIKZDE-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at rat GPR40 assessed as increase in intracellular calcium flux by cell based FLIPR assay
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 552.7, ALogP 6.65, HBA 7, HBD 1, PSA 82.15, QED 0.15
Compound (SMILES): CC(=O)c1c(OCCCN2CCN(c3cccc(Br)c3)CC2)ccc2c(C)cc(=O)oc12
InChIKey: SAKSAVIEWZSKMA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor expressed in CHO-K1 cell membranes after 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 499.41, ALogP 4.66, HBA 6, HBD 0, PSA 62.99, QED 0.27
Compound (SMILES): CCOc1ccccc1CNC(=O)c1sc(Br)c2c1CCC(C)(C)C2
InChIKey: JPNUDHLFIFCNCG-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 422.39, ALogP 5.35, HBA 3, HBD 1, PSA 38.33, QED 0.71
Compound (SMILES): O=C(OC(C(F)(F)F)C(F)(F)F)N1CCC(CNS(=O)(=O)c2ccc(Cl)cc2)CC1
InChIKey: RLYMQNQYCHGICP-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human MAGL
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 482.83, ALogP 3.96, HBA 4, HBD 1, PSA 75.71, QED 0.64
Compound (SMILES): CC(C)OC(=O)N1CCC(CCCCCOc2ccc(C(=O)N(C)C)cc2)CC1
InChIKey: BLGZCKKNXGGFSV-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 404.55, ALogP 4.58, HBA 4, HBD 0, PSA 59.08, QED 0.57
Compound (SMILES): CC(=O)Oc1[nH]c2ccccc2c1-c1ccc(C)cc1
InChIKey: PEWUZJBZSZNFRJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His-tagged GSK3beta using GS-2 peptide as substrate in presence of [33P]gamma-ATP after 15 mins by microbeta counting method
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 265.31, ALogP 4.07, HBA 2, HBD 1, PSA 42.09, QED 0.71
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)CC(C)C6)n3)nc2)CC1
InChIKey: ZZBUMHLUAAJMOY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/ G1/S-specific cyclin-D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full length CDK1/Cyclin D3 expressed in baculovirus infected Sf9 insect cells using histone H1 substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 1920 nM (pChEMBL 5.71999979019165)
Descriptors: MW 504.59, ALogP 4.24, HBA 8, HBD 1, PSA 75, QED 0.42
Compound (SMILES): CC(C)n1cc(NC(=O)c2ccc(Nc3ccc4ccccc4c3)cc2)c(=O)n(CC(=O)N[C@H]2CC(=O)OC2O)c1=O
InChIKey: NZXOJGKUECLHSY-QASNXKAYSA-N
Target: Caspase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29466
Assay: Inhibition of caspase-1 in human THP1 cells assessed as decrease in LPS-induced IL-1beta secretion after overnight incubation by sandwich immunoassay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 571.59, ALogP 2.49, HBA 10, HBD 4, PSA 160.76, QED 0.23
Compound (SMILES): O=C(O)CCC(=O)N(C1CC1)[C@H]1c2ccccc2N(C(=O)c2ccc(OC(F)(F)F)cc2)[C@H]2CC[C@H]21
InChIKey: BWTYCMYHBBZDDQ-IZIIKQMZSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity at human CRTh2 expressed in HEK cells assessed as inhibition of DK-PGD2-mediated attenuation of forskolin-induced intracellular cAMP accumulation preincubated for 10 mins followed by forskolin stimulation measured after 10 to 60 mins by ELISA based chemiluminescence assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 502.49, ALogP 4.92, HBA 4, HBD 1, PSA 87.15, QED 0.58
Compound (SMILES): CC(C)NC1=CC(=O)C(c2ccccc2)=C(CC(=O)NCc2ccc(C(=N)N)cc2)C1=O
InChIKey: AMMVTBYUYICSEJ-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human factor 10a using N-alpha-benzyloxy-carbonyl-D-arginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride as substrate after 60 mins
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 430.51, ALogP 2.46, HBA 5, HBD 4, PSA 125.14, QED 0.29
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCC)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O)[C@]1(C)CCCC=CCCC[C@@](C)(NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(C)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N1)[C@@H](C)CC)C(N)=O
InChIKey: ZYDAFJIWJSHZGB-AHSPYXSFSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Inhibition of recombinant Leishmania infantum trypanothione reductase using T[S]2 as substrate preincubated for 5 mins followed by substrate and NADPH addition measured for 1 hr
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 1444.83
Compound (SMILES): CC(C)COc1ccccc1CNC(=O)c1c2c(c(Cl)n1C)CCC(C)(C)C2
InChIKey: AKPBGOZQZZJVAV-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 402.97, ALogP 5.16, HBA 3, HBD 1, PSA 43.26, QED 0.72
Compound (SMILES): COc1cccc2cc(C(=O)NCNC(=O)CCN(O)C=O)oc12
InChIKey: LMTOPUVETJLCPW-UHFFFAOYSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of MMP12 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.32, ALogP 0.48, HBA 6, HBD 3, PSA 121.11, QED 0.28
Compound (SMILES): O=C1C(F)CCCN1CC(O)Cn1c2ccc(F)cc2c2cc(F)ccc21
InChIKey: HGOQBSRIJKOSDE-UHFFFAOYSA-N
Target: Period circadian protein homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O15055
Assay: Per2 Assay: Compounds were screened by using a high-throughput circadian assay system as previously described in Zhang, E. E. et al. Cell, 2009, 139, 199-210. In brief, stable U20S reporter cells harboring Per2-dLuc were plated at a density of 30,000 cells/well in Corning 96-well, solid white, flat bottom, TC-treated microplates (Corning), and incubated for 48 hours at 37° C. in the presence of 5% CO2 in a medium of Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin (100 units/mL)-streptomycin (100 μg/mL). Compounds of formula I are solubilized in dimethylsulfoxide (DMSO), typically at a concentration of 2 mg/mL. DMSO stocks are then serially diluted in DMSO, typically diluting 3-fold for each dilution step. Following the 48 h period, cell culture medium is removed from plated cells and cells are synchronized with 200 μL/well of complete cell culture medium (described above), supplemented with 5 μM forskolin (Tocris) and 1 mM beetle luciferin (Promega). Immediately following synchronization, 1 μL of compound dilution is added to each well. Plates are sealed, shaken briefly, and gene expression was monitored by measuring luminescence (Tecan Infinite M200 or Tecan Infinite M200 Pro) continuously for a minimum of 3 days at 35° C. Raw luminescence data (counts) are first analyzed using Multicycle software (Actimetrics, Inc.) to determine the amplitude (amp), period, and phase (phz) for each compound concentration. The period length for control wells (i.e. no compound, DMSO only) should be 26-30 h. Amp data are then plotted against the logarithm compound concentration (M) and analyzed by nonlinear regression analysis to determine the EC50.
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 376.38, ALogP 3.39, HBA 3, HBD 1, PSA 45.47, QED 0.76
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N[C@@H]2CCN(S(C)(=O)=O)C2)nc(N2CCOCC2)n1
InChIKey: UOWGAUWLHMPTNI-CYBMUJFWSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His-tagged human PI3K p110beta/p85alpha expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 524.55, ALogP 1.44, HBA 11, HBD 1, PSA 127.6, QED 0.48
Compound (SMILES): CCOc1ccc(C(C)N2CCC(n3c(=O)[nH]c4ccccc43)CC2)cc1
InChIKey: ZOJROTRDOQRJLC-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human mu opioid receptor expressed in human USOS-beta-arrestin-hMOR-PathHunter cells incubated for 90 mins by beta-arrestin-2 enzyme fragment complementation assay
Measurement: EC50 = 1074 nM (pChEMBL 5.96999979019165)
Descriptors: MW 365.48, ALogP 4.13, HBA 4, HBD 1, PSA 50.26, QED 0.74