lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Clc1cc2cnn(-c3cnn(C4CCC4)c3)c2cc1C1CCN(C2COC2)CC1
InChIKey: XPKGIYJABSMIPH-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST tagged LRRK2 G2019S mutant catalytic domain (970 to 2527 residues) expressed in baculovirus expression system using fluorescein-labeled LRRKtide as substrate preincubated for 15 mins followed by substrate addition and measured after 90 mins by TR-FRET based Lanthascreen assay
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 411.94, ALogP 4.18, HBA 6, HBD 0, PSA 48.11, QED 0.65
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCCC(Nc3ncc(CNc4cc(C(F)(F)F)c(Cl)cn4)s3)C2)cc1
InChIKey: ALIURTYZQYAYDF-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 565.02, ALogP 5.66, HBA 7, HBD 3, PSA 99.25, QED 0.31
Compound (SMILES): O=c1c2cc(Br)ccc2n2c(=S)[nH]nc2n1CCc1ccccc1
InChIKey: POJBEZPPFIPGTF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of biotin-Ahx-CETFDPPLHSpTAI-NH2 binding to recombinant human full-length HA-EGFP-tagged Plk1 PBD expressed in HEK293A cells preincubated for 30 mins followed by biotin-Ahx-CETFDPPLHSpTAI-NH2 addition and measured after 1 hr by 3,3',5,5'-tetramethylbenzidine substrate based ELISA
Measurement: IC50 = 14740 nM (pChEMBL 4.829999923706055)
Descriptors: MW 401.29, ALogP 3.71, HBA 5, HBD 1, PSA 55.09, QED 0.53
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3ccc4[nH]nc(-c5cc6c(-c7cccnc7)cncc6[nH]5)c4n3)c2)C1
InChIKey: RSJOXHXTPXYUGS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 508.54, ALogP 5.47, HBA 6, HBD 2, PSA 99.27, QED 0.32
Compound (SMILES): O=C(Nc1ccccc1)[C@H]1CC[C@H](C(=O)/C(=N/O)Nc2ccc(F)c(Br)c2)CC1
InChIKey: ZUQBYJDYCBEATA-HDJSIYSDSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells using L-tryptophan as substrate measured after 48 hrs
Measurement: IC50 = 197 nM (pChEMBL 6.710000038146973)
Descriptors: MW 462.32, ALogP 4.8, HBA 4, HBD 3, PSA 90.79, QED 0.26
Compound (SMILES): O=C(c1ccc([S+]([O-])c2ccccc2)cc1)C1CCN(C(=O)c2cccc(O)c2)CC1
InChIKey: ZFCBEWJBSFKUJX-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL using 4-nitrophenylacetate as substrate incubated for 30 mins by microplate reader assay
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 433.53, ALogP 4.29, HBA 4, HBD 1, PSA 80.67, QED 0.48
Compound (SMILES): COc1ccc(/C=C2\C[C@]3(C)[C@H]4C[C@@H](O)[C@@H]5[C@@H]([C@@]6(C)CCCC(C)(C)O6)CC[C@@]5(C)[C@]4(C)CC[C@H]3C(C)(C)\C2=N\NC(=N)N)cc1
InChIKey: GLGMFXYJYWQKOC-AIXZGNJPSA-N
Target: Hypoxia-inducible factor 1-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q16665
Assay: Inhibition of hypoxia-induced HIF1alpha transcriptional activity in human Hep3B cells co-transfected with luciferase reporter plasmid containing six copies of HREs and pRL-CMV vector assessed as reduction in luciferase activity incubated for 24 hrs under hypoxic condition by HRE-dependent dual luciferase reporter gene assay
Measurement: IC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 632.93, ALogP 7.92, HBA 5, HBD 4, PSA 112.95, QED 0.15
Compound (SMILES): Nc1cccc(-c2nc3sccn3c2-c2ccnc(NCCCCNS(=O)(=O)c3ccc(Cl)cc3)n2)c1
InChIKey: MITBNOSFWBXKJN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant (unknown origin)
Measurement: IC50 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 554.1, ALogP 4.93, HBA 9, HBD 3, PSA 127.3, QED 0.17
Compound (SMILES): Nc1nccc(Sc2cnc(N3CCC4(CCC[C@H]4N)CC3)cn2)c1Cl
InChIKey: CQASZSQCUYWGME-CYBMUJFWSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of 6x-histidine tagged human SHP2 (Met1-L525 residues) expressed in Escherichia coli BL21 Star (DE3) using IRS1_pY1172(dPEG8)pY122 incubated for 30 mins by fluorescence based DIFMUP assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 390.94, ALogP 3.36, HBA 7, HBD 2, PSA 93.95, QED 0.83
Compound (SMILES): c1ccc2cc(Nc3n[nH]c4cccnc34)ccc2c1
InChIKey: FAUFNAAZZSERRI-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Positive allosteric modulator activity at human mGlu4 receptor/Gqi5 in presence of EC20 glutamate by calcium mobilization assay
Measurement: EC50 = 403 nM (pChEMBL 6.389999866485596)
Descriptors: MW 260.3, ALogP 3.85, HBA 3, HBD 2, PSA 53.6, QED 0.58
Compound (SMILES): Fc1cccc(-c2cncc3[nH]c(-c4n[nH]cc4C#Cc4cncc(OC5CCNCC5)c4)nc23)c1
InChIKey: RVRKXCLGPUNFPE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 479.52, ALogP 4.08, HBA 6, HBD 3, PSA 104.4, QED 0.34
Compound (SMILES): Cc1noc2c1-c1ccc(-c3cnn(C)c3)cc1N(c1ccc(C#N)cc1)CC2CC(N)=O
InChIKey: MQKDPPYZXQQYDW-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His/FLAG-tagged BRD4 BD1 (unknown origin) using histone H4-TetraAcetylated-biotin peptide as substrate incubated for 20 mins by AlphaLISA assay
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 438.49, ALogP 4.03, HBA 7, HBD 1, PSA 113.97, QED 0.51
Compound (SMILES): COc1cccc2c1c1c(n2Cc2ccc(Cl)cc2)C(C(=O)O)=NCC1
InChIKey: ARHMVMKIRPRSJS-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX1 using [1-14C]AA as substrate preincubated for 20 mins followed by substrate addition and measured for 30 sec by thin layer chromatography analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 368.82, ALogP 3.78, HBA 4, HBD 1, PSA 63.82, QED 0.76
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: IDNHSICEMKTUAB-NLVDHLGFSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]Tyr3-neurotensin from human recombinant NTS1 stably expressed in CHO-K1 cell membranes incubated for 60 mins by gamma counter analysis
Measurement: Ki = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 1646.91
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CCC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: HWGGKSUESBGTAA-UMYBCCRSSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from mu opioid receptor in rat brain membranes incubated for 45 mins by liquid scintillation counting method
Measurement: Ki = 2.48 nM (pChEMBL 8.609999656677246)
Descriptors: MW 445.52, ALogP 0.51, HBA 7, HBD 4, PSA 134.35, QED 0.48
Compound (SMILES): C/C(=N\CCO)c1c(O)c2ccccc2oc1=O
InChIKey: MMGMQMKACABQDU-RIYZIHGNSA-N
Target: Myosin-2 (SINGLE PROTEIN), Bos taurus
UniProt: Q9BE41
Assay: Inhibition of actin-activated bovine heart muscle myosin 2 assessed as phosphate level incubated for 6 to 24 mins by spectrophotometric method
Measurement: IC50 = 92000 nM (pChEMBL 4.039999961853027)
Descriptors: MW 247.25, ALogP 1.3, HBA 5, HBD 2, PSA 83.03, QED 0.63
Compound (SMILES): Cc1nc(N2CCC(F)(F)CC2)c(C(=O)Nc2ccnc(S(N)(=O)=O)c2)cc1C#CC1CC1
InChIKey: UQGRTUXRGBIUNG-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y9
Assay: Inhibition of human Nav1.8 expressed in HEK293 cells by whole cell patch clamp assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 475.52, ALogP 2.68, HBA 6, HBD 2, PSA 118.28, QED 0.66
Compound (SMILES): COc1ccc(C(=O)N2CCC[C@H](c3ccnc4ncnn34)C2)cc1
InChIKey: JCZAUBCLCFIOLN-AWEZNQCLSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of 6xHis-tagged human recombinant PDE2A expressed in Sf9 cells in presence of [3H]-cGMP and cGMP incubated for 40 mins by scintillation counting method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 337.38, ALogP 2.15, HBA 6, HBD 0, PSA 72.62, QED 0.73
Compound (SMILES): CC(C)(C)N1CCN(C(=O)c2ccc(-c3cnc(N)c(-c4ccc(C(F)(F)F)cc4)n3)cc2)CC1
InChIKey: MPJVEQUTYMMVFV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by IonWorks patch clamp electrophysiology method
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 483.54, ALogP 4.97, HBA 5, HBD 1, PSA 75.35, QED 0.57
Compound (SMILES): N#Cc1cccc(NC(=O)N2CCOc3ccc(-c4ccncc4)cc3C2)c1
InChIKey: ZMKWHQJUHAUIFS-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 370.41, ALogP 4.05, HBA 4, HBD 1, PSA 78.25, QED 0.74
Compound (SMILES): Cc1nn(-c2cc(N[C@H]3CC[C@H](O)CC3)c3c(=O)[nH]c(CO)cc3c2)c2c1C(=O)CC(C)(C)C2
InChIKey: SSQSXISQRCWETH-RUCARUNLSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Inhibition of FITC-GDA binding to human HSP90-beta incubated for 2 hrs by fluorescence polarization assay
Measurement: IC50 = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 464.57, ALogP 3.39, HBA 7, HBD 4, PSA 120.24, QED 0.47
Compound (SMILES): CCNc1cc(Nc2ccc(F)c(Cl)c2)c2cc(C(=O)O)[nH]c2c1
InChIKey: MHUNXTCTIMUGPZ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 assessed as reduction in kynurenine formation using L-tryptophan as substrate incubated for 45 mins by microplate reader assay
Measurement: IC50 = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 347.78, ALogP 4.83, HBA 3, HBD 4, PSA 77.15, QED 0.53
Compound (SMILES): CC/C(=C(/c1ccc(/C=C/C(=O)O)cc1)c1cc2ccccc2[nH]1)c1ccc(C(F)(F)F)cc1Cl
InChIKey: UVRSTTKJPOUOQH-USYAYNFISA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to estrogen receptor (unknown origin)
Measurement: IC50 = 0.98 nM (pChEMBL 9.010000228881836)
Descriptors: MW 495.93, ALogP 8.31, HBA 1, HBD 2, PSA 53.09, QED 0.21
Compound (SMILES): CC1(C)CC(c2cc(-c3c[nH]c(=O)[nH]c3=O)nnc2Cl)C1
InChIKey: CNUUNMWDKZAFRY-UHFFFAOYSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of human C-terminal 6His-tagged CD73 (1 to 547 residues) expressed in HEK293F cells using 2 uM AMP as substrate by rapidfire mass spectrometry assay
Measurement: IC50 < 62 nM (pChEMBL 7.208000183105469)
Descriptors: MW 306.75, ALogP 2.08, HBA 4, HBD 2, PSA 91.5, QED 0.89
Compound (SMILES): Cc1ccc(Oc2ccc(/C=C3\SC(=O)N(c4cccc(OCCCCCN5CCN(C)CC5)c4)C3=O)cc2)cc1
InChIKey: WHXXWVOLDCVUKL-SXBRIOAWSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Allosteric inhibition of IKKbeta (unknown origin) using 5FAM-GRHDSGLDSMK-NH2 as substrate pretreated for 10 mins followed measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 2730 nM (pChEMBL 5.559999942779541)
Descriptors: MW 571.74, ALogP 6.82, HBA 7, HBD 0, PSA 62.32, QED 0.18
Compound (SMILES): Clc1ccc2c(N3CCCCCC3)cc[n+](Cc3ccccc3)c2c1.[Br-]
InChIKey: CVUZJARIIHMFEI-UHFFFAOYSA-M
Target: Choline kinase alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35790
Assay: Binding affinity to human CKalpha1 assessed as dissociation constant by spectroflurometry
Measurement: Kd = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 351.9, ALogP 5.21, HBA 1, HBD 0, PSA 7.12, QED 0.59
Compound (SMILES): Cc1cc(C(=O)O)nc(N2CCC(Oc3ccccc3C(F)(F)F)CC2)n1
InChIKey: CBVSQGKWBDWFHM-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Displacement of [3H]-all-trans-retinol from biotinylated human urine derived RBP4 measured after 16 hrs by scintillation proximity assay
Measurement: IC50 = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 381.35, ALogP 3.55, HBA 5, HBD 1, PSA 75.55, QED 0.87
Compound (SMILES): COC(=O)N(C)c1c(N)nc(-c2nc(Cc3ccccc3F)n3ncccc23)nc1N
InChIKey: JOHZPMNOKLTTTM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 16100 nM (pChEMBL 4.789999961853027)
Descriptors: MW 422.42, ALogP 2.28, HBA 9, HBD 2, PSA 137.55, QED 0.51
Compound (SMILES): Nc1cc([C@H](CCNCc2ccccn2)c2ccccc2)c2nn[nH]c2n1
InChIKey: WGDPAPUWFOJAGX-MRXNPFEDSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay
Measurement: IC50 = 616 nM (pChEMBL 6.210000038146973)
Descriptors: MW 359.44, ALogP 2.64, HBA 6, HBD 3, PSA 105.4, QED 0.44
Compound (SMILES): COc1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: YTKAFKXVZBIBGM-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 719.3 nM (pChEMBL 6.139999866485596)
Descriptors: MW 428.49, ALogP 0.91, HBA 6, HBD 4, PSA 156.69, QED 0.49
Compound (SMILES): NC(=O)[C@@H](c1ccccc1)N(C(=O)c1ccccc1)[C@@H]1CCc2c(F)cc(F)cc21
InChIKey: DYHUHIAITPIDLZ-FGZHOGPDSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 transfected in HEK293T cells assessed as reduction in menthol-induced calcium influx measured after 60 mins by Fluo-4 AM dye based fluorescence analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 406.43, ALogP 4.32, HBA 2, HBD 1, PSA 63.4, QED 0.69
Compound (SMILES): CO[C@@H]1[C@@H](O)C[C@H]2O[C@]1(C)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: OSJFVOAURBIGTC-GNIPNZNASA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKCtheta (unknown origin) by HTRF assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 453.5, ALogP 4.13, HBA 6, HBD 2, PSA 77.65, QED 0.4
Compound (SMILES): C[C@H](Nc1c(Cl)cnc2ccc(-c3cnc(C(C)(C)O)nc3)cc12)c1ccccc1
InChIKey: WFACESJCRDGXRJ-HNNXBMFYSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Displacement of fluorescent labeled probe from human recombinant His-tagged TNFalpha (77 to 233 residues) expressed in Escherichia coli preincubated for 1 hr followed by fluorogenic probe addition and measured after 3 hrs by HTRF assay
Measurement: IC50 = 943 nM (pChEMBL 6.03000020980835)
Descriptors: MW 418.93, ALogP 5.75, HBA 5, HBD 2, PSA 70.93, QED 0.43
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N/N=C(\CS(=O)(=O)c2ccccc2)c2cc3ccccc3oc2=O)cc1
InChIKey: QWKJONKITDUSDD-YYADALCUSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 1537 nM (pChEMBL 5.809999942779541)
Descriptors: MW 525.56, ALogP 2.05, HBA 8, HBD 2, PSA 165.97, QED 0.21
Compound (SMILES): Cc1ccc(C(=O)NC2CC2)cc1-n1ccnc(N[C@@H](c2ccccc2)[C@@H](C)CN2CCCCC2)c1=O
InChIKey: ZHDPCEDWVBEHRX-WXVAWEFUSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38alpha MAPK (unknown origin)
Measurement: IC50 = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 499.66, ALogP 4.71, HBA 6, HBD 2, PSA 79.26, QED 0.45
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CCN(C3CC3)CC2)cc1)c1ccccc1
InChIKey: ZYOFNMPBJCPWJW-FJISBNMDSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding affinity to ERRgamma (unknown origin) by TR-FRET assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 453.63, ALogP 6.47, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): COc1cc(OCc2ccnc(Nc3cn(C)nn3)n2)cc2sc(N[C@H]3CCCC[C@@H]3O)nc12
InChIKey: YNMOKWHHWDXEFZ-HOTGVXAUSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of AlexaFluor-labeled tracer 236 binding to recombinant human His-tagged CSF1R (538 to 910 residues) preincubated for 20 mins followed by Eu-labeled anti-His antibody addition and measured after 90 mins by FRET based LanthaScreen assay
Measurement: IC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 482.57, ALogP 3.26, HBA 12, HBD 3, PSA 132.13, QED 0.34
Compound (SMILES): CC[C@H](C)C(=O)N1CCC(CC(=O)Nc2ccc(OC(F)(F)F)c(F)c2)CC1
InChIKey: GBWBRIAGOMFVIA-LBPRGKRZSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 3.14 nM (pChEMBL 8.5)
Descriptors: MW 404.4, ALogP 4.34, HBA 3, HBD 1, PSA 58.64, QED 0.72
Compound (SMILES): O=P(O)(O)CP(=O)(O)OC[C@H]1O[C@@H](n2cnc3c(NCc4ccccc4)nc(N4CCCC4)nc32)[C@H](O)[C@@H]1O
InChIKey: KUXIRIUARNERMJ-QTQZEZTPSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 584.46, ALogP 0.99, HBA 12, HBD 6, PSA 212.62, QED 0.18
Compound (SMILES): O=C1CCSC[C@@H](C(=O)Nc2cccc(Cl)c2)N1
InChIKey: HIFTXEMJTYXXDX-JTQLQIEISA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31423
Assay: Positive allosteric modulation of rat mGlu4 receptor expressed in HEK293 cells co- expressing GIRK channel by thallium mobilization assay
Measurement: EC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 284.77, ALogP 1.9, HBA 3, HBD 2, PSA 58.2, QED 0.87
Compound (SMILES): CC/C(=C(/c1ccc(/C=C/C(=O)O)cc1)c1cc2ccccc2[nH]1)c1cc(Cl)ccc1Cl
InChIKey: RAZCHHKYEOCEJP-USYAYNFISA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to estrogen receptor (unknown origin)
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 462.38, ALogP 7.94, HBA 1, HBD 2, PSA 53.09, QED 0.23
Compound (SMILES): O=C(NCCCN1CCCC1)c1cncc(-c2ccccc2N2CCN(CCc3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: HGADSNNQOFDZDI-UHFFFAOYSA-N
Target: N-lysine methyltransferase SMYD2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRG4
Assay: Inhibition of SMYD2 (unknown origin)
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 566.58, ALogP 5.64, HBA 5, HBD 1, PSA 51.71, QED 0.32
Compound (SMILES): O=C(O)C1CCCN1C(=O)CCN1CCCc2ccccc21
InChIKey: PJWHESRYVASPCJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from muscarinic M4 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 891.25 nM (pChEMBL 6.050000190734863)
Descriptors: MW 302.37, ALogP 1.9, HBA 3, HBD 1, PSA 60.85, QED 0.92
Compound (SMILES): O=C(C[C@@H]1Cc2cc(Cl)c3[nH]ncc3c2CN(CC(F)(F)F)C1=O)N1CCC(n2c(=O)[nH]c3ccccc32)CC1
InChIKey: RJSHCACLCUFPRJ-INIZCTEOSA-N
Target: Calcitonin gene-related peptide type 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16602
Assay: Antagonist activity at human CGRP receptor
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 574.99, ALogP 4.18, HBA 5, HBD 2, PSA 107.09, QED 0.38
Compound (SMILES): O=C(O)Cc1ccccc1NC(=O)c1cccc(-c2ccc(Cl)c(O[C@@H]3CCCNC3)c2F)c1
InChIKey: GFZGZLKOWGFBSB-LJQANCHMSA-N
Target: Succinate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXA5
Assay: Antagonist activity at human SUCNR1 expressed in human CHEM1 cells incubated for 60 mins in presence of [35S]GTPgammaS by scintillation proximity assay
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 482.94, ALogP 5.16, HBA 4, HBD 3, PSA 87.66, QED 0.43
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCN)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)NC(C)(C)C(=O)N[C@@H](Cc1ccc(Br)cc1)C(=O)O
InChIKey: IUMIWRMQDWJGNU-IDIMAXLMSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Activation of APJ receptor (unknown origin) expressed in Chem-5 cells assessed as stimulation of Ca2+ mobilization by Calcium 6-GF dye based fluorescence based assay
Measurement: EC50 = 4.898 nM (pChEMBL 8.3100004196167)
Descriptors: MW 2935.31
Compound (SMILES): COCCS(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccccc3)N2)c1O
InChIKey: DYFXQMZMYIFFKC-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 423.88, ALogP 2.1, HBA 7, HBD 3, PSA 117.09, QED 0.61
Compound (SMILES): CC(Nc1c(Cl)cnc2ccc(-c3cnc(C(C)(C)O)nc3)cc12)c1cccc(F)c1
InChIKey: OYECHCQRUDNDTI-UHFFFAOYSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Displacement of fluorescent labeled probe from human recombinant His-tagged TNFalpha (77 to 233 residues) expressed in Escherichia coli preincubated for 1 hr followed by fluorogenic probe addition and measured after 3 hrs by HTRF assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 436.92, ALogP 5.88, HBA 5, HBD 2, PSA 70.93, QED 0.41
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2cc3c(N[C@H](CO)c4ccccc4)ncnc3[nH]2)cc1
InChIKey: KKROQQUFNCLGRA-LJQANCHMSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma33P]ATP by radiometric HotSpot assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 423.5, ALogP 3.14, HBA 6, HBD 4, PSA 120, QED 0.36
Compound (SMILES): CC(C)(O)COc1ccc(C(F)(F)F)cc1NC(=O)c1cc(C(C)(C)C)nn1C[C@H]1CCCO1
InChIKey: KUFBHTSQDQVKLS-MRXNPFEDSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 expressed in mouse AtT20 cells assessed as activation of G-protein gated inwardly rectifying K+ channels measured every 2 sec for 2 mins by FLIPR membrane potential assay
Measurement: EC50 = 6760 nM (pChEMBL 5.170000076293945)
Descriptors: MW 483.53, ALogP 4.78, HBA 6, HBD 2, PSA 85.61, QED 0.59
Compound (SMILES): CCC/N=C1\S/C(=C\c2ccc(O)c(Cl)c2)C(=O)N1C1CCOCC1
InChIKey: CVUOUVVVXQNIRL-JTHVCAJSSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Immunomodulatory activity at human S1PR1 expressed in CHO-K1 EDG1 beta-arrestin cells assessed as stimulation of beta-arrestin recruitment incubated for 90 mins at 37 degC followed by incubated for 15 mins in room temperature by pathhunter beta-arrestin assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 380.9, ALogP 3.91, HBA 5, HBD 1, PSA 62.13, QED 0.8
Compound (SMILES): CC(C)c1noc(N2CCC(Oc3cc(N4CCc5cc(N6CCCNS6(=O)=O)ccc54)ncn3)CC2)n1
InChIKey: CFABNFPFYHNDOQ-UHFFFAOYSA-N
Target: Glucose-dependent insulinotropic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDV5
Assay: Agonist activity at human GPR119 expressed in CHO cells co-expressing cyclic AMP response element incubated for 2 hrs by steady-glo luciferase assay
Measurement: EC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 540.65, ALogP 2.77, HBA 10, HBD 1, PSA 129.82, QED 0.5
Compound (SMILES): CN(CCc1ccccc1)c1nc(C(=O)NCC(F)(F)F)cc(N2CCOCC2)n1
InChIKey: HCXZFZMNFBBXFN-UHFFFAOYSA-N
Target: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ20
Assay: Inhibition of full length human NAPE-PLD expressed in HEK293T cell lysate using PED6 as substrate preincubated for 30 mins followed by substrate addition and measured at 2 mins interval for 1 hr by tecan-plate reader analysis
Measurement: IC50 = 33113.11 nM (pChEMBL 4.480000019073486)
Descriptors: MW 423.44, ALogP 2.28, HBA 6, HBD 1, PSA 70.59, QED 0.74
Compound (SMILES): CCCCCCCCCCCCNC=O
InChIKey: TYCXRAVZVQSHSC-UHFFFAOYSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Inhibition of human mEH using CMNGC as substrate preincubated for 5 mins followed by substrate addition and measured at 30 secs interval for 10 mins by fluorescence assay
Measurement: IC50 = 15100 nM (pChEMBL 4.820000171661377)
Descriptors: MW 213.37, ALogP 3.65, HBA 1, HBD 1, PSA 29.1, QED 0.39
Compound (SMILES): CNc1nc(OCCOC)nc2c1[nH]c(=O)n2Cc1ccccc1
InChIKey: OSILWVXKFRDCIL-UHFFFAOYSA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Binding affinity to MTH1 in human K562 cells assessed as thermal stabilization preincubated for 30 mins followed by heating at 52 degree C for 3 mins by CETSA-based Western blot analysis
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 329.36, ALogP 1.23, HBA 7, HBD 2, PSA 94.06, QED 0.63
Compound (SMILES): Cc1ccncc1C(=O)Nc1cccc2c1N(Cc1ccc(OC3CCNCC3)cc1)CCC2
InChIKey: AFSOEKUDDZIBHR-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant LSD1 using fluorogenic ADHP based substrate preincubated for 30 mins followed by substrate addition measured after 10 mins by horseradish peroxidase coupled fluorescence assay
Measurement: IC50 = 1.56 nM (pChEMBL 8.8100004196167)
Descriptors: MW 456.59, ALogP 4.73, HBA 5, HBD 2, PSA 66.49, QED 0.56
Compound (SMILES): CCCC[C@H](CN)Nc1nc(N)nc2cccnc12
InChIKey: ATFVZNWHRHNNNN-SECBINFHSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 in human cryopreserved PBMC assessed as inhibition of IL-12p40 production measured after 24 hrs
Measurement: EC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 260.35, ALogP 1.54, HBA 6, HBD 3, PSA 102.74, QED 0.73
Compound (SMILES): COCCNc1oc(-c2ccc(N(C)Cc3ccc(Cl)cc3)cc2)nc1C#N
InChIKey: REPYPLJBEDYASE-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group D member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P20393
Assay: Inverse agonist activity at Rev-Erb alpha LBD (unknown origin) by FRET assay
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 396.88, ALogP 4.56, HBA 6, HBD 1, PSA 74.32, QED 0.56
Compound (SMILES): NC(=O)[C@@H](c1ccccc1)N(C(=O)c1ccccc1)[C@@H]1COc2ccccc21
InChIKey: WWINCCOXBCZASU-TZIWHRDSSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 transfected in HEK293T cells assessed as reduction in menthol-induced calcium influx measured after 60 mins by Fluo-4 AM dye based fluorescence analysis
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 372.42, ALogP 3.49, HBA 3, HBD 1, PSA 72.63, QED 0.75
Compound (SMILES): COc1cc(C(=O)N2CCC(O)C(C)C2)cc2nc(NC3(c4cccc(Cl)c4)CCC3)oc12
InChIKey: XAHDPALRFABLCC-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Inhibition of purified human plasma thrombin using Boc-Asp(OBzl)-Pro-Arg-AMC substrate incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 469.97, ALogP 4.82, HBA 6, HBD 2, PSA 87.83, QED 0.56
Compound (SMILES): CSc1ccc(-c2cc3ncnc(NCC(=O)O)c3s2)cc1
InChIKey: YQQOYSLULNYKGR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17B (SINGLE PROTEIN), Homo sapiens
UniProt: O94768
Assay: Binding affinity to C-terminal nano-luciferase tagged STK17B (unknown origin) expressed in HEK293 cells incubated for 2 hrs by nano-BRET assay based cellular target engagement assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 331.42, ALogP 3.58, HBA 6, HBD 2, PSA 75.11, QED 0.7
Compound (SMILES): N=C(N)Nc1ccc(CC(=O)Oc2ccc(-c3ccccc3)cc2)cc1
InChIKey: SBBCAXXGVMAGDY-UHFFFAOYSA-N
Target: Acid ceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q13510
Assay: Inhibition of human acid ceramidase
Measurement: IC50 = 52000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 345.4, ALogP 3.81, HBA 3, HBD 3, PSA 88.2, QED 0.28
Compound (SMILES): Fc1ccc(CNc2nc(Cl)nc3cc(-c4cccs4)ccc23)cc1F
InChIKey: IIFSHMRLQNEOMD-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 assessed as reduction in PGE2 production using 10 uM arachidonic acid as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured after 20 mins by ELISA
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 387.84, ALogP 5.9, HBA 4, HBD 1, PSA 37.81, QED 0.44
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)NC1CCN(C(=O)C2CCOC2)CC1
InChIKey: ZKPYTUBYBQCEMB-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 401.39, ALogP 2.73, HBA 4, HBD 2, PSA 79.9, QED 0.81
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4cccnc34)ccc12
InChIKey: IMDIQNUECOXRNB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Positive allosteric modulator activity at human mGlu4 receptor/Gqi5 in presence of EC20 glutamate by calcium mobilization assay
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): COc1ccc(CCCC(C)(C)C)c(-c2ccc(COc3cccc(C(CC(=O)O)C4CC4)c3)cc2)c1
InChIKey: BZZFJGXGVNOTIU-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human GPR40 expressed in CHO cells incubated for 60 mins by FLIPR based Ca2+ mobilization assay
Measurement: EC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 500.68, ALogP 8.28, HBA 3, HBD 1, PSA 55.76, QED 0.27
Compound (SMILES): Cc1ccc([C@@H](Oc2ccc(C(=O)O[C@H]3CCCN(C(=O)[C@H]4COC(=O)C4)C3)cc2)[C@H](C)NC(=O)C(F)(F)F)cc1
InChIKey: RCJSYCYPQJPBNO-XDCBZQCGSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at human glucocorticoid receptor in PBMC assessed as inhibition of LPS-induced TNFalpha release
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 576.57, ALogP 3.89, HBA 7, HBD 1, PSA 111.24, QED 0.47
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)Cn2nc3cnc(C)cn3c2=O)cc1
InChIKey: DAEYHMKWNKIYFC-ZDUSSCGKSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 325.37, ALogP 1.39, HBA 6, HBD 1, PSA 81.29, QED 0.79
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)C(OC(=O)c4ccc(Cl)cc4)C(C)(C)C)cc3F)c2cc1OC
InChIKey: JEVDNCWECKJBCA-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin) using poly (Glu, Tyr) 4:1 as substrate measured after 30 mins by HTRF assay
Measurement: IC50 = 7.43 nM (pChEMBL 8.130000114440918)
Descriptors: MW 567.01, ALogP 7.05, HBA 7, HBD 1, PSA 95.98, QED 0.23
Compound (SMILES): COC(=O)c1ccc(N(Cc2ccc(C3CCCCC3)nc2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: RYBCPRABHVSVDN-OAQYLSRUSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Mus musculus
UniProt: P42227
Assay: Inhibition of oligonucleotide [32P]-labelled 5'-AGCITCATTTCCCGTAAATCCCTA probe binding to STAT3 SH2 domain in mouse NIH3T3/v-Src nuclear extract preincubated for 30 mins followed by hSIE probe addition by EMSA analysis
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 653.63, ALogP 5.31, HBA 7, HBD 1, PSA 117.11, QED 0.15
Compound (SMILES): CN1CCCN(C(=O)c2ccc(-c3cnc(N)c(-c4ccc(C(F)(F)F)cc4)n3)cc2)CC1
InChIKey: JKGSEXNAJXBRDM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by IonWorks patch clamp electrophysiology method
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 455.48, ALogP 4.19, HBA 5, HBD 1, PSA 75.35, QED 0.64
Compound (SMILES): Cc1ccc(NC(=O)[C@H]2CC[C@H](Cn3c(=O)c4c(C)cccc4n(Cc4cccc(C(F)(F)F)c4C#N)c3=O)CC2)cn1
InChIKey: HOSHPNDTAUJRNF-HZCBDIJESA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of human TNKS1 incubated for 1 to 2 hrs by fluorescence polarization assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 589.62, ALogP 5.56, HBA 7, HBD 1, PSA 109.78, QED 0.32
Compound (SMILES): C[C@H](C(=O)Nc1ccc(Cl)cc1)[C@H]1CC[C@]2(CC1)COc1cc(C(F)(F)F)ccc12
InChIKey: WPNANUSCDOZUBH-DFFLPILJSA-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 437.89, ALogP 6.45, HBA 2, HBD 1, PSA 38.33, QED 0.6
Compound (SMILES): Cc1cccc(/C=N/NC(=O)N2CCN(c3ccccn3)CC2)c1
InChIKey: HCMDTJKJOPROCK-XSFVSMFZSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1 using MOCA-SEV-NL-DAEFR-DNP-RR as substrate preincubated with substrate followed by enzyme addition by FRET assay
Measurement: IC50 = 4370 nM (pChEMBL 5.360000133514404)
Descriptors: MW 323.4, ALogP 2.26, HBA 4, HBD 1, PSA 60.83, QED 0.7
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)C(OC(=O)c4ccc5ccccc5c4)C(C)(C)C)cc3F)c2cc1OC
InChIKey: LQQPMQJXLIYZBI-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin) using poly (Glu, Tyr) 4:1 as substrate measured after 30 mins by HTRF assay
Measurement: IC50 = 46.87 nM (pChEMBL 7.329999923706055)
Descriptors: MW 582.63, ALogP 7.55, HBA 7, HBD 1, PSA 95.98, QED 0.19
Compound (SMILES): C#Cc1nc(Nc2ccc3c(c2)C(=O)N(C)CC3)nc2[nH]cnc12
InChIKey: BMTCXQSTPVRURZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Nek2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51955
Assay: Inhibition of human recombinant full length His-tagged NEK2 expressed in baculovirus expression system assessed as inhibition of substrate phosphorylation using peptide 11 as substrate measured after 30 mins in presence of 30 uM ATP by caliper EZ reader analysis
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 318.34, ALogP 1.71, HBA 5, HBD 2, PSA 86.8, QED 0.7
Compound (SMILES): NC(=O)/C=C/c1cc(C(F)(F)F)cc2c(=O)nc(N3CCN(CC4CCCCC4)CC3)sc12
InChIKey: BNVSZORMQRZHFC-VOTSOKGWSA-N
Target: Decaprenylphosphoryl-beta-D-ribose oxidase (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: P9WJF1
Assay: Inhibition of Mycobacterium tuberculosis DprE1 expressed in Escherichia coli BL21 (DE3) cells assessed as formation of resorufin using FPR as substrate by Amplex Red hydrogen/peroxidase coupled assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 480.56, ALogP 3.88, HBA 6, HBD 1, PSA 79.53, QED 0.66
Compound (SMILES): C[C@H]1[C@@H]2C[C@@]3(O[C@H](CCC3(C)C)CC(=O)O[C@@H](CO)CC(=O)O2)O[C@@H]1CCCCc1cccc2cc(O)ccc12
InChIKey: HKRJMFZJHJZRJJ-ZCOUFJIGSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Mus musculus
UniProt: P20444
Assay: Displacement of [3H]-PDBu from PKCalpha C1A domain in CD-1 mouse brain cytosol
Measurement: Ki = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 554.68, ALogP 5.19, HBA 8, HBD 2, PSA 111.52, QED 0.37
Compound (SMILES): O=P(O)(O)c1c2c(c(P(=O)(O)O)c3c1[C@H]1C[C@@H]3c3cc4c(cc31)[C@H]1C[C@@H]4c3ccccc31)[C@H]1C[C@@H]2c2cc3c(cc21)[C@H]1C[C@@H]3c2ccccc21
InChIKey: WWDNUOWSRJTGEQ-FCODNRGNSA-N
Target: Alpha-synuclein (SINGLE PROTEIN), Homo sapiens
UniProt: P37840
Assay: Binding affinity to human alpha-synuclein (1-140 residues) expressed in Escherichia coli BL21(DE3) assessed as first dissociation constant by mass-spectrometry
Measurement: Kd = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 694.66, ALogP 7.22, HBA 2, HBD 4, PSA 115.06, QED 0.15
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3cncc(C(=O)O)c3)oc12
InChIKey: CRLCUIGNIXBPIV-UHFFFAOYSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 using 7-ethoxyresorufin as substrate after 35 mins in presence of NADP+ by EROD assay
Measurement: IC50 = 30.1 nM (pChEMBL 7.519999980926514)
Descriptors: MW 407.38, ALogP 3.73, HBA 7, HBD 1, PSA 108.09, QED 0.5
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3ccc4[nH]nc(-c5cc6cnccc6[nH]5)c4n3)c2)C1
InChIKey: SUTNENZRJYKUCC-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 431.45, ALogP 4.4, HBA 5, HBD 2, PSA 86.38, QED 0.44
Compound (SMILES): CCOC(=O)C(CC(C)C)Nc1nc2nn(C)cc2c2nc(-c3ccco3)nn12
InChIKey: VWCFLJSZVPXXPB-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]-HEMADO from human A3 receptor expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 397.44, ALogP 2.66, HBA 10, HBD 1, PSA 112.37, QED 0.47
Compound (SMILES): O=C(O)CSc1ncnc2sc(-c3cc4ccccc4s3)cc12
InChIKey: RRIRDIKTUQVZCW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Binding affinity to STK17A (unknown origin) by KINOMEscan scanMAX assay
Measurement: Kd = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): C#Cc1cc(CC(P(=O)(OC(C)C)OC(C)C)P(=O)(OC(C)C)OC(C)C)cc(C(C)(C)C)c1
InChIKey: ZHCATCPBHSGHKT-UHFFFAOYSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Induction of degradation of Flag-tagged human HMGCR-dCat-ELuc membrane domain (1 to 499 residues) expressed in HEK293 cells assessed as reduction in HMGCR-dCat-Eluc protein level after 4 hrs by luciferase reporter assay
Measurement: EC50 = 3540 nM (pChEMBL 5.449999809265137)
Descriptors: MW 514.58, ALogP 7.92, HBA 6, HBD 0, PSA 71.06, QED 0.21
Compound (SMILES): C[C@H](c1ccc2ncccc2c1)c1nnc2sc(-c3cnn(C)c3)nn12
InChIKey: AMVSPCWTSDZDPI-LLVKDONJSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using poly Glu-Tyr as substrate preincubated for 10 mins followed by ATP addition by phosphoenolpyruvate/pyruvate kinase/lactate dehydrogenase coupled radiometric assay
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 361.43, ALogP 3.29, HBA 8, HBD 0, PSA 73.79, QED 0.49
Compound (SMILES): CN1CCN(c2ccnc3[nH]c(-c4n[nH]c5ccc(-c6cncc(NC(=O)c7ccccc7)c6)nc45)cc23)CC1
InChIKey: RAHJKORHPROBCB-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 529.61, ALogP 4.57, HBA 7, HBD 3, PSA 118.72, QED 0.3
Compound (SMILES): CC(C)N(Cc1ccc(C(=O)NO)cc1)C(=O)c1c(F)c(F)c(F)c(F)c1F
InChIKey: HTDWCWRHHQCVJF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant full length human HDAC3 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 402.32, ALogP 3.55, HBA 3, HBD 2, PSA 69.64, QED 0.26
Compound (SMILES): O=C(O)CNC(=O)c1ncc(C#CCOc2ccc(F)cc2)cc1O
InChIKey: DLINBZMNJDYZFD-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of FITC-HIF1alpha (556 to 574 residues) binding to PHD2 (181 to 426 residues) (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 344.3, ALogP 1.17, HBA 5, HBD 3, PSA 108.75, QED 0.7
Compound (SMILES): Cc1ccncc1-c1cnc2[nH]nc(-c3nc4c(-c5cc(F)cc(CNS(C)(=O)=O)c5)nccc4[nH]3)c2c1
InChIKey: GFVYCQCDDPCRJJ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 528.57, ALogP 4.12, HBA 7, HBD 3, PSA 142.2, QED 0.3
Compound (SMILES): O=C(O)C(=O)Nc1ccc2nc(NC(=O)c3cc(Br)c(Br)[nH]3)[nH]c2c1
InChIKey: IQFVZJHGVZQCBU-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase using relaxed pNO1 plasmid DNA as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 471.07, ALogP 2.69, HBA 4, HBD 5, PSA 139.97, QED 0.37