lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): FC(F)c1cncc(-c2ccc3ncc4nnc(C5=CCCCC5)n4c3c2)c1
InChIKey: LQCFRUUPBAMHIY-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of full-length N-terminal FLAG-tagged human ATM expressed in HEK293-6E cells using biotin-PEG2-SVEPPLSQETFSD as substrate preincubated for 15 mins followed by substrate addition and measured after 90 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 5420 nM (pChEMBL 5.269999980926514)
Descriptors: MW 377.4, ALogP 5.23, HBA 5, HBD 0, PSA 55.97, QED 0.49
Compound (SMILES): Cc1cc(COc2ccc(C(F)(F)F)cc2Cl)cc(C(=O)O)c1
InChIKey: UEZJRCWWSLRIID-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 100 uM of conjugated bilirubin by HTRF assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 344.72, ALogP 4.94, HBA 2, HBD 1, PSA 46.53, QED 0.85
Compound (SMILES): CC(=O)N1Cc2cc(S(C)(=O)=O)ccc2C1C(=O)Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: QYYZXEPEVBXNNA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 524.44, ALogP 3.44, HBA 5, HBD 2, PSA 103.78, QED 0.6
Compound (SMILES): CN1CC=C(C2=Nc3cc(F)ccc3Nc3ccc(Cl)cc32)CC1
InChIKey: ROGOJMMVYYXWMQ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2 receptor expressed in CHO cells assessed as inhibition of dopamine-induced calcium accumulation
Measurement: Ki = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 341.82, ALogP 4.92, HBA 3, HBD 1, PSA 27.63, QED 0.8
Compound (SMILES): N[C@@H](Cn1nnc(-c2ccc(Oc3ccc(Cl)cc3)cc2)n1)C(=O)O
InChIKey: PVRNNKZLXJIKKA-AWEZNQCLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG stably expressed in HEK293 cell membranes measured after 90 mins by microbeta liquid scintillation counting method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 359.77, ALogP 2.2, HBA 7, HBD 2, PSA 116.15, QED 0.69
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N/N=C\c2ccccc2)cc1
InChIKey: UCTQYHNHFBXNSN-YBEGLDIGSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 by stopped-flow CO2 hydration assay
Measurement: Ki = 1974 nM (pChEMBL 5.710000038146973)
Descriptors: MW 303.34, ALogP 1.1, HBA 4, HBD 2, PSA 101.62, QED 0.65
Compound (SMILES): O=C(O)c1cc2cc(-c3ccccc3F)c(O)cc2oc1=O
InChIKey: AURLBLPCECMPLX-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as reduction in dynamic mass redistribution response in presence of GPR35 antagonist ML-145 by DMR assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 300.24, ALogP 3, HBA 4, HBD 2, PSA 87.74, QED 0.71
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: VAOXNKVUDSXJMW-CVGILMMLSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 806.97, ALogP 3.88, HBA 6, HBD 8, PSA 221.39, QED 0.04
Compound (SMILES): O=C(O)[C@H](O)CC[C@H]1CN(S(=O)(=O)c2cccc(C(F)(F)F)c2)c2cc(-c3cc(F)ccc3F)ccc2O1
InChIKey: QBXHWIJRVQBXEF-HTAPYJJXSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at human PXR-gamma expressed in HEK293 cells assessed as transcriptional activity in presence of ursolic acid by Gal4-luciferase reporter assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 557.49, ALogP 4.83, HBA 5, HBD 2, PSA 104.14, QED 0.4
Compound (SMILES): CNS(=O)(=O)c1ccc2c(c1)CN(C(=O)C1CCO1)C2C(=O)Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: UMGNIRMNYZUZHY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 581.49, ALogP 2.72, HBA 6, HBD 3, PSA 125.04, QED 0.45
Compound (SMILES): COc1cccc(CCn2c3c(c4c(O)cccc42)C(=O)c2ccccc2-3)c1
InChIKey: YCDWMFFYKRLDQW-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Non-competitive inhibition of human ABCG2 transfected in human HEK293 cells assessed as Ki2 for inhibition of mitoxantrone efflux measured after 30 mins by FACS Calibur cytometric analysis
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 369.42, ALogP 4.81, HBA 4, HBD 1, PSA 51.46, QED 0.49
Compound (SMILES): CCS(=O)(=O)c1ccc2c(c1)CN(C(C)=O)[C@@H]2C(=O)Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: WUZNZQZEJJUMBN-SFHVURJKSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 538.47, ALogP 3.83, HBA 5, HBD 2, PSA 103.78, QED 0.56
Compound (SMILES): Cc1cc(C(=O)O)ccc1-c1ccc(Cl)c(-c2ccc(C(F)(F)F)cc2CN2C(=O)O[C@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2C)c1
InChIKey: QTXRBYGCEKYZNF-ADKRDUOOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 716, ALogP 10.82, HBA 3, HBD 1, PSA 66.84, QED 0.2
Compound (SMILES): O=[N+]([O-])C1=Cc2cc(I)ccc2OC1C(F)(F)F
InChIKey: OPOOLSURVZPHRO-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Inhibition of dopamine D5 receptor (unknown origin)
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 371.05, ALogP 3.23, HBA 3, HBD 0, PSA 52.37, QED 0.43
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OC/C=C/COc3cccc2c3)cc1OC
InChIKey: QGOZUOJTJYDDMS-YBMMQTEXSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12 (unknown origin) expressed in Escherichia coli BL21 (DE2) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 768 nM (pChEMBL 6.119999885559082)
Descriptors: MW 727.9, ALogP 8.01, HBA 9, HBD 0, PSA 101.99, QED 0.17
Compound (SMILES): CC(C)CCc1cccc(C(=O)Nc2c(O)c3ccc(NS(=O)(=O)c4ccccc4)cc3oc2=O)c1
InChIKey: ZFOLEABRHPFKAG-UHFFFAOYSA-N
Target: Microtubule-associated protein 1 light chain 3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ8
Assay: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3B by time-resolved FRET assay
Measurement: Ki = 13800 nM (pChEMBL 4.860000133514404)
Descriptors: MW 506.58, ALogP 5.14, HBA 6, HBD 3, PSA 125.71, QED 0.28
Compound (SMILES): COC[C@H](C)n1c(C2CCOCC2)nc2cnc3cc(-c4c(C)noc4C)c(OC)cc3c21
InChIKey: HYPXHDJBILNWLI-AWEZNQCLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from recombinant human N-terminal 6His-tagged BRD4-BD1 Y390A mutant (1 to 477 residue) expressed in Escherichia coli incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 450.54, ALogP 4.97, HBA 8, HBD 0, PSA 84.43, QED 0.41
Compound (SMILES): CC(=O)Nc1cc(C(=O)Nc2cncc(OCC3CCN(Cc4ccc(F)cc4)CC3)c2)ccn1
InChIKey: IGURROANDGIDJI-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant N-terminal His-tagged GSK3beta expressed in Escherichia coli using RRRPASVPPSPSLS RHS(pS)HQRR as substrate incubated for 30 mins in presence of ATP by Kinase-Glo reagent based luminescence assay
Measurement: IC50 = 3508 nM (pChEMBL 5.460000038146973)
Descriptors: MW 477.54, ALogP 4.12, HBA 6, HBD 2, PSA 96.45, QED 0.51
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cc(c(F)cc1F)C(=O)NCc1cncc(c1)-c1ccnc3ccc-2nc13
InChIKey: XEVSZKHCEQKQQL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) using Luciferin-ME as substrate at 10 uM preincubated with enzyme and substrate for 5 mins followed by addition of NADPH regeneration system and measured after 60 mins by luminescence method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 560.54, ALogP 4.08, HBA 8, HBD 2, PSA 136.06, QED 0.31
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(Nc4cccc(C(F)(F)F)c4)n3)cn2)CC1
InChIKey: YNGWEWBJFQRFCH-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 96.1 nM (pChEMBL 7.019999980926514)
Descriptors: MW 463.9, ALogP 4.78, HBA 7, HBD 2, PSA 69.21, QED 0.56
Compound (SMILES): Cn1c(Cc2nn(CCCO)c(=O)c3ccccc23)nnc1SCC(=O)Nc1ccc(Cl)cc1Cl
InChIKey: HDAVYAJNOJTKBR-UHFFFAOYSA-N
Target: Interleukin-15 (SINGLE PROTEIN), Homo sapiens
UniProt: P40933
Assay: Inhibition of IL-15-induced STAT3 phosphorylation in human NK92 cells incubated for 30 mins followed by IL-15 stimulation and measured after 1 hr by alphascreen assay
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 533.44, ALogP 3.54, HBA 9, HBD 2, PSA 114.93, QED 0.32
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3cccnn3)ncc2Cl)c1
InChIKey: XBUASUBEROZIQU-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 2064 nM (pChEMBL 5.679999828338623)
Descriptors: MW 366.73, ALogP 4.43, HBA 6, HBD 2, PSA 75.62, QED 0.71
Compound (SMILES): CC(C)CC(=O)N1CC(C(N)=O)Oc2ccccc21
InChIKey: XDCZQBOBAHSWEH-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of His6-tagged/TEV fused SIRT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 262.31, ALogP 1.31, HBA 3, HBD 1, PSA 72.63, QED 0.89
Compound (SMILES): COc1ccc2ncc(F)c(C[C@H](O)[C@H]3OC[C@H](NCc4cc5c(cn4)SCC(=O)N5)CO3)c2n1
InChIKey: ASSSIFUQVIZHMH-LBDOCTSOSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA Gyrase D83N mutant assessed as reduction in supercoiling pBR322 DNA by measuring relaxation by bromophenol blue staining based TAE gel method
Measurement: IC50 = 63000 nM (pChEMBL 4.199999809265137)
Descriptors: MW 501.54, ALogP 1.65, HBA 10, HBD 3, PSA 127.72, QED 0.44
Compound (SMILES): CCc1cc(Nc2nc(N[C@@H](C)c3ccc(F)cn3)nc3cccc(C)c23)n[nH]1
InChIKey: AZCHQQLGTDJHFL-ZDUSSCGKSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of recombinant human IGF-1R (959 to end residues) using KKKSPGEYVNIEF as substrate incubated for 40 mins in presence of [gamma-33ATP] by radiometric scintillation counting method
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 391.45, ALogP 4.67, HBA 6, HBD 3, PSA 91.41, QED 0.44
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NCc6ccc(F)cc6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: DOXKACRKTSDDLU-BNZUBNTLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 580.74, ALogP 6.84, HBA 5, HBD 1, PSA 42.96, QED 0.32
Compound (SMILES): COc1ccc(CSS(=O)(=O)c2ccc(C)cc2)cc1
InChIKey: SJBOKLOBSYZREV-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured by Ellman's method
Measurement: IC50 = 201.5 nM (pChEMBL 6.699999809265137)
Descriptors: MW 308.42, ALogP 3.63, HBA 4, HBD 0, PSA 43.37, QED 0.79
Compound (SMILES): O=C(CCCCCONC(=O)c1cnc2ccccc2n1)NO
InChIKey: LUTFGXARJQOWLQ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC6 (1 to 1215 residues) expressed in baculovirus infected insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 90 mins by fluorimetry
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 318.33, ALogP 1.36, HBA 6, HBD 3, PSA 113.44, QED 0.38
Compound (SMILES): Fc1ccc2c(-c3ccc4nnn(CCN5CCNCC5)c4c3)c[nH]c2c1
InChIKey: NWBMXBXPSXUWBK-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of full length N-terminal/C-terminal his-tagged human TDO expressed in Escherichia coli BL21 (DE3) assessed as N-formylkynurenine formation using L-tryptophan as substrate by UV2100 spectrophotometer analysis
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 364.43, ALogP 2.62, HBA 5, HBD 2, PSA 61.77, QED 0.58
Compound (SMILES): Cc1c(C(=O)O)cnc2c(NC(=O)NCCc3ccc(S(N)(=O)=O)cc3)cnn12
InChIKey: NMDVARAMHFVDHU-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 by stopped-flow CO2 hydration assay
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 418.44, ALogP 0.75, HBA 7, HBD 4, PSA 168.78, QED 0.46
Compound (SMILES): CSc1nccc(-c2c(-c3ccc(F)cc3)nc3c(N(C)C)nccn23)n1
InChIKey: PLILNLDCVRFBMR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of human recombinant CDK5/ p25 expressed in bacterial expression system using histone H1 as substrate in presence of [gamma-33P]ATP by radiometric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.45, ALogP 3.78, HBA 7, HBD 0, PSA 59.21, QED 0.4
Compound (SMILES): Cc1ccc(N(CC(F)(F)F)S(=O)(=O)C2CC3OC2C(c2ccc(NC(=O)CCCCCCC(=O)O)cc2)=C3c2ccc(O)cc2)cc1
InChIKey: DIHJQOKOOZCBRS-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at ERbeta (unknown origin) expressed in human HEK293T cells assessed as transcriptional activities by measuring ERE driven reporter gene expression measured after 24 hrs by dual luciferase reporter gene assay
Measurement: EC50 = 1301 nM (pChEMBL 5.889999866485596)
Descriptors: MW 686.75, ALogP 6.91, HBA 6, HBD 3, PSA 133.24, QED 0.16
Compound (SMILES): CCOC(=O)[C@@H](Cc1cn(C)c2ccccc12)NC(=O)[C@@H](N)CC(C)C.Cl
InChIKey: PXFDVONNVFXYEP-MCJVGQIASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human hepatocytes
Measurement: IC50 = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 359.47, ALogP 2.14, HBA 5, HBD 2, PSA 86.35, QED 0.71
Compound (SMILES): Cc1c2nc(C(=O)O)cc(Cl)c2cc2c(Cl)cc(C(=O)O)nc12
InChIKey: LLXHLQZJSVCSRH-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as reduction in dynamic mass redistribution response in presence of GPR35 antagonist ML-145 by DMR assay
Measurement: IC50 = 2529 nM (pChEMBL 5.599999904632568)
Descriptors: MW 351.15, ALogP 3.79, HBA 4, HBD 2, PSA 100.38, QED 0.68
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(c1ccccc1)c1ccccc1
InChIKey: BLWGMVWWARNRMV-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-P129 from human histamine H3 receptor expressed in sf9 insect cell membranes co-expressing Galphai2/Gbeta1gamma2 incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 9120.11 nM (pChEMBL 5.039999961853027)
Descriptors: MW 422.56, ALogP 3.37, HBA 4, HBD 4, PSA 118.42, QED 0.26
Compound (SMILES): CC(C)(C)c1ccc(-c2ccc3c(C(=O)NCC4CCNCC4)c[nH]c3c2)cc1
InChIKey: QNMZAUPLZFCYGX-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B (49 to 96 residues)/NS3 (2 to 184 residues) protease expressed in Escherichia coli BL21 using Bz-Nle-Lys-Lys-Arg-AMC as substrate preincubated for 10 mins by fluorescence-based biochemical assay
Measurement: IC50 = 35100 nM (pChEMBL 4.460000038146973)
Descriptors: MW 389.54, ALogP 4.86, HBA 2, HBD 3, PSA 56.92, QED 0.6
Compound (SMILES): NC(=O)C1CN(Cc2cccc([N+](=O)[O-])c2)c2ccccc2O1
InChIKey: DICXQDJAQVPOML-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of His6-tagged/TEV fused SIRT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 313.31, ALogP 1.85, HBA 5, HBD 1, PSA 98.7, QED 0.69
Compound (SMILES): COc1ccccc1-c1n[nH]cc1N1CCNCC1
InChIKey: ZHHFTZVFFWFQPP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Antagonist activity at human 5-HT7 receptor expressed in HEK293 cells assessed as reduction in cAMP accumulation incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 4061 nM (pChEMBL 5.389999866485596)
Descriptors: MW 258.32, ALogP 1.49, HBA 4, HBD 2, PSA 53.18, QED 0.88
Compound (SMILES): COc1cccc(C2CC(c3cc(F)ccc3F)=NN2c2ccc(S(N)(=O)=O)cc2)c1OC
InChIKey: NDXDTKKYWMJWOB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2
Measurement: IC50 = 4.45 nM (pChEMBL 8.350000381469727)
Descriptors: MW 473.5, ALogP 3.99, HBA 6, HBD 1, PSA 94.22, QED 0.58
Compound (SMILES): CCOCc1[nH]c(=O)c(-c2nnc(Cc3ccc(Cl)nc3)o2)c(O)c1-c1c(OC)cccc1OC
InChIKey: CYACKGRXWPIXDR-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Intracellular cAMP Accumulation Assay: HEK293 cells stably expressing human APJ receptor were used to assess the activity of compounds. Cultured cells were detached and resuspended in the cAMP Homogeneous Time-Resolved Fluorescence (HTRF) assay buffer (Cisbio cat; #62AM4PEJ). The assay was performed in 384-well assay plates (Perkin-Elmer; cat #6008289) according to assay protocol provided by the manufacturer. Serial dilutions of a compound together with assay buffer containing 0.2 nM IBMX and 2 μM forskolin were added to each well containing 5,000 cells and incubated for 30 minutes at room temperature. Subsequently, cAMP D2 reagent was added in the lysis buffer followed by the EuK antibody (Cisbio; cat #62AM4PEJ) and incubated for 60 min. The fluorescence emission ratio was measured using fluorometer. The intracellular cAMP concentrations (compound-stimulated inhibition of forskolin-mediated cAMP production) were calculated by extrapolation from a standard curve using known cAMP concentrations. The EC50 values were obtained by fitting the data to a sigmoidal concentration-response curve with variable slope. The maximal achievable inhibition of forskolin-induced cAMP levels (Ymax) for each compound was expressed as relative percentage of inhibition attained using pyroglutamated apelin-13 ((Pyr1)apelin-13) peptide, which was set to 100%.The examples disclosed below were tested in the APJ in vitro assays described above and were found having human APJ cyclic AMP (hcAMP) activity. The EC50 value of each compound is presented at the end of the example description.
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 498.92, ALogP 3.99, HBA 9, HBD 2, PSA 132.59, QED 0.33
Compound (SMILES): CCC(Sc1nc2c(cnn2C)c(=O)n1-c1ccccc1)c1ccccc1
InChIKey: UJZUXSRRZFTERS-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of human ALDH1A3 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 376.49, ALogP 4.36, HBA 6, HBD 0, PSA 52.71, QED 0.38
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(C(=O)N/N=C\c3ccc(Cl)cc3)cc2-c2cccs2)cc1
InChIKey: UHJIFJNRYFABBN-CFRMEGHHSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 485.98, ALogP 3.67, HBA 7, HBD 2, PSA 119.44, QED 0.32
Compound (SMILES): NS(=O)(=O)c1cc2cc(Cl)cc(Cl)c2oc1=O
InChIKey: ULIGWIVYSYNUDP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 518.2 nM (pChEMBL 6.289999961853027)
Descriptors: MW 294.11, ALogP 1.75, HBA 4, HBD 1, PSA 90.37, QED 0.81
Compound (SMILES): NC(=O)C1CN(Cc2cccc(Br)c2)c2ccccc2O1
InChIKey: GYPMBPGUPMFWIY-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of His6-tagged/TEV fused SIRT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 347.21, ALogP 2.7, HBA 3, HBD 1, PSA 55.56, QED 0.93
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@H](Cc1cccc2ccccc12)C(=O)N1Cc2[nH]c3ccccc3c2C[C@@H]1C(=O)O
InChIKey: QMMRLPSWPSDJFS-FKFMCLSGSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing PDZ-Rho-Gef-RLucll and rGFP-CAAX assessed as induction of recruitment of Galpha12 to cell membrane using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1666.96
Compound (SMILES): c1ccc(-c2ccc3c(Nc4ccc5scnc5c4)ccnc3c2)cc1
InChIKey: XNKMNBXGVDBVPN-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin)
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 353.45, ALogP 6.26, HBA 4, HBD 1, PSA 37.81, QED 0.42
Compound (SMILES): CCOc1cccc2cc(S(N)(=O)=O)c(=O)oc12
InChIKey: LXRSALAUTHMGJG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 51.5 nM (pChEMBL 7.289999961853027)
Descriptors: MW 269.28, ALogP 0.84, HBA 5, HBD 1, PSA 99.6, QED 0.83
Compound (SMILES): O=c1c2cc(NCc3ccc(Cl)cc3O)ccc2nc2n1CCC2
InChIKey: TVQYUDLGIGPQTI-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of human amyloid beta (1 to 42) self-induced aggregation measured after 48 hrs by ThT flourescence assay
Measurement: IC50 = 7020 nM (pChEMBL 5.150000095367432)
Descriptors: MW 341.8, ALogP 3.31, HBA 5, HBD 2, PSA 67.15, QED 0.77
Compound (SMILES): O=c1c2c(Cl)cccc2nc([C@@H](Nc2ncnc3nc[nH]c23)C2CCC2)n1-c1ccccc1
InChIKey: UDSRXNFTFHNQAG-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human full length His-tagged p110gamma expressed in baculovirus expression system measured after 60 mins in presence of ATP by ATP-competitive binding assay
Measurement: IC50 = 63.8 nM (pChEMBL 7.199999809265137)
Descriptors: MW 457.93, ALogP 4.66, HBA 7, HBD 2, PSA 101.38, QED 0.4
Compound (SMILES): Cc1cccc(-c2n[nH]cc2N2CCCNCC2)c1
InChIKey: DZSVIKVOAPBNLM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Antagonist activity at human 5-HT7 receptor expressed in HEK293 cells assessed as reduction in cAMP accumulation incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 1053 nM (pChEMBL 5.980000019073486)
Descriptors: MW 256.35, ALogP 2.18, HBA 3, HBD 2, PSA 43.95, QED 0.87
Compound (SMILES): Cn1c(Cl)cnc1CNc1ccc2sncc2c1
InChIKey: CSSDJSDSVXAGMG-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Agonist activity at human TRPV1 expressed in CHO cells assessed as increase in capsaicin-induced intracellular calcium level measured after 1 hr by FLIPR assay
Measurement: EC50 > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 278.77, ALogP 3.3, HBA 5, HBD 1, PSA 42.74, QED 0.8
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc(C(=O)c2ccc(F)cc2)cs1)C1CCN(C(=O)c2cnc(N3CCN(CCCOc4cc5ncnc(Nc6n[nH]c(C)c6C)c5cc4S(=O)(=O)C(C)(C)C)CC3)cn2)CC1
InChIKey: VXCZVPTVGMPYKY-RTBFYXABSA-N
Target: Baculoviral IAP repeat-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13489
Assay: Binding affinity to human 6His-thr cIAP1 BIR3 (253 to 363) domain expressed in Escherichia coli measured after 105 mins in dark by time-resolved fluorescence laser-equipped multimode plate reader
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 1107.35
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3cncnc3)ncc2Cl)c1
InChIKey: FHUDSNATRGHUNK-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 366.73, ALogP 4.43, HBA 6, HBD 2, PSA 75.62, QED 0.71
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NCc6ccc(OCC7CCC7)cc6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: JQOIORAHDPZIRN-ULPHGGBCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 224.5 nM (pChEMBL 6.650000095367432)
Descriptors: MW 646.87, ALogP 7.88, HBA 6, HBD 1, PSA 52.19, QED 0.23
Compound (SMILES): O=C(NCc1ccccc1CN1CCc2cc(O)c(O)cc2C1)c1cccc(Br)c1
InChIKey: PTUSEMHIKWRSIP-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylspiperone from dopamine D3 receptor (unknown origin)
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 467.36, ALogP 4.35, HBA 4, HBD 3, PSA 72.8, QED 0.49
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(C)c1ccc(Br)cc1
InChIKey: SJEJWKDCZAYCBI-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-P129 from human histamine H3 receptor expressed in sf9 insect cell membranes co-expressing Galphai2/Gbeta1gamma2 incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 12882.5 nM (pChEMBL 4.889999866485596)
Descriptors: MW 439.38, ALogP 3.1, HBA 4, HBD 4, PSA 118.42, QED 0.31
Compound (SMILES): C=CCOCC(O)C[Se]CC(O)CSc1ccc(S(N)(=O)=O)cc1
InChIKey: RHZDWPRIFIBLMT-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 390.4 nM (pChEMBL 6.409999847412109)
Descriptors: MW 440.45
Compound (SMILES): CC(C)c1cccc(CNC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)CC(c2ccccc2)c2ccccc2)c1
InChIKey: FSNRTXIQLFBFDM-SZAHLOSFSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 expressed in baculovirus expression system using Rh-EVNLDAEFK-quencher as substrate incubated for 60 mins by FRET assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 520.72, ALogP 6.21, HBA 3, HBD 3, PSA 61.36, QED 0.2
Compound (SMILES): COc1ncc(C2=CCOCC2)cc1S(=O)(=O)Nc1ccnc(C)c1
InChIKey: MQQOMKBMLHBDFG-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal His6-tagged full length P110beta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 361.42, ALogP 2.4, HBA 6, HBD 1, PSA 90.41, QED 0.88
Compound (SMILES): O=C1c2cc(Cl)ccc2CC1CCN1CCN(c2ccccn2)CC1
InChIKey: BODKZKXTTLFUIE-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human dopamine D3 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 407 nM (pChEMBL 6.389999866485596)
Descriptors: MW 355.87, ALogP 3.3, HBA 4, HBD 0, PSA 36.44, QED 0.84
Compound (SMILES): CCC[C@H](Nc1ncnc2nc[nH]c12)c1nc2cccc(Cl)c2c(=O)n1-c1ccccc1
InChIKey: QKDLMWZHWDLIHJ-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human full length His-tagged p110gamma expressed in baculovirus expression system measured after 60 mins in presence of ATP by ATP-competitive binding assay
Measurement: IC50 = 18.3 nM (pChEMBL 7.739999771118164)
Descriptors: MW 445.91, ALogP 4.66, HBA 7, HBD 2, PSA 101.38, QED 0.39
Compound (SMILES): CCn1nc(C)cc1C(=O)/N=c1\[nH]c2cc(-c3ncn[nH]3)cc(OC)c2n1C/C=C/Cn1/c(=N/C(=O)c2cc(C)nn2CC)[nH]c2cc(C(N)=O)cc(OCCCN3CCOCC3)c21
InChIKey: RZBQZKAZIZWIRZ-CMDGGOBGSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Binding affinity to 6His-tagged human STING measured after 3 hrs by HTRF assay
Measurement: EC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 873.98, ALogP 3.03, HBA 15, HBD 4, PSA 251.53, QED 0.08
Compound (SMILES): Cc1ccc(S(=O)(=O)NCC(C)(C)O)cc1-c1cnc(N)c(-c2cnn(C)c2C)c1
InChIKey: HCUAPUXZDWBUPG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Kinase Glo Luminescent Kinase Assay (Kglo) for PI 3-Kinase Alpha (A), PI 3-Kinase Beta (B), Vps34 (C), PI 4-Kinase Beta (D): The luminescence-based ATP detection reagent KinaseGlo was obtained from Promega, (Cat. No. V6714, Lot No. 236161) through Catalys, Wallisellen, Switzerland. L-alpha-phosphatidylinositol (PI, liver, bovine) was obtained from Avanti Polar Lipid (Cat. No. 840042C, Lot#LPI-274), phosphatidylinositol-4,5-bisphosphate (PIP(4,5)2) was obtained from Avanti Polar Lipid (Cat. No. 840046X). L-α-phosphatidylserine (PS) was obtained from Avanti Polar Lipid (Cat. No. 840032C), n-octylglucoside from Avanti Polar Lipid (Cat. No. 10634425001). Luminescence is a well established readout to determine ATP concentrations and can thus be used to follow the activity of many kinases regardless of their substrate. The Kinase Glo Luminescent Kinase Assay (Promega, Madison, Wis., USA) is a homogeneous HTS method of measuring kinase activity by quantifying the amount of ATP remaining in solution following a kinase reaction.50 nL of compound dilutions were dispensed onto black 384-well low volume Non Binding Styrene (NBS) plates (Costar Cat. No. NBS#3676). L-α-phosphatidylinositol (PI), provided as 10 mg/ml solution in methanol, was transferred into a glass tube and dried under a nitrogen beam. It was then resuspended in 3% OctylGlucoside (1-O-n-octyl-beta-D-glucopyranoside) by vortexing and stored at 4° C. 5 μl of a mix of PI/OctylGlucoside with the PI 3-kinase alpha and PI 3-kinase beta subtypes, or Vps34 or PI 4-kinase beta were added. Kinase reactions were started by the addition of 5 μl of an ATP-mix containing in a final volume 10 μl 10 mM TRIS-HCl pH 7.5, 3 mM MgCl2, 50 mM NaCl, 0.05% CHAPS, 1 mM DTT and 1 μM ATP at room temperature. Reactions were stopped with 10 μl of KinaseGlo and plates were read 10 mins later in a Synergy2 reader using an integration time of 0.1 seconds per well. 2.5 μM of NVP-BGT226 (1-(3-(trifluoromethyl)-4-(piperazin-1-yl)phenyl)-8-(6-methoxypyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-one) was added to the assay plates to generate the 100% inhibition of the kinase reaction, and the 0% inhibition was given by the solvent vehicle (90% DMSO in water). (1-(3-(trifluoromethyl)-4-(piperazin-1-yl)phenyl)-8-(6-methoxypyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-one) was used as a reference compound and included in all assay plates in the form of 16 dilution points in duplicate.IC50 values of the percentage inhibition of each compound at 8 concentrations (10, 3.0, 1.0, 0.3, 0.1, 0.030, 0.010 and 0.003 μM) n=2 were derived by fitting a sigmoidal dose-response curve to a plot of assay readout over inhibitor concentration as described. All fits were performed with the program XLfit4 (ID Business Solutions, Guildford, UK).
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 429.55, ALogP 2.4, HBA 7, HBD 3, PSA 123.13, QED 0.55
Compound (SMILES): O=C(c1nccs1)N1CC[C@@H](Nc2nccc(-n3cc(C4CC4)nc3-c3ccccc3)n2)C1
InChIKey: WMOACOPVFVMARL-GOSISDBHSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 using 3-[2-(N,N-diethylamino)ethyl]-7-methoxy-4-methyl coumarin as a substrate incubated for 45 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 457.56, ALogP 3.99, HBA 8, HBD 1, PSA 88.83, QED 0.47
Compound (SMILES): C[C@@H]1OC[C@@](O)(NC(=O)c2ccc(S(N)(=O)=O)cc2)[C@H](O)[C@H]1O
InChIKey: OBUUTXDXOMKCJI-CXSMTQNASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow assay
Measurement: IC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 346.36, ALogP -2.11, HBA 7, HBD 5, PSA 159.18, QED 0.39
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@H](Cc1cccc2ccccc12)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: XNRQRGITNMKWKU-XRYFJGBWSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing PDZ-Rho-Gef-RLucll and rGFP-CAAX assessed as induction of recruitment of Galpha12 to cell membrane using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 1615.91
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CNc2nc3ccc(OC(F)(F)F)cc3s2)cc1
InChIKey: AWYGNLMJWIHGLU-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human CA7 pre-incubated for 15 mins measured by stopped flow CO2 hydration assay
Measurement: Ki = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 460.46, ALogP 2.57, HBA 7, HBD 3, PSA 123.41, QED 0.5
Compound (SMILES): Cc1ccc2nc3c(c(N)c2c1)CCCC3.Cl
InChIKey: YZRIGVPNZAZYBZ-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2A (PROTEIN COMPLEX), Homo sapiens
UniProt: Q12879
Assay: Inhibition of human GluN1a/GluN2A receptor expressed in HEK293 cells assessed as inhibition of glycine/glutamate-induced current measured at -60 mV holding potential by whole-cell patch clamp method
Measurement: IC50 = 12280 nM (pChEMBL 4.909999847412109)
Descriptors: MW 212.3, ALogP 3, HBA 2, HBD 1, PSA 38.91, QED 0.73
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](CCCCN)C(N)=O
InChIKey: NHNGIHXOKMSFOD-QNXSJEMLSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 778.95, ALogP 4.75, HBA 6, HBD 6, PSA 185.51, QED 0.07
Compound (SMILES): COCCNC(=O)c1cc(-n2ncc3cc(Nc4ccccc4Cl)c(F)cc32)cs1
InChIKey: XTFFMIPOKWLBRH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38 alpha (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 444.92, ALogP 5, HBA 6, HBD 2, PSA 68.18, QED 0.39
Compound (SMILES): CCn1cnc(NC(=O)c2cc3c(nc2OC)nc(C(O)(c2ccccc2F)c2ccccc2F)n3CC)n1
InChIKey: ILOZSKZWTJTARE-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into histones by microbeta scintillation counting analysis
Measurement: IC50 = 0.01 nM (pChEMBL 11)
Descriptors: MW 533.54, ALogP 3.89, HBA 9, HBD 2, PSA 119.98, QED 0.31
Compound (SMILES): O=C(O)c1ccc(-c2ccncn2)cc1C1CCCC1
InChIKey: AGBHEXCDTREOQR-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N5S9
Assay: Inhibition of human CAMKK1 using CAMKKtide as substrate assessed as residual activity by [gamma-33P]-ATP assay relative to control
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 268.32, ALogP 3.5, HBA 3, HBD 1, PSA 63.08, QED 0.92
Compound (SMILES): O=C(CCCCCONC(=O)c1ccc2ccccc2c1)NO
InChIKey: YDGNQLWJPVIXKO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC6 (1 to 1215 residues) expressed in baculovirus infected insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 90 mins by fluorimetry
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 316.36, ALogP 2.57, HBA 4, HBD 3, PSA 87.66, QED 0.4
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(OC)c(c3)OCCCC(=O)COc3cccc2c3)cc1OC
InChIKey: DOJMFMVTYZITGI-KLBQNTFLSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12 (unknown origin) expressed in Escherichia coli BL21 (DE2) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 757.92, ALogP 7.8, HBA 10, HBD 0, PSA 119.06, QED 0.21
Compound (SMILES): CN(C)CCCOc1ccc(-c2ccc3ncc4nnc(C5CCOCC5)n4c3c2)cn1
InChIKey: OLUUKHAHFFWDFW-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of full-length N-terminal FLAG-tagged human ATM expressed in HEK293-6E cells using biotin-PEG2-SVEPPLSQETFSD as substrate preincubated for 15 mins followed by substrate addition and measured after 90 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 432.53, ALogP 3.56, HBA 8, HBD 0, PSA 77.67, QED 0.41
Compound (SMILES): NC(=O)c1cccc2c(N[C@H](CN3CCC3)c3cccc(C(F)(F)F)c3)ncnc12
InChIKey: YFBSBJBNKSZCLY-QGZVFWFLSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQS7
Assay: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 415.42, ALogP 3.61, HBA 5, HBD 2, PSA 84.14, QED 0.64
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NCCN1CCN(CCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ORHNRASLJVKVAU-WBVZDLBWSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from human muscarinic M3 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 173.78 nM (pChEMBL 6.760000228881836)
Descriptors: MW 831.08, ALogP 1.52, HBA 11, HBD 8, PSA 234.35, QED 0.05
Compound (SMILES): CC(C)(C)OC(=O)Nc1ccc(-c2cc(NC(=O)CCCCCCC(=O)NO)no2)cc1
InChIKey: HACPSCZAVPAEID-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 0.42 nM (pChEMBL 9.380000114440918)
Descriptors: MW 446.5, ALogP 4.47, HBA 7, HBD 4, PSA 142.79, QED 0.24
Compound (SMILES): Cc1c(C2(c3ccc(C(F)(F)F)c(C#N)c3)CC2)c[nH]c1C(=O)NC(C)c1nc[nH]n1
InChIKey: QOYSJYDAYLKBNM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by QPatch assay
Measurement: IC50 = 20400 nM (pChEMBL 4.690000057220459)
Descriptors: MW 428.42, ALogP 3.9, HBA 4, HBD 3, PSA 110.25, QED 0.57
Compound (SMILES): Nc1nc(Cl)cc(N(Cc2cccs2)C2CC2)n1
InChIKey: PDWZXKSZLRVSEH-UHFFFAOYSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: ELISA-based Correlate-EIA Direct cAMP Assay: INS-1E insulinoma cells were incubated in 2.5 mM glucose Krebs-Ringer buffer (pH 7.5) supplemented with 2 mM sodium bicarbonate, 10 mM HEPES, and 0.1% BSA for 2 h before start of the experiment. At time zero for each experiment, media was switched to Krebs-Ringer buffer containing 2.5 mM glucose or 16 mM glucose in the presence of 500 μM IBMX and inhibitor at the shown concentrations. After 10 min cells were lysed in 200 μl 0.1 M HCl. Intracellular cAMP contents were determined using Correlate-EIA Direct Assay (Assay Designs, Inc).
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 280.78, ALogP 2.94, HBA 5, HBD 1, PSA 55.04, QED 0.88
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(C(=O)N/N=C\c3ccc(O)cc3)cc2-c2cccs2)cc1
InChIKey: ZAMBBTLODSRFIK-QRVIBDJDSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 467.53, ALogP 2.72, HBA 8, HBD 3, PSA 139.67, QED 0.3
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@H](Cc1cccc2ccccc12)C(=O)N1Cc2ccccc2C[C@H]1C(=O)O
InChIKey: UULVZEKDGLNMRS-GENUFQOQSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing PDZ-Rho-Gef-RLucll and rGFP-CAAX assessed as induction of recruitment of Galpha12 to cell membrane using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 1627.92
Compound (SMILES): Cc1n[nH]c2ccc(-c3cc(N[C@@H](CO)c4ccccc4)cnc3Cl)cc12
InChIKey: SHDGEOLPEYTGCG-FQEVSTJZSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 378.86, ALogP 4.73, HBA 4, HBD 3, PSA 73.83, QED 0.44
Compound (SMILES): Cc1cc(/C=C2\Oc3cc(OCC(C)C)ccc3C2=O)cc(C)c1OCC(=O)O
InChIKey: DMYMKTPYFGFERF-UKWGHVSLSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human PPARdelta transfected in human HEK293 cells incubated for 18 hrs by Renilla/Firefly dual-luciferase reporter assay
Measurement: EC50 = 2679 nM (pChEMBL 5.570000171661377)
Descriptors: MW 396.44, ALogP 4.42, HBA 5, HBD 1, PSA 82.06, QED 0.7
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NCc6ccc(N)cc6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: JLPJPSBLYDTCBY-BNZUBNTLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 577.77, ALogP 6.28, HBA 6, HBD 2, PSA 68.98, QED 0.31
Compound (SMILES): COc1ccccc1N1CCN(Cc2ccc(CN3C(=O)c4ccccc4S3(=O)=O)cc2)CC1
InChIKey: SZOQFKJMAIDYBY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6R expressed in human HEK293 cells
Measurement: Ki = 10090 nM (pChEMBL 5)
Descriptors: MW 477.59, ALogP 3.36, HBA 6, HBD 0, PSA 70.16, QED 0.54
Compound (SMILES): COc1cc2c(cc1O)CN(Cc1ccccc1CNC(=O)c1ccc(C#N)cc1)CC2
InChIKey: IGMYCJFCNUVBNZ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-methylspiperone from dopamine D4 receptor (unknown origin)
Measurement: Ki = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 427.5, ALogP 3.76, HBA 5, HBD 2, PSA 85.59, QED 0.63
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CNc2ccccc2F)cc1
InChIKey: NHHQCGLSMQEPHC-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human CA7 pre-incubated for 15 mins measured by stopped flow CO2 hydration assay
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 337.38, ALogP 1.2, HBA 4, HBD 3, PSA 101.29, QED 0.74