lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccccc2F)cc(OC)c1OC
InChIKey: WNVRTMGRXBPZGW-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 485.56, ALogP 3.61, HBA 6, HBD 2, PSA 89.13, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(Oc2ccc(F)c(Cl)c2)c(CN2CCNCC2)c1
InChIKey: AUZPDOKGNIPUKF-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Agonist activity at His6-tagged-human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli BL21-CodonPlus-RIPL cells assessed as increase in SOS1-mediated GDP/GTP nucleotide exchange upon K-Ras G12D mutant (1 to 169 residues) by BODIPY-GDP assay
Measurement: EC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 399.88, ALogP 2.32, HBA 5, HBD 2, PSA 84.66, QED 0.81
Compound (SMILES): CCCCCCN(CCCCCC)CC(=O)N(CCC(=O)O)CCc1ccc(S(N)(=O)=O)cc1
InChIKey: DJQVHAFUQICALS-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 585.7 nM (pChEMBL 6.230000019073486)
Descriptors: MW 497.7, ALogP 3.64, HBA 5, HBD 2, PSA 121.01, QED 0.28
Compound (SMILES): N#C[C@@H]1C[C@H]1C(=O)N[C@@]12C[C@@H]1CN(c1nc(Nc3cnn(CCO)c3)ncc1F)C2
InChIKey: OCNRQCROIYCWQL-QULAYQROSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human recombinant JAK1 assessed as level of phosphorylation in presence of peptide substrate 5FAM-KKSRGDYMTMQUID and ATP by mobility shift assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 412.43, ALogP 0.4, HBA 9, HBD 3, PSA 131.99, QED 0.6
Compound (SMILES): COc1ccc(-c2[nH]c3ccc(C4CCN(C(C)=O)CC4)cc3c2C)cc1OC
InChIKey: UPDYWYFZJKAQDZ-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 392.5, ALogP 4.89, HBA 3, HBD 1, PSA 54.56, QED 0.69
Compound (SMILES): Cc1cccc2nc(-c3cccc(NC(=O)CCCc4ccccc4)c3)[nH]c12
InChIKey: NTROMPLHPUUKSF-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 40900 nM (pChEMBL 4.389999866485596)
Descriptors: MW 369.47, ALogP 5.5, HBA 2, HBD 2, PSA 57.78, QED 0.47
Compound (SMILES): CSc1nc2ccccc2n1-c1csc(NCC(C)=O)n1
InChIKey: DHBMOABPBBTTBA-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 318.43, ALogP 3.2, HBA 7, HBD 1, PSA 59.81, QED 0.73
Compound (SMILES): Nc1nc(N2CCN(c3ccc(S(N)(=O)=O)cc3)CC2)nc2sc(-c3ccco3)nc12
InChIKey: UKAIQCQVGWACLI-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241383 from human A2AR expressed in CHO cells by competitive binding assay
Measurement: Ki = 5.73 nM (pChEMBL 8.239999771118164)
Descriptors: MW 457.54, ALogP 1.9, HBA 10, HBD 2, PSA 144.47, QED 0.47
Compound (SMILES): O=C(NCc1ccc(F)cc1)[C@@H]1Cc2c([nH]c3ccccc23)CN1
InChIKey: LRVUOCABDZPTEL-KRWDZBQOSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in HEK-293/TRPM8 exon1 K3 cells assessed as inhibition of menthol-induced current response by whole-cell voltage clamp method
Measurement: IC50 = 36.85 nM (pChEMBL 7.429999828338623)
Descriptors: MW 323.37, ALogP 2.64, HBA 2, HBD 3, PSA 56.92, QED 0.69
Compound (SMILES): CCCCCc1cc(OCCCCCCCCCCC(=O)NC2CC2)cc(OC(C)C)c1
InChIKey: UNJTZCBUUXFOBZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 445.69, ALogP 7.37, HBA 3, HBD 1, PSA 47.56, QED 0.23
Compound (SMILES): C[N@+]12CC[C@H](CC1)[C@@H](OC(=O)Nc1ccccc1-c1ccccc1)C2.O=C([O-])C(F)(F)F
InChIKey: RTRVRBYWISDNTN-SQFUCIKYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 337.44, ALogP 4.14, HBA 2, HBD 1, PSA 38.33, QED 0.85
Compound (SMILES): CC1(C)OB(c2ccc3nc4n(c(=O)c3c2)-c2ccc(F)cc2C4=O)OC1(C)C
InChIKey: NIRSZJKISIXDDH-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 392.2
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)C2)cc1F
InChIKey: APFZUNBSYNZMFG-QGZVFWFLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 = 5540 nM (pChEMBL 5.260000228881836)
Descriptors: MW 543.69, ALogP 5.7, HBA 8, HBD 2, PSA 100.36, QED 0.28
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCCC(C)(C)C#N)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: NDUQBOOKZMSFRQ-ZDUSSCGKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 672.55, ALogP 5.59, HBA 7, HBD 2, PSA 132.26, QED 0.33
Compound (SMILES): Nc1cccc(-c2cn3ccnc3c(Nc3ccc(N4CCN(C5COC5)CC4)cc3)n2)c1
InChIKey: KFLYQNSJGKRCNU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 441.54, ALogP 3.24, HBA 8, HBD 2, PSA 83.95, QED 0.46
Compound (SMILES): CCO[C@H]1CCN(Cc2c(C)cc(C)c3[nH]ccc23)[C@H](c2ccc(C(=O)O)cc2)C1
InChIKey: NHSANTONQVVKKW-REWPJTCUSA-N
Target: Complement factor B (SINGLE PROTEIN), Homo sapiens
UniProt: P00751
Assay: Inhibition of serine protease factor B in 50% human whole blood assessed as reduction in alternative pathway-mediated membrane attack complex formation pre-incubated for 15 mins before activated zymosan A stimulation for 50 mins by ELISA
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 406.53, ALogP 5.23, HBA 3, HBD 2, PSA 65.56, QED 0.59
Compound (SMILES): C=C1CC(c2ccccc2)(C(Br)c2ccccc2)OC1=O
InChIKey: VCACYUXUEIWWBL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin)
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 343.22, ALogP 4.52, HBA 2, HBD 0, PSA 26.3, QED 0.47
Compound (SMILES): CCCCCc1cc(OC)cc(OCCCCCCCCCCC(=O)NC2CC2)c1
InChIKey: IGGCLPHXCBCRCJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 417.63, ALogP 6.6, HBA 3, HBD 1, PSA 47.56, QED 0.27
Compound (SMILES): CN(c1ccnc(Nc2ccc(C(=O)O)cc2)n1)C1CCCCC1
InChIKey: SNXSBHRORYNWID-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 326.4, ALogP 3.69, HBA 5, HBD 2, PSA 78.35, QED 0.87
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(OCc5c(F)cccc5C(F)(F)F)cc4CC[C@@H]23)CC1
InChIKey: XHOQKASAZIGDAE-KYNBKCAXSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Agonist activity at Gal4-fused RORalpha (unknown origin)
Measurement: EC50 = 8400 nM (pChEMBL 5.079999923706055)
Descriptors: MW 677.69, ALogP 6.67, HBA 5, HBD 1, PSA 100.98, QED 0.22
Compound (SMILES): Cn1cc(-c2cnc(N)c(Oc3ccc(C(=O)Nc4cccc(Cl)c4)cc3)n2)cn1
InChIKey: WEOGGUARIACEDQ-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora kinase B (unknown origin) incubated for 30 mins by Kinase Glo luminescent assay
Measurement: IC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 420.86, ALogP 4.16, HBA 7, HBD 2, PSA 107.95, QED 0.5
Compound (SMILES): COc1cccc(Cn2cnc3sc(-c4ccnc(C)c4)cc3c2=O)c1
InChIKey: CYTJYFCWFSYKPU-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant human ROCK2 (11 to 552 residues) using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 40 mins in presence of [gamma-33P]ATP by radiometric scintillation assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 363.44, ALogP 3.89, HBA 6, HBD 0, PSA 57.01, QED 0.55
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)C1CCCC1
InChIKey: PFQCUMURCZHTBY-NNDBWJOKSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing protease cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 1.18 nM (pChEMBL 8.930000305175781)
Descriptors: MW 623.75, ALogP 3.48, HBA 8, HBD 4, PSA 144.45, QED 0.27
Compound (SMILES): Fc1ccc(CN2CCCN(C(=S)Nc3cc(F)cc(F)c3)C2)cc1
InChIKey: YIJMQARSZOHNOV-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-DTG from recombinant sigma 2 receptor (unknown origin) expressed in baculovirus infected Sf9 cell membranes after 1.5 hrs by scintillation counting analysis
Measurement: Ki = 949 nM (pChEMBL 6.019999980926514)
Descriptors: MW 365.42, ALogP 3.97, HBA 2, HBD 1, PSA 18.51, QED 0.83
Compound (SMILES): C[C@@H]1C[C@H]1CNC(=O)[C@@H]1C[C@H]1[C@]12COC[C@H]1CSC(N)=N2
InChIKey: FKPBYKKZZCOMKI-MIDHOLSSSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2
Measurement: IC50 = 1580 nM (pChEMBL 5.800000190734863)
Descriptors: MW 309.44, ALogP 0.84, HBA 5, HBD 2, PSA 76.71, QED 0.81
Compound (SMILES): COC(=O)[C@H](Cc1ccc(O)cc1)n1cc(COc2nc(Cl)nc(N3CCOCC3)n2)nn1
InChIKey: FIMNKFVUNODWNE-INIZCTEOSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 10 mins followed by substrate addition and measured after 2 mins by EIA assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 475.89, ALogP 1.19, HBA 12, HBD 1, PSA 137.61, QED 0.47
Compound (SMILES): CCN1C(=O)c2ccccc2N(C)c2nc(Nc3ccc(NS(C)(=O)=O)cc3OC)ncc21
InChIKey: JVVFSGBLMWRDED-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 catalytic domain (970 to 2527 residues) expressed in baculovirus expression system using LRRKtide as substrate measured after 1 hr by Alexa fluor-647 ADP tracer-based ADAPTA assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 468.54, ALogP 3.35, HBA 8, HBD 2, PSA 116.76, QED 0.57
Compound (SMILES): COc1ccc(-c2cnn3c(N)c(-c4ccccc4)c(NC4CC(C)(C)N(C)C(C)(C)C4)nc23)cc1OC
InChIKey: YRBWLEAMGAGYBK-UHFFFAOYSA-N
Target: TEL/KDR (CHIMERIC PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 514.67, ALogP 5.73, HBA 8, HBD 2, PSA 89.94, QED 0.34
Compound (SMILES): NC(=O)[C@H]1CC[C@H](c2ccc(OCc3ccccc3F)cc2)N1
InChIKey: JESCETIFNOFKEU-IAGOWNOFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 314.36, ALogP 2.68, HBA 3, HBD 2, PSA 64.35, QED 0.89
Compound (SMILES): COc1c2c(cc3c1OCO3)[C@]13C=C[C@H](OC)C[C@@H]1[N@](C2)C[C@H]3OC(=O)c1ccoc1
InChIKey: XIDPCYQOYQJDJP-GFBHRSBTSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate measured for 1 min by spectrophotometric based Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 425.44, ALogP 2.65, HBA 8, HBD 0, PSA 79.6, QED 0.55
Compound (SMILES): CN(C)C[C@@H]1COC[C@](c2ccccc2)(C2CCCCC2)O1
InChIKey: UOKGNINOAYOIDX-MOPGFXCFSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 67.61 nM (pChEMBL 7.170000076293945)
Descriptors: MW 303.45, ALogP 3.44, HBA 3, HBD 0, PSA 21.7, QED 0.85
Compound (SMILES): CCC(=O)O[C@@H]1C[N@@]2Cc3c(cc4c(c3OC)OCO4)[C@@]13C=C[C@H](OC)C[C@H]23
InChIKey: OEQIACMXZJPJNX-VPKASPSASA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate measured for 1 min by spectrophotometric based Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.43, ALogP 2.16, HBA 7, HBD 0, PSA 66.46, QED 0.58
Compound (SMILES): COc1cc(CN(C)C(=O)c2c(OCCCC3CCN(C(=O)OC4(C)CC4)CC3)c3cccnc3n(C)c2=O)cc(OC)c1
InChIKey: MAESKLOMCRHIFV-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D4B1
Assay: Inhibition of mouse recombinant C-terminal FLAG-tagged SMS2 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 606.72, ALogP 4.78, HBA 9, HBD 0, PSA 112.43, QED 0.29
Compound (SMILES): Cc1ccccc1-n1ncc2c1CCC[C@H]2NC(=O)c1onc2c1CCCC2
InChIKey: NFPIDIDBNBMILG-QGZVFWFLSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition Assay: Assay B: Example compounds as described herein were dispensed with an acoustic liquid handler, Echo 550 (Labcyte) to a maximum volume of 50 nl per well in a 384 well plate. DHODH enzyme assays were performed with 4 nM recombinant human DHODH (purified essentially as described by Walse et. al., Biochemistry, 47, 8929-8936 (2008)). The reaction mixture consisted of 2 mM DL-dihydroorotic acid (#D7003, Sigma-Aldrich), 100 μM 3,4-dimethoxy-5-methyl-p-benzoquinone (#D9150, Sigma-Aldrich), and 200 μM 2,6-dichlorophenolindophenol sodium salt (DCIP) (#D1878, Sigma-Aldrich) in enzyme buffer (50 mM Tris-HCl pH 8.0, 0.1% Triton X-100, 150 mM KCl) in a final volume of 50 μl per well. A stock solution of 80 mM DCIP was prepared in DMSO just before use. Loss in absorbance by chromogen DCIP was measured at 595 nm at RT every 2 min for an hour with a plate reader (Envision, Perkin Elmer).
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 376.46, ALogP 3.85, HBA 5, HBD 1, PSA 72.95, QED 0.75
Compound (SMILES): CCCCCN(CCCCC)CCC(=O)N(CCc1ccc(S(N)(=O)=O)cc1)Cc1ccccc1
InChIKey: GWVOOCRAGFOHPW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 522.6 nM (pChEMBL 6.28000020980835)
Descriptors: MW 501.74, ALogP 4.98, HBA 4, HBD 1, PSA 83.71, QED 0.31
Compound (SMILES): CCn1c(-c2ccc(F)cc2)cs/c1=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: IAMXXYYAVOBNDV-LVZFUZTISA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 75.1 nM (pChEMBL 7.119999885559082)
Descriptors: MW 377.47, ALogP 3.26, HBA 5, HBD 1, PSA 77.45, QED 0.76
Compound (SMILES): N[C@@H](CCCCCC(=O)c1ccon1)c1ncc(-c2ccccc2F)[nH]1
InChIKey: NRXMHGVXTYHHEY-HNNXBMFYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 356.4, ALogP 4.04, HBA 5, HBD 2, PSA 97.8, QED 0.45
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cn([C@H](C)c2ccccc2)c1=O
InChIKey: AYQUCQJYWKQBRS-GFCCVEGCSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 12589.25 nM (pChEMBL 4.900000095367432)
Descriptors: MW 339.4, ALogP 1.71, HBA 4, HBD 2, PSA 80.2, QED 0.87
Compound (SMILES): c1cc2c3c(c1)CNCCN3CCCC2
InChIKey: IIDVYPGENCGNCI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 905 nM (pChEMBL 6.039999961853027)
Descriptors: MW 202.3, ALogP 1.93, HBA 2, HBD 1, PSA 15.27, QED 0.69
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(CN4C(=O)CCC4=O)sc23)c1O[C@@H]1CCNC[C@@H]1C
InChIKey: TZRCZTLMNKIMSY-YCRPNKLZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of USP7 in human RKO cells transfected with p53 luciferase reporter vector assessed as increase in p53-dependent luciferase activity measured after 18 hrs by BrightGlo luciferase assay
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 484.02, ALogP 4.95, HBA 6, HBD 1, PSA 71.53, QED 0.52
Compound (SMILES): C=C1COC[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3n[nH]c(N)n3)CC2)C1
InChIKey: UBSCRCKRFRSUEI-SFHVURJKSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 402.93, ALogP 2.51, HBA 6, HBD 2, PSA 83.3, QED 0.76
Compound (SMILES): Nc1nc(N2CCC(N(Cc3ccccc3)[C@H](CO)Cc3ccc(Cl)cc3)CC2)n[nH]1
InChIKey: UNLAZLHBHLHHMA-NRFANRHFSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 440.98, ALogP 3.11, HBA 6, HBD 3, PSA 94.3, QED 0.5
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccc(Oc2ncccn2)cc1
InChIKey: NTZSNJSBXHYURP-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 389.46, ALogP 3.52, HBA 5, HBD 1, PSA 81.18, QED 0.54
Compound (SMILES): CN(C[C@@]12CC[C@@H](O)[C@@H]1CC(CCCCCCCCCC(=O)O)=C2c1ccccc1)c1ccccc1
InChIKey: NHGHHCUVTALBNH-LBRLCBGXSA-N
Target: Nuclear receptor subfamily 5 group A member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00482
Assay: Agonist activity at LRH1 (unknown origin) by luciferase reporter gene assay
Measurement: EC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 489.7, ALogP 7.33, HBA 3, HBD 2, PSA 60.77, QED 0.27
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(N)=O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: QAHDDKVDYBCKJA-QMMMGPOBSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 577.41, ALogP 4.02, HBA 6, HBD 2, PSA 122.46, QED 0.5
Compound (SMILES): COc1ccc(NC(=O)CN2[C@@H]3CCC[C@H]2C[C@H](NC(=O)c2cc(OC)c(OC)c(OC)c2)C3)cc1
InChIKey: OHGNYEANIDSCBZ-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 497.59, ALogP 3.48, HBA 7, HBD 2, PSA 98.36, QED 0.55
Compound (SMILES): O=C(O)C(=O)O.c1ccc(CC2CCN(C[C@@H]3CS[C@@]4(CCCc5ccccc54)S3)CC2)cc1
InChIKey: HSEMCHHGBXBSPS-BUDDBBPTSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-ditolylguanidine from human Sigma 2 receptor by radioligand displacement assay
Measurement: Ki = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 409.66, ALogP 5.98, HBA 3, HBD 0, PSA 3.24, QED 0.61
Compound (SMILES): NC(=O)[C@@H]1CC[C@H](c2ccc(OCc3cccc(F)c3)cc2)N1
InChIKey: COZIWLKAUWUAJD-SJORKVTESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 314.36, ALogP 2.68, HBA 3, HBD 2, PSA 64.35, QED 0.89
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2cc(Oc3cn(C4CC4)nc3C3CCOCC3)ccn2)c1
InChIKey: RYCJKBMIUYEPJJ-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) expressed in mouse NIH/3T3 cells by cell-based luciferase assay
Measurement: IC50 = 167.7 nM (pChEMBL 6.78000020980835)
Descriptors: MW 455.54, ALogP 3.69, HBA 8, HBD 2, PSA 121.36, QED 0.56
Compound (SMILES): O=c1n(CCCCN2CCN(c3cccc4sccc34)CC2)nc2c(F)cccn12
InChIKey: FJLHVGCNLNMUSS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 425.53, ALogP 3.45, HBA 7, HBD 0, PSA 45.78, QED 0.44
Compound (SMILES): Br.Br.NCCCCCc1c[nH]cn1
InChIKey: QSDXAAWBBPWGEL-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]-N-alpha-methylhistamine from Galphai2/Gbeta1gamma2-coupled human recombinant H3R expressed in baculovirus infected Sf9 insect cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 37.15 nM (pChEMBL 7.429999828338623)
Descriptors: MW 153.23, ALogP 1.08, HBA 2, HBD 2, PSA 54.7, QED 0.62
Compound (SMILES): COc1cc(C)c(CNC(=O)c2c(C)n([C@H](C)C3CCN(CC(F)(F)F)CC3)c3ccccc23)c(=O)[nH]1
InChIKey: BCFKADGTTCERFH-QGZVFWFLSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 in human HeLa cells assessed as inhibition of trimethylation of H3K27 after 72 hrs by AlphaLISA assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518.58, ALogP 4.72, HBA 5, HBD 2, PSA 79.36, QED 0.47
Compound (SMILES): O=C(CCc1ccc(OCc2ccccc2)cc1)NCC1CCN(Cc2cccs2)CC1
InChIKey: AUCUDIHVOWJNEE-UHFFFAOYSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of recombinant human full length C-terminal His6-tagged LTA4H expressed in Escherichia coli BL21 DE3 cells assessed as reduction in amino-4-methylcoumarin formation using L-arginine-7-amino-4-methylcoumarin as substrate incubated for 30 mins followed by substrate addition and measured for 30 mins by fluorescence based assay
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 448.63, ALogP 5.29, HBA 4, HBD 1, PSA 41.57, QED 0.46
Compound (SMILES): CC1CN(c2cccnc2)C(=O)c2ccc(Cl)cc21
InChIKey: RLAVMOGTUJEIEJ-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycortisol as substrate by HTRF assay
Measurement: IC50 = 2588 nM (pChEMBL 5.590000152587891)
Descriptors: MW 272.74, ALogP 3.5, HBA 2, HBD 0, PSA 33.2, QED 0.8
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(Cn3ccnn3)cc1c2=O
InChIKey: WKUCZEJPWUVYSN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 347.31, ALogP 1.71, HBA 7, HBD 0, PSA 82.67, QED 0.49
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(Cc1ccccc1)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: ZLSLOZARWUIXQE-BHYZAODMSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 607.8, ALogP 7.02, HBA 6, HBD 2, PSA 100.21, QED 0.15
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@H](c2ccc([S+]([O-])c3ccccc3)cc2)O1.[I-]
InChIKey: KPHVEMVYBZLRAI-RUXQPZOXSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 3019.95 nM (pChEMBL 5.519999980926514)
Descriptors: MW 360.5, ALogP 3.02, HBA 3, HBD 0, PSA 41.52, QED 0.61
Compound (SMILES): N#Cc1ccc2nn(CCCCN3CCN(c4cccc5sccc45)CC3)c(=O)n2c1
InChIKey: LDAHGSIPSNYPMF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 432.55, ALogP 3.18, HBA 8, HBD 0, PSA 69.57, QED 0.44
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cccc(F)c1O
InChIKey: OGACTSAOCINRLN-UHFFFAOYSA-N
Target: P2X purinoceptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBL9
Assay: Antagonist activity at human P2X2 receptor expressed in human 1321N1 cells assessed as inhibition of ATP-induced cytosolic calcium influx preincubated for 30 mins followed by ATP addition by Fluo-4 AM dye-based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 367.22, ALogP 4.82, HBA 2, HBD 2, PSA 49.33, QED 0.75
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3Cc2ccc(Cl)cc2)cc(OC)c1OC
InChIKey: BCMJACCJDMVBOI-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 38600 nM (pChEMBL 4.409999847412109)
Descriptors: MW 458.99, ALogP 4.68, HBA 5, HBD 1, PSA 60.03, QED 0.65
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc4ccc(O)c(I)c4)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)CNC(=O)[C@@H](N)CCC(=O)NCCCC[C@H](C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC3=O)C(=O)N2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC1=O
InChIKey: VXJKUKUEMCMGCD-OWNSCWIHSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response measured after 5 mins by two electrode voltage-clamp assay
Measurement: IC50 = 504 nM (pChEMBL 6.300000190734863)
Descriptors: MW 1928.96
Compound (SMILES): C[C@H]1COc2c(N3CCN(C)CC3)c(F)cc3c(=O)c(C(=O)NCc4cn(CCCCCCCC(=O)NO)nn4)cn1c23
InChIKey: OQWYUSYVASSTHM-IBGZPJMESA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2 incubated for 30 mins by SpectraMax M2 microplate reader analysis
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 598.68, ALogP 2.21, HBA 11, HBD 3, PSA 146.85, QED 0.16
Compound (SMILES): COc1ccccc1C(=O)O[C@@H]1C[N@@]2Cc3c(cc4c(c3OC)OCO4)[C@@]13C=C[C@H](OC)C[C@H]23
InChIKey: KPQIGUOJWACERQ-UWSLFPQHSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate measured for 1 min by spectrophotometric based Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 465.5, ALogP 3.07, HBA 8, HBD 0, PSA 75.69, QED 0.49
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccccc4C#N)c(C)c3c2)CC1
InChIKey: WVCWAGRCNAPJQO-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 372.52, ALogP 4.41, HBA 3, HBD 2, PSA 54.85, QED 0.7
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCC[C@H]3c2ccc(F)c(F)c2F)ncn1
InChIKey: XGTZKVXMDSWEOE-FIEAQMJYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of human gamma secretase expressed in HEK293 cells assessed as reduction in total amyloid beta (1 to 42 residues) production
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 483.54, ALogP 4.44, HBA 7, HBD 1, PSA 71.76, QED 0.55
Compound (SMILES): CC(C)c1cnn2c(NCc3ccccc3)cc(N[C@@H](CO)[C@@H](O)CO)nc12
InChIKey: KRIWIRSMQRQYJG-IRXDYDNUSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 385.47, ALogP 1.59, HBA 8, HBD 5, PSA 114.94, QED 0.38
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccc(Oc2cnccn2)cc1
InChIKey: ACONZWOERUMDPD-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 389.46, ALogP 3.52, HBA 5, HBD 1, PSA 81.18, QED 0.54
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCCCCCCNc1c(NCCCOc2cccc(CN3CCCCC3)c2)c(=O)c1=O.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: OAVRHILPUHUKOZ-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Binding affinity to human H2R expressed in human HEK293T cells incubated for 90 mins by flowcytometry
Measurement: Kd = 18.62 nM (pChEMBL 7.730000019073486)
Descriptors: MW 719.01, ALogP 7.91, HBA 7, HBD 2, PSA 77.79, QED 0.04
Compound (SMILES): COc1ccc(OCC2c3ccc(OC)cc3CC(=O)N2CCCC(F)(F)F)cc1
InChIKey: QBPOCYLWPVBMKO-UHFFFAOYSA-N
Target: Ionotropic glutamate receptor NMDA 1/2D (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q62645
Assay: Positive allosteric modulation of recombinant rat GluN1a/GluN2D receptor expressed in Xenopus laevis oocytes assessed as increase in glycine/L-glutamate-induced channel current by two-electrode voltage clamp method
Measurement: EC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 423.43, ALogP 4.55, HBA 4, HBD 0, PSA 48, QED 0.63
Compound (SMILES): CCCCCc1cc(OC)cc(OCCCCCCCCCCC(=O)Nc2ccccc2)c1
InChIKey: LVLNAKZYJONYRP-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 308.9 nM (pChEMBL 6.510000228881836)
Descriptors: MW 453.67, ALogP 7.96, HBA 3, HBD 1, PSA 47.56, QED 0.23
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2ccnc(SCC(=O)c3ccccc3)n2)cc1
InChIKey: QYCQDQHPLJIDJD-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 400.49, ALogP 2.84, HBA 7, HBD 2, PSA 115.04, QED 0.36
Compound (SMILES): CC(C)=CCCC1=CC[C@@H](C(=O)Nc2ccc(O)cc2)[C@H](c2ccccc2)C1
InChIKey: YHTHEHWLTPHYSR-RPWUZVMVSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 375.51, ALogP 6.2, HBA 2, HBD 2, PSA 49.33, QED 0.47
Compound (SMILES): CCOC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@](Cl)(Br)[C@@H]1O)Oc1ccccc1
InChIKey: BIDXGMZPYDTZTP-DPWGDBROSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase in HCV genotype 1b Con1 infected in human HuH7 replicon cells assessed as inhibition of viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 301 nM (pChEMBL 6.519999980926514)
Descriptors: MW 596.76, ALogP 1.87, HBA 10, HBD 3, PSA 158.18, QED 0.21
Compound (SMILES): Cn1nccc1CCOc1cc(F)c(S(=O)(=O)Nc2ncns2)cc1F
InChIKey: RUZRQWYTSWEZCR-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 401.42, ALogP 1.97, HBA 8, HBD 1, PSA 99, QED 0.65
Compound (SMILES): COc1cccn2c(=O)n(CCCCN3CCN(c4cccc5sccc45)CC3)nc12
InChIKey: LZDIMLIVNXMYDQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 437.57, ALogP 3.32, HBA 8, HBD 0, PSA 55.01, QED 0.42
Compound (SMILES): CCCCCc1cc(OC)cc(OCCCCCCCC(=O)NCCO)c1
InChIKey: XEDRMGXWQVXEAF-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 41.9 nM (pChEMBL 7.380000114440918)
Descriptors: MW 379.54, ALogP 4.26, HBA 4, HBD 2, PSA 67.79, QED 0.42
Compound (SMILES): Cc1noc(C)c1-c1cc2ncc3c(c2cc1OCC1CCNCC1)n(C(C)c1ccccn1)c(=O)n3C
InChIKey: RFECQGJZSWPOFA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged human BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant expressed in Escherichia coli after 1 hr by TR-FRET assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 512.61, ALogP 4.54, HBA 9, HBD 1, PSA 100, QED 0.36
Compound (SMILES): CCCc1c(NCc2ccccc2N2CCN(C)CC2)cnn(C)c1=O
InChIKey: KXTYYTPPRXLSCY-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to human partial length BRPF1 (E627 to G740 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 355.49, ALogP 2.1, HBA 6, HBD 1, PSA 53.4, QED 0.86
Compound (SMILES): O=C(NC1CC1)c1ccc(-c2cnc3c(NCCO)nccn23)cc1
InChIKey: JIWXRIDKNPUWBG-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 8780 nM (pChEMBL 5.059999942779541)
Descriptors: MW 337.38, ALogP 1.69, HBA 6, HBD 3, PSA 91.55, QED 0.64
Compound (SMILES): Cc1ccc(C)c(NCCN2CC[C@@]3(C)c4cc(O)ccc4C[C@@H]2[C@@H]3C)c1
InChIKey: FNOVFQXCGMSHOV-NTUVXCKYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from DOR in rat brain membranes incubated for 45 mins by liquid scintillation counting
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 364.53, ALogP 4.65, HBA 3, HBD 2, PSA 35.5, QED 0.83
Compound (SMILES): COc1ccc2nc(NC(=O)c3cccc(C)c3)sc2c1
InChIKey: LJVIDRQEMOHZLB-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 298.37, ALogP 3.87, HBA 4, HBD 1, PSA 51.22, QED 0.8
Compound (SMILES): Clc1ccc(-c2cccn3cc(-c4ccccc4)nc23)cc1
InChIKey: PWFFYDSSTMPMCL-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of human recombinant ALDH1A3 pre-incubated for 5 mins before acetaldehyde addition by continuous spectrometric assay relative to control
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 304.78, ALogP 5.32, HBA 2, HBD 0, PSA 17.3, QED 0.49
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccc(F)cc5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: USWPMAVZJDCAQR-RJKGWOMYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 3.42 nM (pChEMBL 8.470000267028809)
Descriptors: MW 588.72, ALogP 6.95, HBA 5, HBD 1, PSA 54.82, QED 0.23
Compound (SMILES): O=C(Nc1ccc(C23CC4CC(CC(C4)C2)C3)cc1)c1ccc(CN2CCCCC2)cc1
InChIKey: PXTNFCFIQPMKAS-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant human CYP2C9 expressed in baculovirus infected insect cell microsomes using vivid BOMF as substrate preincubated for 10 mins followed by substrate addition and measured after 25 mins in presence of NAD+ by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 428.62, ALogP 6.39, HBA 2, HBD 1, PSA 32.34, QED 0.6
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CC(F)(F)C[C@@H]2C)c(Cl)c1Cl)C(F)(F)F
InChIKey: JJKXCDSVZIHACK-QWRGUYRKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 667.51, ALogP 4.72, HBA 7, HBD 3, PSA 128.7, QED 0.35
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(CCCOc4ccc5ccc(=O)oc5c4)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: JDECMPHXKKFPMS-CEWLAPEOSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 495.49, ALogP 1.08, HBA 11, HBD 2, PSA 154.47, QED 0.27
Compound (SMILES): CCN(CC(F)F)C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: LFBSPDQNLRBZNN-JTQLQIEISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 655.5, ALogP 4.57, HBA 7, HBD 3, PSA 128.7, QED 0.3
Compound (SMILES): CN1C(=O)N(c2ccc3[nH]ncc3c2)C2(CCN(C(=O)[C@H](NC(=O)c3cc(C(F)(F)F)ccc3F)C3CCCC3)CC2)C1=O
InChIKey: NDFQOGBANFMFIE-XMMPIXPASA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 614.6, ALogP 4.47, HBA 5, HBD 2, PSA 118.71, QED 0.32
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCN(C(C)C)CC4)cc3)c2C)cc(OC)c1OC
InChIKey: ZDZMGLNKGDDURP-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay
Measurement: IC50 = 2236 nM (pChEMBL 5.650000095367432)
Descriptors: MW 461.61, ALogP 5.28, HBA 6, HBD 0, PSA 47.06, QED 0.48
Compound (SMILES): CC(C)c1cnn2c(NCc3ccccc3-n3cccn3)nc(O[C@H]3CCCNC3)nc12
InChIKey: LSGRZENCFIIHNV-SFHVURJKSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 432.53, ALogP 3.18, HBA 9, HBD 2, PSA 94.19, QED 0.46
Compound (SMILES): COc1nc2ccccc2cc1-c1cnc([C@@H](N)CCCCCC(=O)c2cc[nH]n2)[nH]1
InChIKey: UKNPNNJYGOJZRO-KRWDZBQOSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 418.5, ALogP 4.19, HBA 6, HBD 3, PSA 122.57, QED 0.26
Compound (SMILES): C[C@@H]1[C@@H]2CN(c3nc(Nc4cnn(CCO)c4)ncc3F)C[C@]12NC(=O)[C@@H]1C[C@H]1C#N
InChIKey: LFICXKJWMGNAQX-RRHMTCKMSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human recombinant JAK1 assessed as level of phosphorylation in presence of peptide substrate 5FAM-KKSRGDYMTMQUID and ATP by mobility shift assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 426.46, ALogP 0.65, HBA 9, HBD 3, PSA 131.99, QED 0.59
Compound (SMILES): CCOc1cc(Cl)c(-c2ncc(-c3nc4ccccc4s3)c(=O)[nH]2)cc1N1CCOCC1
InChIKey: NVCVBDIRCUPQJE-UHFFFAOYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-ghrelin from human GHS-R1a stably expressed in HEK cell membrane measured after 60 mins by gamma counter method
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 468.97, ALogP 4.6, HBA 7, HBD 1, PSA 80.34, QED 0.46
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2ccccc2OC)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: ZRFYITKWKPSVFW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 516.55, ALogP 5.93, HBA 4, HBD 3, PSA 92.03, QED 0.16
Compound (SMILES): CCCCCCN(CCCCCC)CC(=O)N(CCCN)CCc1ccc(S(N)(=O)=O)cc1
InChIKey: BNSRXXIXPBNAGL-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 2924.8 nM (pChEMBL 5.53000020980835)
Descriptors: MW 482.74, ALogP 3.52, HBA 5, HBD 2, PSA 109.73, QED 0.29
Compound (SMILES): CC1(C)C(/C=C/C=C/C=C2/N(CCCCCC(=O)NCCNC(=O)CCc3cn(CCCCC4CCN(CC(=O)N5c6ccccc6NC(=O)c6ccccc65)CC4)cn3)c3ccc(S(=O)(=O)O)cc3C2(C)C)=[N+](CCCCS(=O)(=O)[O-])c2ccccc21.O=C(O)C(F)(F)F
InChIKey: NIJGLWFVYGGDHH-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor stably expressed in CHO-K9 cells by radioligand competitive binding assay
Measurement: Ki = 0.7943 nM (pChEMBL 9.100000381469727)
Descriptors: MW 1238.59
Compound (SMILES): Cc1ccccc1Nc1nc(Nc2cc(Cl)ccn2)ncc1Cl
InChIKey: LHPRBIBRVGNOET-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 346.22, ALogP 4.97, HBA 5, HBD 2, PSA 62.73, QED 0.7