lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)n1cc(C(=O)Nc2cc3cc(-c4cncn4C(C)C)ccc3cn2)cn1
InChIKey: SOKCEAXUEAIORP-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 7080 nM (pChEMBL 5.150000095367432)
Descriptors: MW 388.48, ALogP 4.71, HBA 6, HBD 1, PSA 77.63, QED 0.54
Compound (SMILES): COc1cccc2c(N3CCN(c4ccccc4F)CC3)c(C#N)cnc12
InChIKey: IVIYDHTVCLPJQV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Positive allosteric modulation of rat mGlu7 expressed in HEK293 cells co- expressing GIRK assessed as potentiation of L-AP4-induced thallium flux incubated for 140 sec by FluoZin2-AM dye based fluorescence analysis
Measurement: EC50 = 870.96 nM (pChEMBL 6.059999942779541)
Descriptors: MW 362.41, ALogP 3.58, HBA 5, HBD 0, PSA 52.39, QED 0.71
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4C[C@@H](N(C)C)CC4=O)c(C=O)nc32)ncc1C#N
InChIKey: LWBSWJUHXCHFLP-FQEVSTJZSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant non-phosphorylated FGFR4 kinase domain (442 to 753) (unknown origin) expressed in Sf9 insect cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 peptide as substrate in presence of ATP measured after 60 mins by caliper microfluidic mobility shift assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 521.58, ALogP 1.83, HBA 9, HBD 1, PSA 140.99, QED 0.39
Compound (SMILES): COc1cc(S(=O)(=O)CC(=O)N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2S(=O)(=O)C(C)C)n1
InChIKey: UOIPIFGVZNDCCW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M mutant (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 637.18, ALogP 3.36, HBA 11, HBD 2, PSA 150.9, QED 0.34
Compound (SMILES): CO[C@@]12CC[C@@H](NCC(=O)NCC(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: PCHRSAVZQDSMPF-APVKTYTCSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 4.39 nM (pChEMBL 8.359999656677246)
Descriptors: MW 431.49, ALogP -0.01, HBA 7, HBD 4, PSA 120.36, QED 0.5
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ncccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: YFKOUTGKKFPEOH-QGZVFWFLSA-N
Target: Solute carrier organic anion transporter family member 1B3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPD5
Assay: Inhibition of OATP1B3 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4ccc5c(cnn5C)c4)cc3c2)cn1
InChIKey: ZUUIIFQSDQMWET-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 382.43, ALogP 3.77, HBA 6, HBD 1, PSA 77.63, QED 0.52
Compound (SMILES): CNC(=O)c1cncc(-c2cnc(Cl)c(NS(=O)(=O)c3ccccc3)c2)c1
InChIKey: IHWSJFBJORCEAK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PIK3C2alpha by ADP-Glo kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.86, ALogP 2.96, HBA 5, HBD 2, PSA 101.05, QED 0.64
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(=O)n(Cc4ccccc4F)c3)ccc12
InChIKey: DUHHTOOYELYHTE-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of recombinant CYP2B6 (unknown origin) using EFC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.35, ALogP 3.16, HBA 4, HBD 2, PSA 76.7, QED 0.6
Compound (SMILES): CC(=O)Nc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: UCWSDAHSOCIBPK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 0.02512 nM (pChEMBL 10.600000381469727)
Descriptors: MW 482.38, ALogP 4.56, HBA 4, HBD 2, PSA 70.67, QED 0.54
Compound (SMILES): CCC1CCCN(c2nc3ccc(Br)cc3c(C(=O)NCC(CCC(=O)O)c3ccccc3Cl)c2C)C1
InChIKey: ZJUNBYODVQMUCZ-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay
Measurement: IC50 = 0.53 nM (pChEMBL 9.279999732971191)
Descriptors: MW 586.96, ALogP 6.96, HBA 4, HBD 2, PSA 82.53, QED 0.28
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N[C@@H]3CCc4ccccc43)no2)cc1O
InChIKey: IXWUILRSNIQHDM-QGZVFWFLSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Selectivity interaction (ITC) EUB0000731a MLLT1
Measurement: Kd = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 391.43, ALogP 3.17, HBA 5, HBD 2, PSA 95.67, QED 0.71
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: DVAPMYJVUZJNDK-DNVCBOLYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 2.91 nM (pChEMBL 8.539999961853027)
Descriptors: MW 421.52, ALogP 1.1, HBA 8, HBD 2, PSA 117.42, QED 0.76
Compound (SMILES): N[C@H]1CN[C@@](CCCCB(O)O)(C(=O)O)C1
InChIKey: SHQWTXRBVVLSOY-VXNVDRBHSA-N
Target: Arginase-2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P78540
Assay: Biological Activity of Examples 1 to 30: The inhibitory effects of Examples 1 to 30 on the activity of Human Arginase 1 and Arginase 2 activity were quantified by measuring the formation of the thiol group from thioarginine using recombinant Arginase 1 or Arginase 2 produced from E. coli. The thiol group was detected with Ellman's reagent, 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB). DTNB reacts with the thiol to give the mixed disulfide and 2-nitro-5-thiobenzoic acid (TNB) which is quantified by the absorbance of the anion (TNB2−) at 412 nm.The assays were run in clear 384 well plates (Greiner cat no: 781101). Various concentrations of Examples 1 to 30 in 300 nL DMSO were dispensed to assay plates using an Echo acoustic dispenser immediately followed by plate sealing and centrifugation. Two pre-mixes were prepared from reagents thawed immediately before addition to assay plates. Pre-mix one comprised human Arginase 1 or human Arginase 2, at a final concentration of 5 nM and 0.5 mM DTNB in assay buffer, 45 mM HEPES pH7.5, brij 35, 0.045% (w/v) and 100 μM MnCl2. Pre-mix two comprised freshly thawed 0.5 mM thioarginine in assay buffer. Fifteen microlitres of pre-mix one was dispensed to assay plates containing Examples 1 to 30, centrifuged and incubated for 30 minutes at room temperature prior to adding fifteen microlitres of pre-mix two.Assay plates were centrifuged prior to reading absorbance at 412 nm in a Pherastar multi-mode plate reader to collect data at time point 0 (T0). The plates were incubated at room temperature for 60 min prior to reading again to collect data at time point 1 (T1). Data is derived by subtracting the A412 signal measured at T0 (time point 0) from that measured at T1 (time point 1). The data was transformed to % effect using the equation:Compound % effect=100*[(X−min)/(max−min)], where X represents the normalized value for the compound based on the Min (vehicle) and Max (reference compound) inhibition control.
Measurement: IC50 = 16630 nM (pChEMBL 4.78000020980835)
Descriptors: MW 230.07
Compound (SMILES): Cc1cc(-c2ccn3nc(N)nc3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: IBRQJCOMQXDQQV-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 347.42, ALogP 3.04, HBA 5, HBD 1, PSA 76.52, QED 0.79
Compound (SMILES): COc1cccc(O)c1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: BUYXRPOASRGKHF-QFIPXVFZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 555.66, ALogP 5.47, HBA 7, HBD 4, PSA 129.23, QED 0.16
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCC(O)C1
InChIKey: USGWWFWAYIOOFO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 70794.58 nM (pChEMBL 4.150000095367432)
Descriptors: MW 274.36, ALogP 1.42, HBA 3, HBD 1, PSA 43.78, QED 0.91
Compound (SMILES): COCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: ZJPSQGKCYKMKSJ-VOQZNFBZSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at recombinant human S1P3 expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding measured after 45 mins by liquid scintillation counting method
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 425.51, ALogP 4.07, HBA 4, HBD 3, PSA 102.01, QED 0.39
Compound (SMILES): CCCOc1ccc2c(c1[C@H]1C[C@@H]1CN)CCO2.Cl
InChIKey: UWVLPYSRFUDFMR-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 741.31 nM (pChEMBL 6.130000114440918)
Descriptors: MW 247.34, ALogP 2.47, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): COc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: ZBGMKBKMVOGMLL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 520.57, ALogP 6.03, HBA 8, HBD 1, PSA 99.25, QED 0.29
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)[C@H]4CC[C@H](CO)CC4)cc3c2)c1CN1CCCCC1
InChIKey: AFXZSFRQUZCOKK-MXVIHJGJSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening assay for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 M) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))].Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 461.61, ALogP 4.36, HBA 6, HBD 2, PSA 83.28, QED 0.57
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)/C=C/c1nccs1
InChIKey: BHWDYFGTRWGKRI-JXMROGBWSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in human THP1 cells assessed as inhibition of IL-1beta production
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 389.5, ALogP 3.24, HBA 5, HBD 2, PSA 88.16, QED 0.84
Compound (SMILES): O=C(NO)c1ccc(Nc2ccnc3ccccc23)cc1
InChIKey: CRQRFXAGXWHWTJ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 279.3, ALogP 3.1, HBA 4, HBD 3, PSA 74.25, QED 0.51
Compound (SMILES): COc1cc(-c2cn([C@H]3CCc4ccccc4N(CC(F)(F)F)C3=O)nn2)ccc1-n1ccc(C)n1
InChIKey: LMWVEVSLAFDIRE-QFIPXVFZSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: GPCRScan assay: inhibition of D4
Measurement: Ki = 4950.66 nM (pChEMBL 5.300000190734863)
Descriptors: MW 496.49, ALogP 4.53, HBA 7, HBD 0, PSA 78.07, QED 0.41
Compound (SMILES): OC/C=C/[C@H]1[C@@H]2CCC[C@@]1(c1cccc(O)c1)CCN2CCc1ccccc1
InChIKey: FTDOOEOFAZGQEK-ZADLEFMZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Activity at human MOR expressed in U2OS cells co-expressing beta-arrestin2 EFC assessed as beta-arrestin2 EFC recruitment by Tango assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 377.53, ALogP 4.3, HBA 3, HBD 2, PSA 43.7, QED 0.74
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CC[C@@]2(O)c1cn(-c2cccc(O)c2)nn1
InChIKey: CNCYPHLGQIATRW-YWBWYGPRSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at full length human ERbeta receptor assessed as transcriptional activity incubated for 22 to 24 hrs by cell based luciferase reporter gene assay
Measurement: EC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 431.54, ALogP 4.42, HBA 6, HBD 3, PSA 91.4, QED 0.56
Compound (SMILES): COC[C@@H](C)Oc1ccc2c(c1)Cc1cccc(-c3cc(=O)cc(N4CCOCC4)o3)c1S2
InChIKey: SYVQAQHCFMTBNA-QGZVFWFLSA-N
Target: Phosphatidylinositol 3-kinase catalytic subunit type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NEB9
Assay: Inhibition of recombinant full-length human VPS34 incubated for 60 mins by ADP-Glo kinase assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 465.57, ALogP 4.61, HBA 7, HBD 0, PSA 61.14, QED 0.41
Compound (SMILES): COC(=O)N1CC[C@](CO)(Nc2nc(N3CCOCC3)nc(-c3cnc(N)nc3)c2F)C1
InChIKey: RTAAXWKPLMSXJJ-IBGZPJMESA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki < 0.28 nM (pChEMBL 9.553000450134277)
Descriptors: MW 448.46, ALogP 0.11, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): CCc1cc(-c2ccc3c(c2)-c2nnc(Nc4cccc(C(F)(F)F)c4)n2CCO3)ccn1
InChIKey: BKGOKPQNNKWLHW-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 451.45, ALogP 5.72, HBA 6, HBD 1, PSA 64.86, QED 0.43
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of His-tagged recombinant human TEC expressed in baculovirus expression system preincubated for 1 hr by Z'lyte assay
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3c(F)c(OC)cc(OC)c3F)c(=O)n(C)c2n1
InChIKey: PSKWUEAQZZDBSQ-UONOGXRCSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) expressed in KATO -III cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 1172 nM (pChEMBL 5.929999828338623)
Descriptors: MW 487.46, ALogP 1.77, HBA 9, HBD 2, PSA 116.6, QED 0.48
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)CC4)c(F)cn2)C1
InChIKey: ZNUJHRYFOFHSMX-JKSUJKDBSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 427.52, ALogP 3.69, HBA 5, HBD 2, PSA 88.91, QED 0.78
Compound (SMILES): CC[C@H](C)C(=O)N1CCC(NC(=O)Nc2ccc(OC(F)(F)F)c(F)c2)CC1
InChIKey: LHRXHTKENPCGSZ-NSHDSACASA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of sEH in C57BL/6J mouse brain homogenate using 14, 15-EET as substrate preincubated for 10 mins followed by substrate addition by UPLC-MS/MS analysis
Measurement: IC50 = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 405.39, ALogP 3.88, HBA 3, HBD 2, PSA 70.67, QED 0.73
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Nek6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC98
Assay: Inhibition of human NEK6 in presence of ATP at Km level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): CCCCNNC(=O)c1cccnc1
InChIKey: NBKPFBBNYBOQPN-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Allosteric inhibition of HDAC3 in HEK293 cell lysates pre-incubated for 2 hrs before acetylated lysine-aminomethyl coumarin-BOC addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 4676 nM (pChEMBL 5.329999923706055)
Descriptors: MW 193.25, ALogP 1.12, HBA 3, HBD 2, PSA 54.02, QED 0.54
Compound (SMILES): O=C(c1ccc(Cl)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(F)c2)CC1
InChIKey: WQLAYHBUUKJKQO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 616.6 nM (pChEMBL 6.210000038146973)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCCC(NS(C)(=O)=O)C3)cc2)nc2sccc12
InChIKey: WVWGTOGGUMSNSD-GQCTYLIASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 13780 nM (pChEMBL 4.860000133514404)
Descriptors: MW 574.73, ALogP 5.9, HBA 9, HBD 2, PSA 120.24, QED 0.25
Compound (SMILES): O=c1[nH]ncc(N2CCc3c(ncnc3Oc3ccc(F)cc3C(F)(F)F)C2)c1Cl
InChIKey: IQFZADSTVFSHDX-UHFFFAOYSA-N
Target: Short transient receptor potential channel 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y210
Assay: Inhibition of TRPC6 (unknown origin) expressed in HEK293 cells assessed as reduction in OAG stimulated Ca2+ influx by FLIPR assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 441.77, ALogP 3.73, HBA 6, HBD 1, PSA 84, QED 0.62
Compound (SMILES): Cc1ncc(-c2ccc3cnc(NC(=O)C4(F)CC4)cc3c2)n1C
InChIKey: JDBSMBPIDCBURU-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission. Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 710 nM (pChEMBL 6.150000095367432)
Descriptors: MW 324.36, ALogP 3.38, HBA 4, HBD 1, PSA 59.81, QED 0.8
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1ccc(Cl)cc1
InChIKey: JTDCOWMSDVDUOO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 1412.54 nM (pChEMBL 5.849999904632568)
Descriptors: MW 314.82, ALogP 4.12, HBA 2, HBD 1, PSA 32.34, QED 0.92
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2c1CCO2
InChIKey: WGICPLUIQIXVNT-XQKZEKTMSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C INI receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 251.3, ALogP 2.03, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): O=C(N[C@@H](CCCCNC(=O)c1ccccc1O)c1ncc(-c2ccc3ccccc3c2)[nH]1)c1cncs1
InChIKey: NIXOIBDALBDEAM-QHCPKHFHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 525.63, ALogP 5.46, HBA 6, HBD 4, PSA 120, QED 0.18
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccnc(N3CCOCC3)c2F)[nH]1
InChIKey: HWZMSMSAVMLYQH-RPWUZVMVSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 554.71, ALogP 4.27, HBA 7, HBD 2, PSA 103.45, QED 0.38
Compound (SMILES): O=[N+]([O-])/C(Cl)=C/c1ccc([N+](=O)[O-])cc1
InChIKey: YVKSKDUKJHYERJ-VMPITWQZSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human FBPase D127A mutant
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 228.59, ALogP 2.41, HBA 4, HBD 0, PSA 86.28, QED 0.45
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(C)cn2)C1
InChIKey: NDQRCUOYOAPFLR-DLBZAZTESA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 409.53, ALogP 3.47, HBA 5, HBD 2, PSA 88.91, QED 0.81
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@@H]1CCOC[C@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: WTHILFAMRXZBRN-SKBVVQJISA-N
Target: Probable G-protein coupled receptor 34 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPC5
Assay: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 0.75 nM (pChEMBL 9.119999885559082)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): O=C(N[C@@H](CCCCNC(=O)c1c(O)cccc1F)c1ncc(-c2ccc3ccccc3c2)[nH]1)c1cncs1
InChIKey: BBLOAIWXSMVTHJ-QFIPXVFZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 543.62, ALogP 5.6, HBA 6, HBD 4, PSA 120, QED 0.17
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)CN(Cc2ccccc2)C1=O
InChIKey: YCLJTMLYPHXJPM-NETOACFBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 949.13, ALogP -0.84, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): CC(C)Oc1cc(F)cc2c(N3CCN(c4ccccc4F)CC3)c(C#N)cnc12
InChIKey: URGDPHSQVLSJCM-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Displacement of [3H]nisoxetine from recombinant human Dopamine transporter after 120 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 408.45, ALogP 4.5, HBA 5, HBD 0, PSA 52.39, QED 0.64
Compound (SMILES): CC(C)(C)C#CCOC(=O)N[C@@H]1CCN(C(=O)N[C@@H](C(=O)N2CCC[C@H]2c2nc(-c3ccc([C@H]4CC[C@H](NC(=O)c5cnc(CO)cn5)CC4)cc3)c[nH]2)c2ccccc2)C1
InChIKey: PPZFNMYHDWJYEL-SRFGQFSHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of Hepatitis C virus 1a NS5A Q30R mutant
Measurement: EC50 = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 830, ALogP 5.78, HBA 9, HBD 5, PSA 194.77, QED 0.12
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)C4)c(Cl)cn2)C1
InChIKey: KZJSUGHOGMRTFQ-JQXSQYPDSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MV4-11 cells assessed as induction of caspase-3/7 activation measured after 6 hrs followed by Caspase-glo reagent based assay
Measurement: EC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 415.93, ALogP 3.42, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): CNCC[C@H](Oc1cccc(N2CCN(C)CCC2=O)c1)c1cccs1
InChIKey: SOZQYEAKFLBWCU-SFHVURJKSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Displacement of [3H]-nisoxetine from human NET expressed in HEK293 cell membranes incubated for 60 mins by scintillation counting method
Measurement: Ki = 382 nM (pChEMBL 6.420000076293945)
Descriptors: MW 373.52, ALogP 3.15, HBA 5, HBD 1, PSA 44.81, QED 0.81
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccn2)CC1
InChIKey: ZMEGJWWPDKBOER-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as stimulation of beta-arrestin recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 20.89 nM (pChEMBL 7.679999828338623)
Descriptors: MW 409.86, ALogP 3.49, HBA 4, HBD 1, PSA 54.46, QED 0.71
Compound (SMILES): CC(=O)N1CCC(C(=O)N2C[C@@H](c3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)[C@@](C)(c3ccccc3)C2)CC1
InChIKey: YXYVNJXYQMACDG-UKILVPOCSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: SPA Binding Assay: The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA) binding assay. The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM for 10 min at room temperature in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% Glycerol (Sigma Cat # G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined.
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 556.55, ALogP 5.14, HBA 3, HBD 1, PSA 60.85, QED 0.53
Compound (SMILES): Cc1ccc(C#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)c2)s1
InChIKey: LZIKVHXLVMNROK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Binding affinity to human His-tagged LDHA by SPR analysis
Measurement: Kd = 0.0634 nM (pChEMBL 10.199999809265137)
Descriptors: MW 632.76, ALogP 5.79, HBA 8, HBD 2, PSA 128.17, QED 0.21
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccc4Cl)CC3)cc2C1=O
InChIKey: QIMOBLHMKZLPIE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 413.95, ALogP 3.56, HBA 4, HBD 0, PSA 36.02, QED 0.68
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3cc(OC)cc(OC)c3)c(=O)n(C)c2n1
InChIKey: KZGOHFREJPYORJ-RBUKOAKNSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Omnia Assay Protocol for Potency Assessment Against FGFR 4 Enzyme: A 10× stock solution of FGFR4-WT (PR4380C or P3054), (from Invitrogen, Carlsbad, Calif.) corresponding to method a in Table 10, was prepared as described below. Alternatively, a 10× stock solution of FGFR4-WT (F01-11G), (SignalChem, Richmond, BC) corresponding to method b in Table 10, was prepared as described below. A solution of 1.4×ATP (AS001A) and 5× Tyr-Sox conjugated peptide substrate (KNZ3101) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM P3-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of FGFR4 was pipetted into a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.), containing a 0.5 μL volume of 100% DMSO. The serially diluted compounds were prepared on a Tecan EVO100. A second addition of 10 μl of Tyr-Sox FGFR4 substrate was added to each well and the kinase reactions were started with the addition of 35 μL of 1.4×ATP. The reactions were monitored every 71 seconds for 240 minutes at λex360/λem485 in a Synergy plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to −60 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (seconds) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response (Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.)).
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 451.48, ALogP 1.49, HBA 9, HBD 2, PSA 116.6, QED 0.52
Compound (SMILES): COc1ccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)cc1
InChIKey: GCGYVRDXSGMVJW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 455.36, ALogP 4.61, HBA 4, HBD 1, PSA 50.8, QED 0.59
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cnccn2)CC1
InChIKey: PCQQITDIAVWGLB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as stimulation of beta-arrestin recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 410.85, ALogP 2.88, HBA 5, HBD 1, PSA 67.35, QED 0.71
Compound (SMILES): COc1ccc(S(=O)(=O)N2C[C@@H](NS(=O)(=O)c3ccc(-c4ccccc4)cc3)C[C@@H]2C(=O)O)cc1
InChIKey: WJTQOAHAJQKSTM-WMZHIEFXSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 20740 nM (pChEMBL 4.679999828338623)
Descriptors: MW 516.6, ALogP 2.56, HBA 6, HBD 2, PSA 130.08, QED 0.47
Compound (SMILES): CC(C)n1nc2c(c1-c1ccc(F)cc1)CCNCC2
InChIKey: RBYJHELKTYHZNG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-ketanserin from human 5-HT2B receptor by competitive radioligand binding assay
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 273.36, ALogP 2.96, HBA 3, HBD 1, PSA 29.85, QED 0.91
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)/C=C/CN(C)C)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SURRDPSGERGIIM-VOTSOKGWSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 459.6, ALogP 3.98, HBA 7, HBD 1, PSA 79.18, QED 0.54
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(C)(C)F
InChIKey: RMHSPVDIAHEXNT-NSYGIPOTSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 468.6, ALogP 4.5, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): COc1cc(SCc2ccc(CN(C)C)o2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: IVWSMDDTFYCVFZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR (669 to 1210 residues) expressed in baculovirus expression system using Srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 589.14, ALogP 5.94, HBA 10, HBD 3, PSA 121.62, QED 0.17
Compound (SMILES): O=C(Nc1cnn(-c2csc(C(=O)NC3COC3)c2)c1)Nc1ccccc1Cl
InChIKey: FPVKFPPNOMNINZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ATF2 as substrate in presence of ATP by HTRF assay
Measurement: IC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 417.88, ALogP 3.36, HBA 6, HBD 3, PSA 97.28, QED 0.59
Compound (SMILES): CN(C)Cc1nc2ccc(Nc3ncc(Cl)c(Nc4ccccc4C(=O)N(C)C)n3)cc2[nH]1
InChIKey: HHJKVSLHPQFAQK-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST-tagged human FLT3 cytoplasmic domain (564 to 993 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 464.96, ALogP 4.26, HBA 7, HBD 3, PSA 102.07, QED 0.38
Compound (SMILES): O=C1N2C[C@@H](CC[C@H]2F)N1OS(=O)(=O)[O-].[Na+]
InChIKey: UIJIKXQAJBMNIR-JBUOLDKXSA-M
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 240.21, ALogP -0.08, HBA 4, HBD 1, PSA 87.15, QED 0.54
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)Nc1cc2c(N[C@H]3CC[C@H](Nc4ncnc5cc(OC)c(NC(=O)[C@@H]6CCCN6C(=O)[C@@H](NC(=O)[C@H](C)NC)C(C)(C)C)cc45)CC3)ncnc2cc1OC)C(C)(C)C
InChIKey: YIZXATJRZDXIBK-ZOGJLHJXSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1051.31
Compound (SMILES): COc1ccc(-c2cc(C(=O)NC3CCCCCC3)c(OCc3ccc(F)cc3)nc2C)cc1
InChIKey: KHBYMJQCFRCSSX-UHFFFAOYSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 462.57, ALogP 6.24, HBA 4, HBD 1, PSA 60.45, QED 0.42
Compound (SMILES): COc1cc2nc3ccccc3c(Nc3ccc(C(=O)NO)cc3)c2c(OC)c1OC
InChIKey: RXYDUXPNMOBQTR-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 419.44, ALogP 4.28, HBA 7, HBD 3, PSA 101.94, QED 0.24