lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(NCc2cnccn2)ncc1C(=O)N1CCC2(CCOCC2)C1
InChIKey: ZNKDYARBMJGNQA-UHFFFAOYSA-N
Target: Pantetheinase (SINGLE PROTEIN), Homo sapiens
UniProt: O95497
Assay: Enzyme Assay: The test inhibitors were solubilized in DMSO to a stock concentration of 30 mM. On the day of the assay, dose response plates were prepared by diluting the inhibitors in DMSO at compound concentration 200-fold the final in-assay concentration. Intermediate concentrations were prepared by diluting in DMSO in a four-fold series for a total of 11 data points.To prepare a working solution of human vanin-1, the enzyme was diluted to 33.3 pM in the assay buffer consisting of 50 mM Tris-HCl pH=8.0, 50 mM KCl, 0.005% Brij-35 and 1.6 mM cysteamine. To begin the assay 100 nL was transferred from the compound plate to the assay plate. Next, 15 μL of the vanin-1 working solution were transferred to the assay plate. The inhibitor and enzyme were incubated at room temperature for 30 minutes. The enzyme reaction was then initiated by the addition of 5 μL of 200 μM pantetheine 7-amino-4-trifluoromethylcoumarin prepared in assay buffer. The final concentrations in the assay were 25 pM human vanin-1 and 50 uM substrate. The final concentration of DMSO was 0.5%. The assay plates were incubated for 60 minutes and before they were read on a Perkin Elmer EnVision Model 2103 using a 405 nm excitation wavelength and a 510 nm emission wavelength for detection.
Measurement: IC50 > 17589 nM (pChEMBL 4.755000114440918)
Descriptors: MW 368.44, ALogP 1.83, HBA 7, HBD 1, PSA 93.13, QED 0.88
Compound (SMILES): CC[C@H](Nc1c(C#N)c(-c2ccc(-c3cccc(C)c3F)cc2)nc2cnccc12)C(=O)O
InChIKey: DVIVLYHDLNAXAT-NRFANRHFSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Affinity On-target Cellular interaction: (CETSA (intact K-562 cells)) EUB0001565a PIP4K2A
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 440.48, ALogP 5.56, HBA 5, HBD 2, PSA 98.9, QED 0.41
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(N2CC[C@@H]3[C@H]2CN3c2cccnn2)s1
InChIKey: VCDTXROFDBHEIP-HUUCEWRRSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: GLS Enzyme activity assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 393.48, ALogP 1.98, HBA 8, HBD 1, PSA 87.14, QED 0.71
Compound (SMILES): N#CN1CC[C@H](C(=O)Nc2nc3c(s2)CN(C(=O)CN=[N+]=[N-])CC3)C1
InChIKey: KIWKRCCIHSGWQS-VIFPVBQESA-N
Target: Ubiquitin carboxyl-terminal hydrolase isozyme L1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09936
Assay: Inhibition of UCHL1 (unknown origin) using Ub-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured for 1 hr by fluorescence based analysis
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 360.4, ALogP 1.08, HBA 7, HBD 1, PSA 138.09, QED 0.37
Compound (SMILES): C=CC(=O)Nc1ccc2[nH]c(=O)n(C3CCN(Cc4ccc(-c5ccc6c(c5)NC(=O)CO6)cc4)CC3)c2c1
InChIKey: DHRJWFCFMBINAK-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Homogeneous Time Resolved Fluorescence (HTRF) assay (AKT1)
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 523.59, ALogP 4.29, HBA 6, HBD 3, PSA 108.46, QED 0.33
Compound (SMILES): N#CN1CC[C@@H](C(=O)Nc2nc3c(s2)CN(C(=O)CN=[N+]=[N-])CC3)C1
InChIKey: KIWKRCCIHSGWQS-SECBINFHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase isozyme L1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09936
Assay: Inhibition of UCHL1 (unknown origin) using Ub-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured for 1 hr by fluorescence based analysis
Measurement: IC50 = 11100 nM (pChEMBL 4.960000038146973)
Descriptors: MW 360.4, ALogP 1.08, HBA 7, HBD 1, PSA 138.09, QED 0.37
Compound (SMILES): COc1cc(C2Oc3c(O)cc([C@H]4Oc5cc(O)cc(O)c5C(=O)[C@@H]4O)cc3C2CO)ccc1O
InChIKey: BMLIIPOXVWESJG-CMIZNHKFSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]estradiol-17beta-glucuronide uptake after 3 mins by beta-counting
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 482.44, ALogP 2.4, HBA 10, HBD 6, PSA 166.14, QED 0.33
Compound (SMILES): CCCn1cnc(C2C=C(C3=C(c4noc5ccccc45)C(=O)NC3=O)c3ccccc32)c1
InChIKey: PORKDACDIRDJMV-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin)
Measurement: IC50 = 0.73 nM (pChEMBL 9.140000343322754)
Descriptors: MW 436.47, ALogP 4.07, HBA 6, HBD 1, PSA 90.02, QED 0.48
Compound (SMILES): CCCCCC(=O)N[C@H](C(=O)NCc1ccc(CNC(=N)N)cc1)c1ccc(OCc2ccccc2)cc1.O=C(O)C(F)(F)F
InChIKey: ZSBYMYRZOKDVDY-JCOPYZAKSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of Dengue virus serotype 2 NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Nle-Lys-Arg-Arg-Ser-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition and measured for 15 mins by FRET assay
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 515.66, ALogP 4.3, HBA 4, HBD 5, PSA 129.33, QED 0.12
Compound (SMILES): CCN1C[C@]2(OC(=O)c3ccccc3NC(C)=O)CC[C@H](OC)[C@@]34[C@@H]2C[C@@H]([C@@H]13)[C@@]1(O)C[C@H](OC)[C@H]2C[C@@H]4[C@]1(O)[C@H]2OC
InChIKey: NWBWCXBPKTTZNQ-QOQRDJBUSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding affinity of Norditerpenoid Alkaloids at rat neuronal alpha7-type nicotinic acetylcholine receptor
Measurement: IC50 = 96000 nM (pChEMBL 4.019999980926514)
Descriptors: MW 584.71, ALogP 2.22, HBA 9, HBD 3, PSA 126.79, QED 0.41
Compound (SMILES): CC(C)(C)[C@H](NC(=O)C(F)(F)F)C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)N[C@H](C#N)C[C@@H]1CCNC1=O)C2(C)C
InChIKey: LIENCHBZNNMNKG-OJFNHCPVSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 main protease using MCA-AVLQSGFR-Lys(Dnp)-Lys-NH2 as fluorescent substrate preincubated for 10 mins followed by substrate addition and measured every 10 sec for 10 mins by FRET assay
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 499.53, ALogP 1.1, HBA 5, HBD 3, PSA 131.4, QED 0.5
Compound (SMILES): O[C@H]1CCCN[C@@H]1CCCn1cnc2c(Cl)c(Cl)ccc21
InChIKey: VXCNMWNXDDMFSX-YPMHNXCESA-N
Target: Ribose-phosphate pyrophosphokinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P60891
Assay: PRS Enzyme Activity Inhibition Experiment: In order to confirm the biological activities of the compounds prepared in Examples, % inhibition or IC50 values of PRS enzyme (phosphoribosylpyrophosphate synthetase enzyme) activities were calculated.Specifically, the portion corresponding to PRS in cDNA of EPRS was subcloned, and the obtained high-purity PRS protein was purified and used in the experiment. The compounds (1 μM) prepared in Examples were added into the reaction buffer (20 mM KPO4 (pH 7.4), 6 mM MgAc, 5 mM ATP, 400 mg/mL tRNA, 0.5 mM DTT, 20 mCi[3H]proline (1 mCi/mL)) and allowed to react at 37° C. for 5 to 10 minutes. The reaction was terminated with 3M paper that was in advance dried by addition of 5% TCA. The radioactivity was measured using a liquid scintillation counter.% Inhibition and IC50 values of the respective compounds were calculated and analyzed using Microsoft Excel or Sigma Plot 8.0.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 328.24, ALogP 3.24, HBA 4, HBD 2, PSA 50.08, QED 0.91
Compound (SMILES): CCCn1cc(-n2c(Cl)c(Sc3cccc(C(=O)O)c3F)c3ccc(Cl)c(F)c32)cn1
InChIKey: NMDFAQXLJQRHMS-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Human Autotaxin Assay: ATX activity is assayed in concentrated conditioned media from Hep3B human hepatocellular carcinoma cells by measuring the amount of choline released from the substrate, lysophosphatidylcholine (LPC) as it is cleaved to LPA. Conditioned media is collected from confluent Hep3B cells and concentrated 20-fold using Centriprep-30 filter devices (Millipore). To assay for autotaxin inhibition, 10-20 μL of the concentrated conditioned media is incubated with 2.5 μL of a test compound in DMSO and 72.5-82.5 μL lyso-PLD buffer (100 mM Tris pH 9, 500 mM NaCl, 5 mM MgCl2, 5 mM CaCl2, 0.05% Triton X-100 in the presence or absence of 0.2% fatty-acid-free human serum albumin) for 15 min at 37° C. After the 15 min incubation, 5 ul of 2 mM LPC (14:0; Avanti Polar Lipids Cat #855575C) diluted in lyso-PLD buffer is added for a final concentration of 100 uM and the incubation continues for 1.5-3 hours at 37° C. 100 μl of a color mix containing 4.5 mM 4-aminoantipyrine, 2.7 mM N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine, 21 units/ml horseradish peroxidase and 3 units/ml choline oxidase in 50 mM Tris, pH 8, 4.5 mM MgCl2 is added and the incubation continued for 15 minutes at room temperature before reading the absorbance at 555 nm.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 482.34, ALogP 6.67, HBA 5, HBD 1, PSA 60.05, QED 0.33
Compound (SMILES): Nc1cc(S(=O)(=O)c2ccc(OC(F)(F)F)cc2)cnc1-c1nnc(CO)o1
InChIKey: WOXOLLSAICIZNO-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Activation of CFTR F508del mutant (unknown origin)
Measurement: EC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 416.34, ALogP 1.94, HBA 9, HBD 2, PSA 141.43, QED 0.64
Compound (SMILES): Cc1c(S(C)(=O)=O)c(-c2cc(F)cc(N3CCN(c4ccc(NS(=O)(=O)c5ccc(N[C@H](CCN6CCC(C(=O)OCCCP(=O)(O)O)CC6)CSc6ccccc6)c(S(=O)(=O)C(F)(F)F)c5)cc4)CC3)c2)c(-c2ccc(Cl)cc2)n1C(C)C
InChIKey: QIOCQCYXBYUYLH-YACUFSJGSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Binding affinity to Bcl-2 (unknown origin) assessed as inhibition constant
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 1281.87
Compound (SMILES): Nc1nnc(CN[C@@H]2C[C@H]2c2ccc(OCc3ccccc3)cc2)o1
InChIKey: XBBRLCXCBCZIOI-DLBZAZTESA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of KDM1A (unknown origin)
Measurement: IC50 = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 336.4, ALogP 2.88, HBA 6, HBD 2, PSA 86.2, QED 0.69
Compound (SMILES): CC(=O)N(C)C1CCN(c2cccc(-c3ccc4nc(-c5cccnc5N)n(-c5ccc(C6(N)CCC6)cc5)c4n3)c2)CC1
InChIKey: NZDSLYATTDIDPH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1 (unknown origin)
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 586.74, ALogP 5.52, HBA 8, HBD 2, PSA 119.19, QED 0.27
Compound (SMILES): C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OS(=O)(=O)O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: PIUZYOCNZPYXOA-ZHHJOTBYSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Antagonist activity at LXRalpha (unknown origin) expressed in HEK293 cells incubated for 24 hrs by TR-FRET assay
Measurement: IC50 = 12600 nM (pChEMBL 4.900000095367432)
Descriptors: MW 482.73, ALogP 6.33, HBA 4, HBD 2, PSA 83.83, QED 0.33
Compound (SMILES): N#Cc1ccc(N2C[C@H](N)C[C@H](C(F)(F)F)C2)c2cccnc12
InChIKey: BJXYHBKEQFQVES-NWDGAFQWSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in HEK-Blue hTLR8 cells assessed as inhibition of TL8-506 induced NF-kappaB activation preincubated with compound for 1 hrs followed by TL8-506 addition and measured after 24 hrs by Quanti-blue reagent based SEAP reporter assay
Measurement: IC50 = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 320.32, ALogP 2.82, HBA 4, HBD 1, PSA 65.94, QED 0.88
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(C4CCNCC4)cn3)nc2n(C2CCCC2)c1=O
InChIKey: SGJLSPUSUBJWHO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin)
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 446.56, ALogP 4.02, HBA 8, HBD 2, PSA 101.8, QED 0.57
Compound (SMILES): CCc1cc(O)ccc1-c1ccc2c(-c3nc4c([nH]3)C[C@@H](C(=O)N3CC(N(C)C)C3)N(C(C)C)C4)n[nH]c2c1
InChIKey: VQIIUJSNIKEMCK-MHZLTWQESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Biochemical Kinase Assay: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies.Serially diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for 1 h. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for 1 h before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.
Measurement: Ki = 0.063 nM (pChEMBL 10.199999809265137)
Descriptors: MW 527.67, ALogP 3.8, HBA 6, HBD 3, PSA 104.38, QED 0.35
Compound (SMILES): COc1cccc2[nH]c(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]3CCNC3=O)C(=O)COP(=O)(O)O)cc12
InChIKey: FQKALOFOWPDTED-WBAXXEDZSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Binding affinity of SARS-Cov-2 M pro expressed in Escherichia coli cells BL21(DE3) assessed as inhibition constant preincubated for 30 mins followed by substrate addition of DABCYL-KTSAVLQSGFRKM-EDANS (aBachem) measured after 15 mins
Measurement: Ki = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 552.52, ALogP 1.01, HBA 7, HBD 6, PSA 196.15, QED 0.2
Compound (SMILES): CC(C)(C)[C@H](NC(=O)c1ccc(N)c(Cl)c1)C(=O)N1CCC[C@H]1C(=O)N[C@H](C=O)CC(=O)O
InChIKey: SOZONDBMOYWSRW-QANKJYHBSA-N
Target: Caspase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29466
Assay: Inhibition of caspase 1 (unknown origin)
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 480.95, ALogP 1.22, HBA 6, HBD 4, PSA 158.9, QED 0.32
Compound (SMILES): COC[C@H]1CN(C(=O)[C@]2(F)CN(C3CCCC3)C[C@H]2c2ccc(OC)cc2)C[C@@H]1c1ccc(C(F)(F)F)cc1N1CCC(C(=O)O)CC1.O=P(O)(O)O
InChIKey: PICGAOGKGDTMCU-ZPNFXMDPSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Agonist activity at human MC1R expressed in HEK293 cells assessed as alpha-MSH-induced cAMP production incubated for 30 mins by fluorescence based assay
Measurement: EC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 675.76, ALogP 5.95, HBA 6, HBD 1, PSA 82.55, QED 0.33
Compound (SMILES): O=C1Nc2ccc(OC(F)(F)F)cc2/C1=C1/Nc2ccccc2/C1=N\OCCN1CCNCC1
InChIKey: FNYRHYHVDYNRKI-DHEGUPKZSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: In Vitro Kinase Assay: The inhibition of the FLT3 kinase activity was measured with homogeneous, time-resolved fluorescence (HTRF) assays. Recombinant proteins containing the FLT3 kinase domain were purchased from Invitrogen (Carlsbad, Calif., USA). Optimal enzyme, ATP, and substrate concentrations were established with the HTRF KinEASE kit (Cisbio, France) according to the manufacturer's instructions. The FLT3 enzymes were mixed with serially diluted compounds and peptide substrates in a kinase reaction buffer (50 mM HEPES (pH 7.0), 500 μM ATP, 0.1 mM sodium orthovanadate, 5 mM MgCl2, 1 mM DTT, 0.01% bovine serum albumin (BSA), and 0.02% NaN3). Ten microliters of the total volume of the kinase reaction were added to the wells of a 96-well assay plate. The kinase reactions were incubated for 30 min at 25° C. For the detection of the phospho-substrate, the Eu3b-Cryptate-conjugated mouse monoclonal antibody (PT66) and the streptavidin-XL665 (SA-XL) were added, and the reactions were then incubated for 1 hour at 25° C. The signal was measured on an Victor X5 multi-label reader (PerkinElmer, Waltham, Mass., USA). The curve was fitted by nonlinear regression, and the IC50 was calculated using GraphPad Prism 5.01 (GraphPad, La Jolla, Calif., USA).
Measurement: IC50 = 40.2 nM (pChEMBL 7.400000095367432)
Descriptors: MW 473.46, ALogP 3, HBA 7, HBD 3, PSA 87.22, QED 0.35
Compound (SMILES): Clc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1
InChIKey: NZGFDKKHMVZHFL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 248 nM (pChEMBL 6.610000133514404)
Descriptors: MW 282.77, ALogP 4.06, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): Cc1cc(/C=C/c2cc3c4c(c2)CCCN4CCC3)cc(C)[n+]1CCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1
InChIKey: CXAKWVHJKJFJLW-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cells
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 860.14, ALogP 8.22, HBA 7, HBD 2, PSA 106.69, QED 0.08
Compound (SMILES): O=C(CCCCCNC(=O)COc1ccc(/C=C/C2=[N+]3C(=Cc4ccc(-c5cccs5)n4[B-]3(F)F)C=C2)cc1)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1
InChIKey: PHRZGNXUUFTVSE-RELWKKBWSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cells
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 1117.15
Compound (SMILES): CNC(=O)[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: XBAKNTZJMPFBQQ-SLYNCCJLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 555.49, ALogP 5.5, HBA 3, HBD 1, PSA 63.24, QED 0.4
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)c1ccco1
InChIKey: DHIWGBBDYYOLLT-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS and nigericin-stimulated human PBMC cells assessed as reduction in IL-1beta release preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with nigericin for 1.5 hrs by ELISA analysis
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 346.41, ALogP 2.77, HBA 4, HBD 2, PSA 88.41, QED 0.89
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccccc3)c3cccc(O)c3)cc2)CC1
InChIKey: ANMDBOUDORUSLO-NVQSTNCTSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 455.64, ALogP 6.71, HBA 3, HBD 2, PSA 43.7, QED 0.37
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCC[C@@H]2CO)cc1)c1ccccc1
InChIKey: QMJDQQMIKSBOSP-FYUFQVDVSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 473.61, ALogP 4.96, HBA 5, HBD 3, PSA 73.16, QED 0.34
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CCNCC2)cc1)c1ccccc1
InChIKey: SYZJGNRKRGPMOF-BYYHNAKLSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: In an ERR alpha binding assay, GST-bound ERR alpha LBD was used, and all experiments other than that was the same as the ERR gamma binding assay.In an ERR beta binding assay, GST-bound ERR alpha LBD was used so that a final concentration was 10 nM and a fluorescein-conjugated coactivator PGC1a was 250 nM, and all experiments other than that was the same as the ERR gamma binding assay.In an ER alpha binding assay, a GST-bound ER alpha ligand-binding domain (LBD) was added to a 384 well plate to which the arylethene derivative of the present invention was added to a final concentration of 7.3 nM. Then, a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 250 nM and 5 nM, respectively, and beta-estradiol as an agonist was added to a final concentration of 4 nM. All subsequent experiments was the same as the ERR gamma binding assay.
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 413.56, ALogP 5.59, HBA 3, HBD 3, PSA 52.49, QED 0.44
Compound (SMILES): CCOC[C@@H](NC(=N)NC(=O)Cc1ccc(OC)c(OC)c1)C(=O)Nc1cc(S(N)(=O)=O)ccc1C
InChIKey: SVYKWSMAQYLXOQ-GOSISDBHSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of recombinant human liver Cathepsin D using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 521.6, ALogP 0.89, HBA 8, HBD 5, PSA 181.93, QED 0.21
Compound (SMILES): CN1CCC[C@@H]1CCOc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1
InChIKey: ZUSXRJKXJTTXKD-FYUFQVDVSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: In an ERR alpha binding assay, GST-bound ERR alpha LBD was used, and all experiments other than that was the same as the ERR gamma binding assay.In an ERR beta binding assay, GST-bound ERR alpha LBD was used so that a final concentration was 10 nM and a fluorescein-conjugated coactivator PGC1a was 250 nM, and all experiments other than that was the same as the ERR gamma binding assay.In an ER alpha binding assay, a GST-bound ER alpha ligand-binding domain (LBD) was added to a 384 well plate to which the arylethene derivative of the present invention was added to a final concentration of 7.3 nM. Then, a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 250 nM and 5 nM, respectively, and beta-estradiol as an agonist was added to a final concentration of 4 nM. All subsequent experiments was the same as the ERR gamma binding assay.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 457.61, ALogP 5.99, HBA 4, HBD 2, PSA 52.93, QED 0.37
Compound (SMILES): Cc1cc(/C=C/c2cc3c4c(c2)CCCN4CCC3)cc(C)[n+]1CCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1
InChIKey: MMTRDAGHFRJWIB-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cells
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 807.12, ALogP 7.89, HBA 6, HBD 1, PSA 66.25, QED 0.12
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CC2)cc1)c1ccccc1
InChIKey: QVQADUPEEMYSFQ-RQZHXJHFSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 415.53, ALogP 4.82, HBA 4, HBD 2, PSA 52.7, QED 0.37
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3CCCCC3C(=O)NCCN)cc2Cl)cccc1-c1ccccc1
InChIKey: MUNAGIHEZQSSOB-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of interaction of PD-1 (unknown origin) expressed in Jurkat T cells carrying luciferase reporter under the control of NFAT promoter/PD-L1 (unknown origin) expressed in CHO cells co-expressing TCR ligand and T-cell surrogate pretreated with CHO cells for 0.5 hrs followed by Jurkat T cell addition and measured after 5 hrs by luminescence based analysis
Measurement: EC50 = 4650 nM (pChEMBL 5.329999923706055)
Descriptors: MW 623.2, ALogP 6.77, HBA 6, HBD 2, PSA 100.61, QED 0.18
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(O)cc3)cc2)CC1
InChIKey: WFBBMXRSHREWDN-NVQSTNCTSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 455.64, ALogP 6.71, HBA 3, HBD 2, PSA 43.7, QED 0.37
Compound (SMILES): CN1C(=O)C(F)(F)C[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: UENBCEQAMCZVQL-MIZPHKNDSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: General RORgamma 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). 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 rt 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. The IC50 value is defined as the concentration of test compound needed to reduce [3H] 25-hydroxycholesterol specific binding by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 660.53, ALogP 5.2, HBA 4, HBD 0, PSA 74.76, QED 0.33
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1
InChIKey: BDWDGROOZISTTC-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cells
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 834.1, ALogP 8.14, HBA 7, HBD 2, PSA 106.69, QED 0.06
Compound (SMILES): Cc1cccc(C2NCCc3c2[nH]c2ccc(Cl)cc32)c1
InChIKey: LFDABBDWOQSOAF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 481 nM (pChEMBL 6.320000171661377)
Descriptors: MW 296.8, ALogP 4.36, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(C(=O)NCCN4CCN(CCCCC5CCN(CC(=O)N6c7ccccc7NC(=O)c7ccccc76)CC5)CC4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: XJFLDBYRKJAMIK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cells
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 931.15, ALogP 5.83, HBA 10, HBD 2, PSA 147.75, QED 0.08
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCCC2)cc1)c1ccccc1
InChIKey: SDVZGUZPOXADLQ-ZIADKAODSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 443.59, ALogP 5.6, HBA 4, HBD 2, PSA 52.93, QED 0.4
Compound (SMILES): CN1CCCC1CCOc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1
InChIKey: ZUSXRJKXJTTXKD-FLWNBWAVSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 457.61, ALogP 5.99, HBA 4, HBD 2, PSA 52.93, QED 0.37
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCCCC2)cc1)c1ccccc1
InChIKey: UFPFMVPHDSUBQY-FLWNBWAVSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 457.61, ALogP 5.99, HBA 4, HBD 2, PSA 52.93, QED 0.37
Compound (SMILES): O=c1c2cccn2c2ccccc2n1CCCN1CCC(c2ccc(Cl)cc2)CC1
InChIKey: WOSMCMULWWHMIV-UHFFFAOYSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: GPCR PRESTO-Tango dose-response in antagonist mode with target: ADRA2A
Measurement: IC50 = 160.75 nM (pChEMBL 6.789999961853027)
Descriptors: MW 419.96, ALogP 5.18, HBA 4, HBD 0, PSA 29.65, QED 0.45
Compound (SMILES): NC(N)=NCCCOc1ccc(C(=O)Nc2ccccc2Oc2ccccc2)cc1
InChIKey: JDTMQBUKHRJGON-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human recombinant Cav3.2 alpha1 subunit expressed in HEK293T cells assessed as inhibition of calcium influx measured for 300 secs by FLIPR assay
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 404.47, ALogP 3.77, HBA 4, HBD 3, PSA 111.96, QED 0.29
Compound (SMILES): COC(=O)[C@@H](C)NC(=O)c1ccc(NC(=O)c2[nH]c(C)c(Cl)c2Cl)c(OC2CCNCC2)c1
InChIKey: XKRJEBDYVJJENF-GFCCVEGCSA-N
Target: DNA topoisomerase 2-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P11388
Assay: Inhibition of human DNA topoisomerase 2 alpha assessed as relaxation of supercoiled plasmid pNO1 DNA incubated for 30 mins by fluorescence based analysis
Measurement: IC50 = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 497.38, ALogP 3.3, HBA 6, HBD 4, PSA 121.55, QED 0.44
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CCN(C3CC3)CC2)cc1)c1ccccc1
InChIKey: QLPDYHPRQYYVTE-NVQSTNCTSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 453.63, ALogP 6.47, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): COC(=O)c1ccc(CN2CCC(O)(Cn3cnc4c(-c5ccc(CN)cc5)n(C)nc4c3=O)CC2)c(Cl)c1
InChIKey: AQZDRXXVFOYWHG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis
Measurement: IC50 = 60.7 nM (pChEMBL 7.21999979019165)
Descriptors: MW 551.05, ALogP 2.72, HBA 10, HBD 2, PSA 128.5, QED 0.34
Compound (SMILES): CN1CCN(CCO/N=C2C(=C3/C(=O)Nc4ccc(F)cc43)/Nc3ccccc3/2)CC1
InChIKey: KGKUYUPJWMDVRQ-DYGSTNMMSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: In Vitro Kinase Assay: The inhibition of the FLT3 kinase activity was measured with homogeneous, time-resolved fluorescence (HTRF) assays. Recombinant proteins containing the FLT3 kinase domain were purchased from Invitrogen (Carlsbad, Calif., USA). Optimal enzyme, ATP, and substrate concentrations were established with the HTRF KinEASE kit (Cisbio, France) according to the manufacturer's instructions. The FLT3 enzymes were mixed with serially diluted compounds and peptide substrates in a kinase reaction buffer (50 mM HEPES (pH 7.0), 500 μM ATP, 0.1 mM sodium orthovanadate, 5 mM MgCl2, 1 mM DTT, 0.01% bovine serum albumin (BSA), and 0.02% NaN3). Ten microliters of the total volume of the kinase reaction were added to the wells of a 96-well assay plate. The kinase reactions were incubated for 30 min at 25° C. For the detection of the phospho-substrate, the Eu3b-Cryptate-conjugated mouse monoclonal antibody (PT66) and the streptavidin-XL665 (SA-XL) were added, and the reactions were then incubated for 1 hour at 25° C. The signal was measured on an Victor X5 multi-label reader (PerkinElmer, Waltham, Mass., USA). The curve was fitted by nonlinear regression, and the IC50 was calculated using GraphPad Prism 5.01 (GraphPad, La Jolla, Calif., USA).
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 421.48, ALogP 2.58, HBA 6, HBD 2, PSA 69.2, QED 0.45
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCC3(CCCC3)C2)cc1)c1ccccc1
InChIKey: FACDVWBDBZWZTA-MVJHLKBCSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: ERRγ: The arylethene derivative of the present invention was sequentially added to a 384 well plate from a concentration of 10 μM to a final concentration of two-fold dilution. Then, a GST-bound ERR gamma ligand-binding domain (LBD) was added to a final concentration of 5 nM, and a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 500 nM and 5 nM, respectively. After all reagents were added, a reaction was carried out with gentle shaking at 20° C. for 1 hour, and after the reaction, a binding activity was measured by a TR-FRET method. That is, excitation at 340 nm was performed, each emission value at 495 nm and 520 nm was measured, the result assay was a value measured at 490 nm/a value measured at 520 nm, and an analysis program was Prism 6.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 497.68, ALogP 6.77, HBA 4, HBD 2, PSA 52.93, QED 0.3
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2C[C@H]3C[C@H]3[C@H]2CO)cc1)c1ccccc1
InChIKey: UTNLGSPOQMFYKD-UBOZUKHVSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding Assay: In an ERR alpha binding assay, GST-bound ERR alpha LBD was used, and all experiments other than that was the same as the ERR gamma binding assay.In an ERR beta binding assay, GST-bound ERR alpha LBD was used so that a final concentration was 10 nM and a fluorescein-conjugated coactivator PGC1a was 250 nM, and all experiments other than that was the same as the ERR gamma binding assay.In an ER alpha binding assay, a GST-bound ER alpha ligand-binding domain (LBD) was added to a 384 well plate to which the arylethene derivative of the present invention was added to a final concentration of 7.3 nM. Then, a fluorescein-conjugated coactivator PGC1a and a Tb-a-GST antibody were added to 250 nM and 5 nM, respectively, and beta-estradiol as an agonist was added to a final concentration of 4 nM. All subsequent experiments was the same as the ERR gamma binding assay.
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 485.62, ALogP 4.82, HBA 5, HBD 3, PSA 73.16, QED 0.34
Compound (SMILES): O=C1Nc2ccc([N+](=O)[O-])cc2/C1=C1/Nc2ccccc2/C1=N\OCCN1CCNCC1
InChIKey: YJZHKGCIOGFCIX-OQBIKMBDSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: In Vitro Kinase Assay: The inhibition of the FLT3 kinase activity was measured with homogeneous, time-resolved fluorescence (HTRF) assays. Recombinant proteins containing the FLT3 kinase domain were purchased from Invitrogen (Carlsbad, Calif., USA). Optimal enzyme, ATP, and substrate concentrations were established with the HTRF KinEASE kit (Cisbio, France) according to the manufacturer's instructions. The FLT3 enzymes were mixed with serially diluted compounds and peptide substrates in a kinase reaction buffer (50 mM HEPES (pH 7.0), 500 μM ATP, 0.1 mM sodium orthovanadate, 5 mM MgCl2, 1 mM DTT, 0.01% bovine serum albumin (BSA), and 0.02% NaN3). Ten microliters of the total volume of the kinase reaction were added to the wells of a 96-well assay plate. The kinase reactions were incubated for 30 min at 25° C. For the detection of the phospho-substrate, the Eu3b-Cryptate-conjugated mouse monoclonal antibody (PT66) and the streptavidin-XL665 (SA-XL) were added, and the reactions were then incubated for 1 hour at 25° C. The signal was measured on an Victor X5 multi-label reader (PerkinElmer, Waltham, Mass., USA). The curve was fitted by nonlinear regression, and the IC50 was calculated using GraphPad Prism 5.01 (GraphPad, La Jolla, Calif., USA).
Measurement: IC50 = 13.2 nM (pChEMBL 7.880000114440918)
Descriptors: MW 434.46, ALogP 2.01, HBA 8, HBD 3, PSA 121.13, QED 0.28
Compound (SMILES): CN(C)C(=O)[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: PLVOSTSJRBASBA-KAGYGMCKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 569.51, ALogP 5.84, HBA 3, HBD 0, PSA 54.45, QED 0.34
Compound (SMILES): O=C1Nc2ccccc2/C1=C1/Nc2ccccc2/C1=N\OCCN1CCNCC1
InChIKey: ULNQWYGVWVDLPK-OQBIKMBDSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: In Vitro Kinase Assay: The inhibition of the FLT3 kinase activity was measured with homogeneous, time-resolved fluorescence (HTRF) assays. Recombinant proteins containing the FLT3 kinase domain were purchased from Invitrogen (Carlsbad, Calif., USA). Optimal enzyme, ATP, and substrate concentrations were established with the HTRF KinEASE kit (Cisbio, France) according to the manufacturer's instructions. The FLT3 enzymes were mixed with serially diluted compounds and peptide substrates in a kinase reaction buffer (50 mM HEPES (pH 7.0), 500 μM ATP, 0.1 mM sodium orthovanadate, 5 mM MgCl2, 1 mM DTT, 0.01% bovine serum albumin (BSA), and 0.02% NaN3). Ten microliters of the total volume of the kinase reaction were added to the wells of a 96-well assay plate. The kinase reactions were incubated for 30 min at 25° C. For the detection of the phospho-substrate, the Eu3b-Cryptate-conjugated mouse monoclonal antibody (PT66) and the streptavidin-XL665 (SA-XL) were added, and the reactions were then incubated for 1 hour at 25° C. The signal was measured on an Victor X5 multi-label reader (PerkinElmer, Waltham, Mass., USA). The curve was fitted by nonlinear regression, and the IC50 was calculated using GraphPad Prism 5.01 (GraphPad, La Jolla, Calif., USA).
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 389.46, ALogP 2.1, HBA 6, HBD 3, PSA 77.99, QED 0.42