lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1OCCNCC1(F)CCN(C(=O)c2ccc(Cl)c(Cl)c2)CC1
InChIKey: WWQYGUPGPQFXAD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Radioligand Binding Assay: D2 Dopamine Receptor:Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human D2 receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-methylspiperon (final concentration 0.4 nM, Kd 0.4 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM HEPES, pH 7.4, 50 mM NaCl, 5 mM MgCl2, 0.5 mM EDTA) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). (+)-butaclamol (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 37° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 455.36, ALogP 4.61, HBA 4, HBD 1, PSA 50.8, QED 0.59
Compound (SMILES): C[C@]1(c2cc(/C=C(\F)c3cnc(C#N)cn3)ccc2F)N=C(N)S[C@@]2(C(=O)N3CCOCC3)C[C@H]21
InChIKey: KSLJUUCKMWVFIH-AWTRGSECSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human HEK293 cells transfected with human wild type APP assessed as reduction in Abeta40 production incubated for overnight by ELISA
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 496.54, ALogP 2.85, HBA 8, HBD 1, PSA 117.49, QED 0.69
Compound (SMILES): CC(C)(O)CCc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: NHIOUCSDAKKLBQ-HNNXBMFYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 447.51, ALogP 4.51, HBA 5, HBD 4, PSA 85.86, QED 0.45
Compound (SMILES): C[C@H]1CCNC[C@@H]1Nc1ncc(C(F)(F)F)c(-c2c[nH]c3ccccc23)n1
InChIKey: YGVSSBPHNLLAHU-ZBEGNZNMSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 375.4, ALogP 4.05, HBA 4, HBD 3, PSA 65.63, QED 0.65
Compound (SMILES): Nc1nc(Cl)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(C(=O)NCCCF)C[C@H]12
InChIKey: XTFAHNFBCMTXMV-RFXZSQAESA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 384.8, ALogP -0.18, HBA 8, HBD 4, PSA 139.18, QED 0.41
Compound (SMILES): O=S(=O)(Oc1ccccc1)C1CC2OC1C(c1ccc(O)cc1)=C2c1ccc(O)cc1
InChIKey: KRJVPVGVFUQQGQ-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at ERbeta (unknown origin) expressed in human HEK293T cells assessed as inhibition of 17beta-estradiol-induced transcriptional activities by measuring ERE driven reporter gene expression measured after 24 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 633 nM (pChEMBL 6.199999809265137)
Descriptors: MW 436.49, ALogP 3.96, HBA 6, HBD 2, PSA 93.06, QED 0.59
Compound (SMILES): CCOc1ccc2occc2c1[C@@H]1C[C@H]1CN.Cl
InChIKey: GHJYHQVUKYWAKG-QLSWKGBWSA-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 = 585 nM (pChEMBL 6.230000019073486)
Descriptors: MW 231.29, ALogP 2.89, HBA 3, HBD 1, PSA 48.39, QED 0.88
Compound (SMILES): c1ccc(Oc2ccc(OCCCN3CCN(c4ccncc4)CC3)cc2)cc1
InChIKey: GCXYUJQPRFLTRZ-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]histamine from Gialpha2/Gbeta1gamma2-coupled human H4R expressed in Sf9 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 389.5, ALogP 4.47, HBA 5, HBD 0, PSA 37.83, QED 0.53
Compound (SMILES): COc1cc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)ccc1NC(=O)/C=C/CN(C)C
InChIKey: DLVVFKMWFVZWDD-AQDCRGGLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 474.57, ALogP 3.02, HBA 7, HBD 2, PSA 99.69, QED 0.48
Compound (SMILES): CN(C)C(=O)c1sc2nc(N3CCC(S(C)(=O)=O)CC3)cc(C(F)(F)F)c2c1N
InChIKey: HHYGVXHXNNIDJF-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 7244.36 nM (pChEMBL 5.139999866485596)
Descriptors: MW 450.51, ALogP 2.61, HBA 7, HBD 1, PSA 96.6, QED 0.77
Compound (SMILES): CC(=O)Nc1ncc(CN2CCC[C@H](Cc3cc(C)nc(C)c3)C2)s1
InChIKey: CYFBRQHYEQKYHH-MRXNPFEDSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Cell-based OGA assay
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 358.51, ALogP 3.57, HBA 5, HBD 1, PSA 58.12, QED 0.89
Compound (SMILES): O=C(c1cnc(NCc2cnccn2)nc1)N1CCC2(CCOCC2)C1
InChIKey: VGRLXWFIXGZRMS-UHFFFAOYSA-N
Target: Pantetheinase (SINGLE PROTEIN), Homo sapiens
UniProt: O95497
Assay: Binding affinity to human vanin-1 by surface plasmon resonance method
Measurement: Kd = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 354.41, ALogP 1.52, HBA 7, HBD 1, PSA 93.13, QED 0.89
Compound (SMILES): COc1nc2ccc([C@@](O)(c3ccccc3)C3CCN(C(C)=O)CC3)cc2c(Cl)c1Cc1ccc(-n2cccn2)cc1
InChIKey: QBIGUDRHHJTXKG-UUWRZZSWSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: LXRalpha In-house nuclear receptor screen
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 581.12, ALogP 6.17, HBA 6, HBD 1, PSA 80.48, QED 0.25
Compound (SMILES): CCOc1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C#Cc2cnc(C(=O)O)cc2OC)c2ncccc12
InChIKey: FNBUZGRPJLEIMO-UHFFFAOYSA-N
Target: Monocarboxylate transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53985
Assay: Lactate efflux inhibition assay (SNU-398)
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 537.98, ALogP 4.59, HBA 7, HBD 2, PSA 127.71, QED 0.33
Compound (SMILES): CC(=O)Nc1nc(CN2CCC[C@H](Cc3cc(C)nc(C)c3)C2)cs1
InChIKey: VKYYOTCDIVOPRO-MRXNPFEDSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 1348.96 nM (pChEMBL 5.869999885559082)
Descriptors: MW 358.51, ALogP 3.57, HBA 5, HBD 1, PSA 58.12, QED 0.89
Compound (SMILES): COc1cc(C(=O)O)ncc1C#Cc1ccccc1NS(=O)(=O)c1cccc2c(N(C)C)ccnc12
InChIKey: MMSNEMMBFRAGPO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: GPCRScan assay: inhibition of 5-HT6
Measurement: Ki = 1445.44 nM (pChEMBL 5.840000152587891)
Descriptors: MW 502.55, ALogP 3.6, HBA 7, HBD 2, PSA 121.72, QED 0.38
Compound (SMILES): Cc1nc(NCc2cnccn2)ncc1C(=O)N1CCC2(CCOCC2)C1
InChIKey: ZNKDYARBMJGNQA-UHFFFAOYSA-N
Target: Pantetheinase (SINGLE PROTEIN), Homo sapiens
UniProt: O95497
Assay: Human plasma vanin-1 assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 368.44, ALogP 1.83, HBA 7, HBD 1, PSA 93.13, QED 0.88
Compound (SMILES): N#CN1CC[C@H](C(=O)Nc2nc3c(s2)CN(C(=O)CN=[N+]=[N-])CC3)C1
InChIKey: KIWKRCCIHSGWQS-VIFPVBQESA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: GPCRScan assay: inhibition of Sigma 1
Measurement: Ki = 3388.44 nM (pChEMBL 5.46999979019165)
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-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Affinity Phenotypic Cellular interaction: (CellTiter-Glo luminescent cell viability assay (ZR-75-1, breast cancer cells)) EUB0001563a AKT2
Measurement: EC50 = 4200 nM (pChEMBL 5.380000114440918)
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: Parkinson disease protein 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99497
Assay: Inhibition of N-terminal GST-tagged human recombinant PARK7 expressed in Escherichia coli BL21(DE3)Rosetta2 cells assessed as reduction in JQ-107-labelled PARK7 band intensity incubated for 1 hr followed by incubation with JQ-107 and measured for 2 hrs by fluorescence polarization assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 360.4, ALogP 1.08, HBA 7, HBD 1, PSA 138.09, QED 0.37
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 eGFP fused SARS-CoV2 main protease transfected in HEK293T/17 cells incubated for 72 hrs by fluorescence based flow cytometry analysis
Measurement: EC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 499.53, ALogP 1.1, HBA 5, HBD 3, PSA 131.4, QED 0.5
Compound (SMILES): Nc1nnc(CN[C@@H]2C[C@H]2c2ccc(OCc3ccccc3)cc2)o1
InChIKey: XBBRLCXCBCZIOI-DLBZAZTESA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of MAO-B (unknown origin)
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 336.4, ALogP 2.88, HBA 6, HBD 2, PSA 86.2, QED 0.69
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: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
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: IC50 = 2.51 nM (pChEMBL 8.600000381469727)
Descriptors: MW 527.67, ALogP 3.8, HBA 6, HBD 3, PSA 104.38, QED 0.35
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: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Binding affinity to human MC4R assessed as inhibition constant
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 675.76, ALogP 5.95, HBA 6, HBD 1, PSA 82.55, QED 0.33
Compound (SMILES): Clc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1
InChIKey: NZGFDKKHMVZHFL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C 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 = 69.18 nM (pChEMBL 7.159999847412109)
Descriptors: MW 282.77, ALogP 4.06, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccccc3)c3cccc(O)c3)cc2)CC1
InChIKey: ANMDBOUDORUSLO-NVQSTNCTSA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
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 = 7818 nM (pChEMBL 5.110000133514404)
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: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
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 > 10000 nM (pChEMBL 5)
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 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
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 = 992 nM (pChEMBL 6)
Descriptors: MW 413.56, ALogP 5.59, HBA 3, HBD 3, PSA 52.49, QED 0.44
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 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 455.64, ALogP 6.71, HBA 3, HBD 2, PSA 43.7, QED 0.37
Compound (SMILES): Cc1cccc(C2NCCc3c2[nH]c2ccc(Cl)cc32)c1
InChIKey: LFDABBDWOQSOAF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C 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 = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 296.8, ALogP 4.36, HBA 1, HBD 2, PSA 27.82, QED 0.69
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 = 34 nM (pChEMBL 7.46999979019165)
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(C2CCN(C3CC3)CC2)cc1)c1ccccc1
InChIKey: QLPDYHPRQYYVTE-NVQSTNCTSA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
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 = 1665 nM (pChEMBL 5.78000020980835)
Descriptors: MW 453.63, ALogP 6.47, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCC3(CCCC3)C2)cc1)c1ccccc1
InChIKey: FACDVWBDBZWZTA-MVJHLKBCSA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
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 = 3070 nM (pChEMBL 5.510000228881836)
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 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
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 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 485.62, ALogP 4.82, HBA 5, HBD 3, PSA 73.16, QED 0.34
Compound (SMILES): CN1C(=O)[C@@H](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: PDJZLHFYLDTXLV-VMIIQTFKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: 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.
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 642.54, ALogP 4.9, HBA 4, HBD 0, PSA 74.76, QED 0.35
Compound (SMILES): FC(F)(F)c1cnc(Nc2ccc3ncoc3c2)nc1NC1CC1
InChIKey: ZMGUVTBINPLWRA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: ULK1 inhibition assay: Gamma-32P assays to measure ULK1 kinase activity were performed as previously described. Briefly, Flag ULK1 was transfected into HEK293T cells and 20 hours later treated as indicated. The immmunoprecipitate was washed in IP buffer 3 times, and washed in kinase buffer (25 mM MOPS, pH 7.5, 1 mM EGTA, 0.1 mM Na3VO4, 15 mM MgCl2,). Hot and cold ATP were added at a 100 μM final concentration. As substrates, GST or the recombinant protein GST-Atg101 purified from E. coli were used at 1 μg for each reaction. Reactions were boiled, run out on SDS page gel. The gel was dried, and imaged using PhosphoImager software. For cold assays to asses ULK1, Flag ULK1 which was transiently overexpressed and immunoprecipited from HEK293T cells. Reactions were then run out on SDS page gel, transferred to PVDF membrane and blotted for total levelsFluorescence MicroscopyVps34flox/flox MEFs were reconstituted with Flag-VPS34 and either p40FX or GFP-DFCP1. 48 hours post infection with adenovirus expressing Cre recombinase (MOI of 100), cells were plated on glass coverslips at a density of 3×105 cells per well in 6-well tissue culture plates. 18 h later, cells were fixed in 4% PFA in PBS for 10 minutes and permeabilized in 0.2% Triton in PBS for 10 minutes. The following primary antibodies were used: mouse anti-Myc epitope and LC3B XP antibody (2276 and 3868 respectively, Cell Signaling Technologies). Secondary antibodies were anti-rabbit Alexa488 and anti-mouse Alexa594 (Molecular Probes, 1:1000. Cells were then fixed and counter stained with DAPI. Coverslips were mounted in FluoromountG (SouthernBiothech). Images were acquired on a Zeiss Axioplan2 epifluorescence microscope coupled to the Openlab software. Confocal images of mitotracker were taken on Zeiss LSM 710 laser scanning confocal microscope. 10 random fields per condition were acquired using the 100× objective and representative images shown. Glass coverslips were mounted directly on plate with FluoromountG and images taken on Zeiss Axioplan2 epifluorescence microscope.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 335.29, ALogP 3.95, HBA 6, HBD 2, PSA 75.87, QED 0.75
Compound (SMILES): C[C@H]1CCCN1Cc1nc2cc(NC(=O)c3ccc4cnccc4c3)ccc2[nH]1
InChIKey: ZRTFTZCKJUNZIU-HNNXBMFYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Selectivity interaction (Bromodomain panel (TR-FRET assay)) EUB0000283b CECR2
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 385.47, ALogP 4.35, HBA 4, HBD 2, PSA 73.91, QED 0.55
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(Cl)c2c(=O)n1-c1cncc(C#N)c1
InChIKey: RWAVWFHYGLYYJE-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as reduction in anti-FCepsilonR1 mAb-stimulated basophil activation preincubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation and measured after 25 mins by flow cytometry analysis
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 458.87, ALogP 2.3, HBA 11, HBD 3, PSA 185.21, QED 0.41
Compound (SMILES): COc1ccc(NC(=O)c2n[nH]c3ccc(-c4cncc(CN5CCCCC5)c4)cc23)cn1
InChIKey: YDPWZFPXWFTXNT-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 = 32 nM (pChEMBL 7.5)
Descriptors: MW 442.52, ALogP 4.27, HBA 6, HBD 2, PSA 96.03, QED 0.46
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1ccccc1S(C)(=O)=O
InChIKey: VRGGDBXPXSTVMJ-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 451.49, ALogP 2.99, HBA 9, HBD 2, PSA 139.58, QED 0.47
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: HZZNUWNFLHMBRW-AWEZNQCLSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 923 nM (pChEMBL 6.039999961853027)
Descriptors: MW 321.43, ALogP 3.35, HBA 4, HBD 3, PSA 65.63, QED 0.69
Compound (SMILES): O=C(Nc1ccc(-n2ccnc2)cc1)C(c1ccccc1)S(=O)(=O)O
InChIKey: UENXDQPHRHGNCL-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of His-tagged SHP1 (unknown origin) expressed in Escherichia coli BL21 cells using para-nitrophenyl phosphate as substrate incubated for 5 to 10 mins by microplate reader based spectrophotometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 357.39, ALogP 2.44, HBA 5, HBD 2, PSA 101.29, QED 0.68
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)cn2)CC1
InChIKey: XXRVQNFPJLDWCL-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta 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). 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%)))].
Measurement: EC50 = 479 nM (pChEMBL 6.320000171661377)
Descriptors: MW 427.51, ALogP 3.03, HBA 7, HBD 1, PSA 79.18, QED 0.54
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-DUSBFPBJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 1117.33
Compound (SMILES): COC(=O)Nc1cc(C(F)(F)F)c(-c2nc(N3CCOCC3)c3cc(CN4CCN(S(C)(=O)=O)CC4)cn3n2)cn1
InChIKey: KTLQDDGRBDLKMN-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3K p110delta/p85alpha using PIP2 as substrate in presence of ATP measured after 40 mins by HTRF assay
Measurement: IC50 = 78.7 nM (pChEMBL 7.099999904632568)
Descriptors: MW 598.61, ALogP 1.9, HBA 11, HBD 1, PSA 134.5, QED 0.45
Compound (SMILES): Nc1nc(-n2cc(C(=O)O)c(=O)c3cc(F)c([C@H]4C[C@@H](O)C4)c(Cl)c32)c(F)cc1F
InChIKey: PJIUHKYBPMWXEK-KNVOCYPGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 24800 nM (pChEMBL 4.610000133514404)
Descriptors: MW 439.78, ALogP 2.98, HBA 6, HBD 3, PSA 118.44, QED 0.58
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccc(Cl)cc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: HVLGSWMYZPWZTD-XOJVSUSESA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 0.6918 nM (pChEMBL 9.15999984741211)
Descriptors: MW 1108.7
Compound (SMILES): O=C(O)C[C@H](C(=O)N1CC[C@@H](CCc2ccc3c(n2)NCCC3)C1)c1ccccc1
InChIKey: FRVXYRMGRBRKHN-UTKZUKDTSA-N
Target: Integrin alpha-V/beta-8 (PROTEIN COMPLEX), Homo sapiens
UniProt: P26012
Assay: Inhibition of integrin alphavbeta8 (unknown origin) by fluorescence polarization assay
Measurement: IC50 > 79432.82 nM (pChEMBL 4.099999904632568)
Descriptors: MW 407.51, ALogP 3.48, HBA 4, HBD 2, PSA 82.53, QED 0.73
Compound (SMILES): Cc1ncc(C(=O)Nc2cc3cc(-c4cnc(C)n4C)ccc3cn2)s1
InChIKey: VKJVGBGYCJZKLW-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 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 363.45, ALogP 3.96, HBA 6, HBD 1, PSA 72.7, QED 0.6
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N(CC)Cc2ccccc2)cc1OC
InChIKey: OONJTMHYAWPQHW-FYWRMAATSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate after 15 mins by Ellman's method
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 396.49, ALogP 4.21, HBA 4, HBD 0, PSA 59.08, QED 0.63
Compound (SMILES): COc1cc(C(=O)N2CCCC(c3ccnc4ncnn34)C2)cc(OC)c1OC
InChIKey: QRHYHQMFAMRYKQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Inhibition of 6xHis-tagged rat recombinant PDE10A2 expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 551 nM (pChEMBL 6.260000228881836)
Descriptors: MW 397.44, ALogP 2.17, HBA 8, HBD 0, PSA 91.08, QED 0.65
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(C#CC#Cc2ccc(-c3cnc([C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)cc2)[nH]1)c1ccccc1.Cl.Cl
InChIKey: FFQVKTCXABDWBR-RYYFUXLTSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1b NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by Celltiter Glo assay
Measurement: IC50 = 0.012 nM (pChEMBL 10.920000076293945)
Descriptors: MW 744.85, ALogP 5.01, HBA 8, HBD 4, PSA 174.64, QED 0.17
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: IHOAWPUMJLGVEZ-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 448.53, ALogP 3.05, HBA 7, HBD 2, PSA 109.22, QED 0.6
Compound (SMILES): CC(C)(O)CC(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)nc3CC[C@@H]12
InChIKey: BGPNNQWYDHRLHD-QUZZAMIASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 614.56, ALogP 5.18, HBA 5, HBD 2, PSA 96.36, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: UWNAMJVFMQXNFA-IIWMTREJSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Agonist activity at human NPY2R expressed in CHO cells assessed as inhibition of forskolin-induced intracellular cAMP accumulation incubated for 30 mins in absence of 10% FBS by HTRF assay
Measurement: EC50 = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 4220.69
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cc[nH]n4)nc23)cc1
InChIKey: SDFNLJHDZXQOCL-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 317.39, ALogP 5.18, HBA 3, HBD 1, PSA 54.71, QED 0.55
Compound (SMILES): O=C(NO)c1ccc(CN(Cc2nnnn2Cc2ccccc2)C(=O)c2ccccc2C(F)(F)F)cc1
InChIKey: MEWDNULKAXEKII-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human recombinant HDAC4 using Boc-Lys-(epsilon-Tfa)-AMC fluorogenic substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 55400 nM (pChEMBL 4.260000228881836)
Descriptors: MW 510.48, ALogP 3.7, HBA 7, HBD 2, PSA 113.24, QED 0.28
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccn4)CC3)cc2C1=O
InChIKey: JLHMEGWPLLZUIA-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 380.49, ALogP 2.3, HBA 5, HBD 0, PSA 48.91, QED 0.72
Compound (SMILES): CC1CCCCN1CC(=O)n1c2ccccc2c2ccccc21
InChIKey: LWLHEWKCUGKMBK-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 = 52480.75 nM (pChEMBL 4.28000020980835)
Descriptors: MW 306.41, ALogP 4.31, HBA 3, HBD 0, PSA 25.24, QED 0.7
Compound (SMILES): O=C(NO)[C@H]1C[C@H](NS(=O)(=O)c2ccc(-c3ccccc3)cc2)CN1S(=O)(=O)c1ccc([N+](=O)[O-])cc1
InChIKey: YOSFZMCQPIHTKQ-PGRDOPGGSA-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 = 23280 nM (pChEMBL 4.630000114440918)
Descriptors: MW 546.58, ALogP 1.88, HBA 8, HBD 3, PSA 176.02, QED 0.22
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(C(C)C)c3ccccc34)cc2)cc1
InChIKey: DQWYVKIYWPYHFR-PMERELPUSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 536.72, ALogP 6.61, HBA 4, HBD 1, PSA 53.01, QED 0.31
Compound (SMILES): O=S(=O)(Oc1ccccc1)C1CC2OC1C(c1ccc(O)cc1)=C2c1ccc(O)cc1
InChIKey: KRJVPVGVFUQQGQ-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) assessed as inhibition constant
Measurement: Ki = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 436.49, ALogP 3.96, HBA 6, HBD 2, PSA 93.06, QED 0.59
Compound (SMILES): CN(C)C(=O)c1sc2nc(N3CCC(S(C)(=O)=O)CC3)cc(C(F)(F)F)c2c1N
InChIKey: HHYGVXHXNNIDJF-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Biochemical assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 450.51, ALogP 2.61, HBA 7, HBD 1, PSA 96.6, QED 0.77
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(N2C[C@H]3C[C@@H]2CN3c2cccnn2)s1
InChIKey: DLNFTRSEHUWEGO-HUUCEWRRSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: GPCRScan assay: inhibition of 5-HT1D
Measurement: Ki = 6453.57 nM (pChEMBL 5.190000057220459)
Descriptors: MW 393.48, ALogP 1.98, HBA 8, HBD 1, PSA 87.14, QED 0.71
Compound (SMILES): O=C(c1cnc(NCc2cnccn2)nc1)N1CCC2(CCOCC2)C1
InChIKey: VGRLXWFIXGZRMS-UHFFFAOYSA-N
Target: Pantetheinase (SINGLE PROTEIN), Homo sapiens
UniProt: O95497
Assay: Inhibition of vanin-1 in human HT-29 cells preincubated for 30 mins followed by chemiluminescent probe addition and measured after 5 mins by chemiluminescence imaging assay
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 354.41, ALogP 1.52, HBA 7, HBD 1, PSA 93.13, QED 0.89
Compound (SMILES): COc1nc2ccc([C@@](O)(c3ccccc3)C3CCN(C(C)=O)CC3)cc2c(Cl)c1Cc1ccc(-n2cccn2)cc1
InChIKey: QBIGUDRHHJTXKG-UUWRZZSWSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: LXRbeta In-house nuclear receptor screen
Measurement: IC50 ~ 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 581.12, ALogP 6.17, HBA 6, HBD 1, PSA 80.48, QED 0.25
Compound (SMILES): CCOc1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C#Cc2cnc(C(=O)O)cc2OC)c2ncccc12
InChIKey: FNBUZGRPJLEIMO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1E (SINGLE PROTEIN), Homo sapiens
UniProt: P28566
Assay: GPCRScan assay: inhibition of 5-HT1E
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 537.98, ALogP 4.59, HBA 7, HBD 2, PSA 127.71, QED 0.33
Compound (SMILES): CC(=O)Nc1nc(CN2CCC[C@H](Cc3cc(C)nc(C)c3)C2)cs1
InChIKey: VKYYOTCDIVOPRO-MRXNPFEDSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: GPCRScan assay: inhibition of DAT
Measurement: Ki = 5284.45 nM (pChEMBL 5.28000020980835)
Descriptors: MW 358.51, ALogP 3.57, HBA 5, HBD 1, PSA 58.12, QED 0.89
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(C)c3F)cc2)nc2cnccc12)C(=O)O
InChIKey: DVIVLYHDLNAXAT-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Quantification of produced ADP with 10 uM ATP
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 440.48, ALogP 5.56, HBA 5, HBD 2, PSA 98.9, QED 0.41
Compound (SMILES): COc1cc(C(=O)O)ncc1C#Cc1ccccc1NS(=O)(=O)c1cccc2c(N(C)C)ccnc12
InChIKey: MMSNEMMBFRAGPO-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: GPCRScan assay: inhibition of DAT
Measurement: Ki = 9585.29 nM (pChEMBL 5.019999980926514)
Descriptors: MW 502.55, ALogP 3.6, HBA 7, HBD 2, PSA 121.72, QED 0.38
Compound (SMILES): Cc1nc(NCc2cnccn2)ncc1C(=O)N1CCC2(CCOCC2)C1
InChIKey: ZNKDYARBMJGNQA-UHFFFAOYSA-N
Target: Pantetheinase (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0K8
Assay: Mouse plasma vanin-1 assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
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: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: GPCRScan assay: inhibition of 5-HT6
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 440.48, ALogP 5.56, HBA 5, HBD 2, PSA 98.9, QED 0.41
Compound (SMILES): N#CN1CC[C@H](C(=O)Nc2nc3c(s2)CN(C(=O)CN=[N+]=[N-])CC3)C1
InChIKey: KIWKRCCIHSGWQS-VIFPVBQESA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: NanoBRET (SGC Frankfurt) (MAPK14)
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 360.4, ALogP 1.08, HBA 7, HBD 1, PSA 138.09, QED 0.37