lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(Oc1cccc(Cl)c1)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: PIEDPXPDSBJFCQ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L receptor expressed in human HEK293 cells incubated for 1 hr by radioligand binding assay
Measurement: Ki = 566 nM (pChEMBL 6.25)
Descriptors: MW 348.84, ALogP 2, HBA 7, HBD 1, PSA 80.4, QED 0.9
Compound (SMILES): O=C(O)[C@H]1CCCN(c2nc(N3CCOCC3)nc(-n3c(C(F)F)nc4ccccc43)n2)C1
InChIKey: LZPFNUFLUGZHSO-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) expressed in baculovirus expression system by kinase-glo luminescence assay
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 459.46, ALogP 2.29, HBA 9, HBD 1, PSA 109.5, QED 0.61
Compound (SMILES): O=C1CCCN1c1ccc(C2CCN(CCc3cnn(-c4nccc5c(=O)[nH]cnc45)c3)CC2)cc1
InChIKey: OTYMAMBJVVRSCZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay
Measurement: IC50 = 188 nM (pChEMBL 6.730000019073486)
Descriptors: MW 483.58, ALogP 3.05, HBA 7, HBD 1, PSA 100.01, QED 0.45
Compound (SMILES): Cn1cc(NC(=O)c2ccc(NS(=O)(=O)c3ccccc3)cc2)cn1
InChIKey: XZNSLTQVQFNZRP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) incubated for 30 mins by enzyme immunoassay
Measurement: IC50 = 25180 nM (pChEMBL 4.599999904632568)
Descriptors: MW 356.41, ALogP 2.47, HBA 5, HBD 2, PSA 93.09, QED 0.73
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(S(=O)(=O)N2CCC(NC(=O)c3n[nH]cc3NC(=O)c3c(Cl)cccc3Cl)CC2)c1.O=C(O)C(F)(F)F
InChIKey: WFHAWMZQFFZNGT-OAZHBLANSA-N
Target: Cyclin-dependent kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: O94921
Assay: Inhibition of FLAG-tagged CDK14 (unknown origin) expressed in human HEK293 cells assessed as blocking of CDK14 pulldown incubated for 4 hrs by biotinylated JNK-IN- based pull down assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 648.57, ALogP 3.61, HBA 7, HBD 4, PSA 156.6, QED 0.24
Compound (SMILES): CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](n2cnc3c(N)ncnc32)C1(F)F)Oc1ccccc1
InChIKey: ZDCHYGVYUFSBFU-RUJHRXAISA-N
Target: NS5 (SINGLE PROTEIN), Zika virus
UniProt: A0A143MHK7
Assay: Inhibition of RNA-dependent RNA polymerase in ZIKV SL0612 infected in African green monkey Vero cells assessed as reduction in virus-induced cytopathic effect measured after 96 hrs post-infection by MTS assay
Measurement: EC50 = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 570.49, ALogP 2.07, HBA 12, HBD 4, PSA 183.94, QED 0.21
Compound (SMILES): Cc1nc2sc(C(=O)NC[C@H](C)c3cc(F)c(N4CC5CCC(C4)N5)cc3F)c(N)c2cc1F
InChIKey: MAHWCFFCPAXVDZ-XGNXJENSSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 489.57, ALogP 4.08, HBA 6, HBD 3, PSA 83.28, QED 0.5
Compound (SMILES): CN[C@@H]1CCCN(C(=O)c2nc(-c3ccc(C#N)c(F)c3)n(-c3ccc4nn(C)c(Cl)c4c3)c2C)C1
InChIKey: JAKGNRQBWOOXQA-GOSISDBHSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 in human THP1 cells assessed as induction of CD11b expression after 4 days by LIVE/DEAD violet staining based FACS analysis
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 505.99, ALogP 4.22, HBA 7, HBD 1, PSA 91.77, QED 0.45
Compound (SMILES): COc1cc(/C=C/C(=O)OCCCCCCCCN(C)CCOC(=O)c2cc(OC)c(OC)c(OC)c2)cc(OC)c1OC
InChIKey: XOVWMWDJBIAHEB-CCEZHUSRSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) in MDCK-MDR1 assessed as inhibtion of calcein-AM transport incubated for 30 mins by fluorescence assay
Measurement: EC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 617.74, ALogP 5.42, HBA 11, HBD 0, PSA 111.22, QED 0.1
Compound (SMILES): COc1cc(N(C)CCN(C)C)c(NC(=O)/C=C\C(C)C)cc1Nc1nc2c(c(-c3cn(C)c4ccccc34)n1)CSCC2
InChIKey: RDCUCIFMSZKXQC-SEYXRHQNSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/L858R double mutant (unknown origin) using biotin as substrate in presence of ATP by mobility shift assay based ELISA
Measurement: IC50 = 1621 nM (pChEMBL 5.789999961853027)
Descriptors: MW 613.83, ALogP 6.33, HBA 9, HBD 2, PSA 87.55, QED 0.19
Compound (SMILES): CCOCCc1cnc(NC(=O)NC)cc1Oc1cncc(C)c1
InChIKey: KKYXCDNGTUJMIB-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of human recombinant glucokinase using 5 mM glucose as substrate in presence of NAD+ and 4% HSA by glucose 6-phosphate dehydrogenase coupled assay
Measurement: EC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 330.39, ALogP 2.91, HBA 5, HBD 2, PSA 85.37, QED 0.76
Compound (SMILES): CC(=O)N1CCN(c2nccn3c(-c4ccc5c(c4)CC(=O)N5)c(-c4ccc(F)cc4)nc23)CC1
InChIKey: VIYLKXCSTCRPKT-UHFFFAOYSA-N
Target: GRIA1/CACNG2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y698
Assay: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay
Measurement: IC50 = 0.3981 nM (pChEMBL 9.399999618530273)
Descriptors: MW 470.51, ALogP 3.37, HBA 6, HBD 1, PSA 82.84, QED 0.5
Compound (SMILES): NC(=O)c1ccc(-c2cccnc2)cc1
InChIKey: HRWJRXNTRLZCAI-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of N-terminal GST-tagged MNK2 (unknown origin) (72 to 385 residues) expressed in Escherichia coli BL21 (DE3) cells using 5-FAM-TATKSGSTTKNRFVV-NH2 peptide as substrate preincubated with enzyme for 10 mins followed by substrate addition after 60 mins in presence of ATP by caliper mobility shift assay
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 198.22, ALogP 1.85, HBA 2, HBD 1, PSA 55.98, QED 0.8
Compound (SMILES): CN(C)C(=O)c1ccc(C2CN(C(=O)C[C@@H]3CCN(C#N)C3)C2)cc1
InChIKey: JUWHJTKPALEDBO-AWEZNQCLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). A Excitation 540 nm; A Emission 590 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 340.43, ALogP 1.51, HBA 4, HBD 0, PSA 67.65, QED 0.78
Compound (SMILES): CCCCNc1nc(N)nc(C)c1CCCCN.Cl.Cl
InChIKey: GREBOJNDVGSFRG-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 in human PBMC assessed as increase in TNF-alpha production after 16 hrs by immunoassay
Measurement: EC50 = 9260 nM (pChEMBL 5.03000020980835)
Descriptors: MW 251.38, ALogP 1.86, HBA 5, HBD 3, PSA 89.85, QED 0.61
Compound (SMILES): CCc1cc(-c2cnn(C)c2)cc(S(=O)(=O)c2cnc(CN)s2)c1.Cl
InChIKey: XAJYHKZTSFGXNC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAOA expressed in yeast incubated for 1 hr by luminescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 362.48, ALogP 2.4, HBA 7, HBD 1, PSA 90.87, QED 0.75
Compound (SMILES): Cc1c(N2CCN(Cc3cccc(C(=O)NCCCC(=O)O)c3)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: PAKHFWJSACDCKB-HKBQPEDESA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]D-Trp6-LHRH from human GnRH receptor expressed in CHO-K1 cell membranes incubated for 1 hr by competitive binding assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 724.76, ALogP 4.14, HBA 9, HBD 3, PSA 142.9, QED 0.14
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(CNC(=O)c3ccc(C(=O)NO)cc3)c2c(=O)n1-c1ccccc1
InChIKey: UDIGTKMLGJNRSL-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 590.6, ALogP 2.43, HBA 12, HBD 6, PSA 226.96, QED 0.11
Compound (SMILES): Cc1cn(C23CC(Nc4nc5n(n4)CCCC[C@H]5c4ccc(F)c(F)c4)(C2)C3)cn1
InChIKey: HZFPQLYGOZJEDT-XDGVHFHYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Cellular gamma-Secretase Assay: Human neuroglioma H4 cells overexpressing human APP695 with the Swedish double mutation (K595N/M596L) were plated at 30,000 cells/well/100 μl in 96-well plates in IMDM media containing 10% FCS, 0.2 mg/l Hygromycin B and incubated at 37° C., 5% CO2.3-4 hr post plating, compounds are a diluted in media and 50 μl is added as 1.5-fold concentrate to achieve the final concentration. Compound incubation is performed for 24 hr. Final doses typically range from 4 μM down to 0.001 μM in half-log steps resulting in a eight point dose response curve.Appropriate controls using vehicle only and reference compound were applied to this assay. The final concentration of Me2SO was 0.4%.After incubation at 37° C., 5% CO2, the supernatant was subjected to quantification of secreted Aβ42 by the means of an AlphaLisa assay kit (Human Amyloid beta 1-42 Kit: Cat #AL203C, Perkin Elmer). 20 μl of the cell culture supernatant was transferred to an assay plate. Then 10 μl of a mixture of the AlphaLisa coupled capture antibody and the biotinylated detection antibody was added and incubated for 3 hours at room temperature while softly shaking the assay plate. After a further addition of 20 μl of the Donor beads the assay plate was incubated for 30 min at room temperature and constant shaking without exposure to direct light. The assay plate was then read on a Paradigm AlphaLisa Reader using the build-in program with excitation at 680 nm and emission at 570 nm.The measured signals were then used to calculate IC50 values for inhibition of Aβ42 secretion by nonlinear regression fit analysis using XLfit 5.3 software (IDBS).
Measurement: EC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 410.47, ALogP 4.12, HBA 6, HBD 1, PSA 60.56, QED 0.7
Compound (SMILES): O=C(OC(C(F)(F)F)C(F)(F)F)N1CCN(Cc2ccc(C(F)(F)F)cc2N2CC[C@H](O)C2)CC1
InChIKey: PICHAYNTYNMQDD-AWEZNQCLSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay
Measurement: IC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 523.4, ALogP 4.02, HBA 5, HBD 1, PSA 56.25, QED 0.6
Compound (SMILES): Cc1noc2ccc(Nc3n[nH]c4cccnc34)cc12
InChIKey: FLWCYUXGFBGAIM-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Positive allosteric modulation of human mGlu4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in glutamate-induced calcium mobilization preincubated for 142 secs followed by EC20 glutamate addition and subsequent EC80 glutamate addition after 147 secs by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 = 75.86 nM (pChEMBL 7.119999885559082)
Descriptors: MW 265.28, ALogP 3.15, HBA 5, HBD 2, PSA 79.63, QED 0.58
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)CN2CCOCC2)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]2(C)CO2)cc1
InChIKey: MBSXFXRWARVFLI-ZZUYEWEESA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of catalytic activity of immunoproteasome 20s subunit beta5 in human Raji cells incubated for 1 hr by BODIPY(TMR)-NC-005-VS probe based competitive activity based protein profiling assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 672.82, ALogP 2.82, HBA 8, HBD 3, PSA 138.6, QED 0.2
Compound (SMILES): O=C(O)COc1ccc(OCc2ncc(-c3ccccc3)s2)cc1F
InChIKey: HGPGJOALZXWZIA-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 receptor expressed in CHO cells by Fluo 4-AM dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.38, ALogP 3.99, HBA 5, HBD 1, PSA 68.65, QED 0.69
Compound (SMILES): Cc1[nH]c2c(N3CCCCC3)c(-c3ccccc3)nn2c(=O)c1-c1ccccc1
InChIKey: CUAKSBCCEPGFJH-UHFFFAOYSA-N
Target: S-adenosylmethionine synthase isoform type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31153
Assay: Inhibition of recombinant His6-tagged MAT2A (unknown origin) expressed in SF9 insect cells using L-Met as substrate preincubated for 60 mins followed by substrate and ATP addition and measured after 60 mins by spectrophotometric analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 384.48, ALogP 4.66, HBA 4, HBD 1, PSA 53.4, QED 0.56
Compound (SMILES): CCC(C)(C)c1ccc(OCCCN2CCCCCC2)cc1
InChIKey: ZTOUOCYMUXLHOP-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 303.49, ALogP 5.02, HBA 2, HBD 0, PSA 12.47, QED 0.66
Compound (SMILES): O=c1[nH]c2ccc(-n3nnc4c(Cl)cc(-c5ccnn5Cc5ccc(Cl)cn5)cc43)cc2[nH]1
InChIKey: KFGULMUSOJKNHW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human liver microsome CYP1A2 using phenacetin as substrate incubated for 5 to 20 mins by LC-MS/MS analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 477.32, ALogP 4.2, HBA 7, HBD 2, PSA 110.07, QED 0.4
Compound (SMILES): CC(C)(C)Cc1cnc(CCc2ccc(-c3cccc(F)c3C(=O)O)cc2)n1Cc1ccc(C(=O)O)cc1
InChIKey: XNLXDOOTASTHRA-UHFFFAOYSA-N
Target: Bombesin receptor subtype-3 (SINGLE PROTEIN), Mus musculus
UniProt: O54798
Assay: Agonist activity at mouse BRS3 expressed in CHOK1 cells measured after 1 hrs by IP-One HTRF assay
Measurement: EC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 514.6, ALogP 6.51, HBA 4, HBD 2, PSA 92.42, QED 0.27
Compound (SMILES): O=C(/C=C/c1ccc(OCc2ccccc2)cc1)NCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: XDSJIKQHXRQOIP-KNTRCKAVSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human acetylcholinesterase using acetylthiocholine as substrate pretreated followed by substrate addition and measured after 15 mins by Ellman's method
Measurement: IC50 = 60.6 nM (pChEMBL 7.21999979019165)
Descriptors: MW 477.61, ALogP 5.93, HBA 4, HBD 2, PSA 63.25, QED 0.23
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cccc(N(C)C)c2)o1
InChIKey: VUKPJINUBVOFGY-GOSISDBHSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 444.53, ALogP 2.86, HBA 6, HBD 3, PSA 115.12, QED 0.14
Compound (SMILES): O=S(=O)(c1ccncc1)c1ccc(N2CC(CN3CCC(C4(C5CCCC5)CN(C5CCC5)Cc5ccccc54)CC3)C2)cc1
InChIKey: AZMLEISFRDLXOA-UHFFFAOYSA-N
Target: Menin (SINGLE PROTEIN), Homo sapiens
UniProt: O00255
Assay: Inhibition of FAM-probe binding to Menin (unknown origin) after 60 mins by fluorescence polarization competitive binding assay
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 624.9, ALogP 6.56, HBA 6, HBD 0, PSA 56.75, QED 0.28
Compound (SMILES): O=C(c1cc2ccccc2[nH]1)N1CCN(CCOc2ccccn2)CC1
InChIKey: MOUIWMOQLHUNKH-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2R expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 120 mins by beta-galactosidase based PathHunter assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 350.42, ALogP 2.4, HBA 4, HBD 1, PSA 61.46, QED 0.77
Compound (SMILES): O=C(NCc1ncccc1F)c1csc(CCNCc2cccc3[nH]cnc23)n1
InChIKey: VMESCFXCOVWUMB-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as reduction in Fpn-mediated iron efflux incubated overnight by iron regulatory element -driven beta-lactamase reporter gene assay
Measurement: EC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 410.48, ALogP 2.82, HBA 6, HBD 3, PSA 95.59, QED 0.39
Compound (SMILES): CC(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C1=O
InChIKey: CJDDQXAFRANGRP-SUMWPZCCSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Mus musculus
UniProt: P06869
Assay: Binding affinity to mouse uPA expressed in HEK2936E cells by ITC assay
Measurement: Kd = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 1229.41
Compound (SMILES): CC1=C(C#N)[C@@H](c2ccc3[nH]nc(C)c3c2)C(C#N)=C(c2ccc(Cl)cc2)N1
InChIKey: BGQYHBPBRKOJMZ-OAQYLSRUSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: GPCRScan assay: inhibition of 5-HT2C
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 385.86, ALogP 4.94, HBA 4, HBD 2, PSA 88.29, QED 0.65
Compound (SMILES): Cc1nc2sc3c(NCC4CC4)nn(C)c3c2c(C)c1Cl
InChIKey: MEKMMZISKWWYPV-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 320.85, ALogP 4.28, HBA 5, HBD 1, PSA 42.74, QED 0.78
Compound (SMILES): CC(C)(C)OC(=O)N1CCc2ccc(N)cc2C1
InChIKey: AGRBXKCSGCUXST-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at recombinant human LXRbeta-LBD expressed in Escherichia coli BL21 (DE3) assessed as peptide D22 recruitment fluorescence polarization binding assay
Measurement: EC50 = 57000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 248.33, ALogP 2.56, HBA 3, HBD 1, PSA 55.56, QED 0.72
Compound (SMILES): C=CC(=O)N1CC(NC(=O)Cn2cc(C(=O)N(C)Cc3ccccc3)c3cc(Br)ccc32)C1
InChIKey: AVLGQWHCPAUISH-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human MIAPaCa2 cells assessed as reduction in EGF-induced ERK1/2 phosphorylation incubated for 4 hrs followed by EGF addition by luminescence based assay
Measurement: IC50 = 52700 nM (pChEMBL 4.28000020980835)
Descriptors: MW 509.4, ALogP 3.19, HBA 4, HBD 1, PSA 74.65, QED 0.5
Compound (SMILES): CCCn1c(NC(=O)c2ccnn2C)nc2cc(C(N)=O)cc(OC)c21
InChIKey: KPIQJZVLZKAHMQ-UHFFFAOYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING in human THP1 cells assessed as stimulation of IRF3 pathway measured after 20 hrs by luciferase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 356.39, ALogP 1.54, HBA 7, HBD 2, PSA 117.06, QED 0.69
Compound (SMILES): O=C1Cc2cc(-c3c(-c4ccc(F)cc4)nc4c(N5CCC(F)CC5)nccn34)ccc2N1
InChIKey: CQHVKBXXQZUVDK-UHFFFAOYSA-N
Target: GRIA1/CACNG2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y698
Assay: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 445.47, ALogP 4.64, HBA 5, HBD 1, PSA 62.53, QED 0.5
Compound (SMILES): Cc1ccc(-c2cn(Cc3ccc(S(N)(=O)=O)cc3)nn2)cc1C(=O)NCCN1CCOCC1
InChIKey: HIJYGMPIRGCJRS-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE preincubated for 6 mins followed by addition of acetylthiocholine iodide by Ellman's method
Measurement: IC50 = 30330 nM (pChEMBL 4.519999980926514)
Descriptors: MW 484.58, ALogP 1.01, HBA 8, HBD 2, PSA 132.44, QED 0.49
Compound (SMILES): O=C(c1cnn(-c2nc3c(c(=O)[nH]2)CCC3)c1)N1CCN(c2ccc(F)cc2F)CC1
InChIKey: YKRDMNWVILVWIW-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 426.43, ALogP 1.68, HBA 6, HBD 1, PSA 87.12, QED 0.69
Compound (SMILES): Cc1c(C(=O)N2CCC(n3ccc(S(=O)(=O)C(F)(F)F)c3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: JZBJMMVGVRGURL-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 523.5, ALogP 2.09, HBA 9, HBD 1, PSA 127.36, QED 0.44
Compound (SMILES): CCCCN(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1nc2cc(CC(=O)OC)ccc2o1
InChIKey: ONDKMHVLMLPZCK-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Inhibition of CXCR4 expressed in human CAL1 cells assessed as reduction in SDF1alpha-induced intracellular calcium ion concentration preincubated for 45 mins followed by SDF1alpha addition
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 496.57, ALogP 5.2, HBA 8, HBD 1, PSA 110.03, QED 0.26
Compound (SMILES): CC(C)(c1cc([C@@]23CCOC[C@@H]2C3)nc(-c2cccc(O)c2)n1)S(C)(=O)=O
InChIKey: UGPOTDKTCTWFSI-VBKZILBWSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 388.49, ALogP 2.81, HBA 6, HBD 1, PSA 89.38, QED 0.87
Compound (SMILES): CC(=O)NC1=NN(c2ccc(Cl)c(Cl)c2)[C@H](C)C1
InChIKey: AIMHJXGSTIXRJW-SSDOTTSWSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Displacement of Myr-GQQPGKVLGDQRRPSL(K-TAMRA)G-amide from N-terminal-truncated human c-ABL D382N mutant (46 to 534 residues) after 30 mins by fluorescence polarization binding assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 286.16, ALogP 3.04, HBA 3, HBD 1, PSA 44.7, QED 0.86
Compound (SMILES): CCN1CCN(CCCNC(=S)Nc2ccc3nc(N(C)CCN)cc(C)c3c2)CC1
InChIKey: WRFGNVYCIZZKQA-UHFFFAOYSA-N
Target: DNA repair protein RAD52 homolog (SINGLE PROTEIN), Homo sapiens
UniProt: P43351
Assay: Inhibition of RAD52 (unknown origin) assessed as effect on ssDNA annealing using ssDNA oligonucleotide by fluorescence-quenching assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 443.67, ALogP 2.25, HBA 6, HBD 3, PSA 72.69, QED 0.4
Compound (SMILES): O[C@H]1[C@H](n2cnc3c(NC(C4CCC4)C4CCC4)nc(Cl)nc32)[C@H]2C[C@@]2(CCl)[C@H]1O
InChIKey: BEQHYAAIFYRXLC-MXKWNSRKSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Mus musculus
UniProt: Q60612
Assay: Displacement of [3H]N6-R-phenylisopropyladenosine from mouse A1A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 11.2 nM (pChEMBL 7.949999809265137)
Descriptors: MW 452.39, ALogP 3.38, HBA 7, HBD 3, PSA 96.09, QED 0.46
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1ccc(OS(=O)(=O)O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: FCDAJLCDHWZLKC-ASNOGBRRSA-N
Target: Gastrin/cholecystokinin type B receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P32239
Assay: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay
Measurement: IC50 = 0.1318 nM (pChEMBL 9.880000114440918)
Descriptors: MW 1839.09
Compound (SMILES): C[C@@H]1CN(c2ccc(C(=O)N[C@@H]3CCN(C#N)C3)cc2F)C[C@H](C)O1
InChIKey: KIKXBSPVKMTGPW-VNHYZAJKSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 346.41, ALogP 1.72, HBA 5, HBD 1, PSA 68.6, QED 0.84
Compound (SMILES): CCn1nc(C)cc1C(=O)/N=c1\[nH]c2cc(C(N)=O)ccc2n1C[C@@H](O)c1ccccc1
InChIKey: NMXJYHHOVIHSBO-HXUWFJFHSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Inhibition of human wild type STING
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 432.48, ALogP 2.07, HBA 6, HBD 3, PSA 131.29, QED 0.43
Compound (SMILES): Oc1ccc2c(c1)CCCC(c1ccc(OC(F)(F)F)cc1)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: CUVIEOMIPZIETH-MHZLTWQESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Estrogen Receptor Coactivator Assay: It is a competition assay, where binding of a test compound to a complex comprised of (i) His6-ERα298-554 protein representing ERα ligand-binding domain, (ii) Tb-labeled His6 antibody, (iii) a fluorescein-labeled PGC1α coactivator peptide (EAEEPSLLKKLLLAPANTQ), and (iv) estradiol, results in a decrease of the TR-FRET signal due to dissociation of the coactivator peptide. His6-ERα298-554 proteins were expressed as WT or D538G or Y537S mutants in E. coli and purified by affinity chromatography. The assay works in a homogeneous mix-and-read format. In a typical experiment, a 4 μL mixture of 0.5 nM His6-ERα298-554, 0.5 nM Tb-labeled His6 antibody, 250 nM PGC1a peptide, and 3 nM estradiol in 100 mM potassium phosphate, pH 7.4, 0.01% Tween-20, 0.02% NaN3, 5 mM DTT, was added to 40 nL test compound in DMSO and incubated overnight at room temperature. The TR-FRET 520:495 nm emission ratio was calculated and used to determine the IC50 value from a dose response curve fit to the 4-parameter logistic equation. The antagonist activity with respect to estrogen receptors in this test is given by the concentration which inhibits 50% of the estrogen receptor activity (or IC50) in nM.
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 541.59, ALogP 7.4, HBA 4, HBD 1, PSA 41.93, QED 0.3
Compound (SMILES): CCCCNC(=O)C#Cc1cc(C2=NN(C(C)C)C(=O)[C@@H]3CC=CC[C@H]23)ccc1OC
InChIKey: QNGCEEKDIHUHQH-LEWJYISDSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B catalytic domain using cAMP as substrate incubated for 20 mins by PDELight HTS cAMP phosphodiesterase Kit based luminometry
Measurement: Ki = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 421.54, ALogP 3.5, HBA 4, HBD 1, PSA 71, QED 0.43
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccc(C(=O)NC4CC(C)(C)N([O])C(C)(C)C4)cc3)ncc2F)no1
InChIKey: VCRPHLZHPCWATH-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of aurora B (unknown origin) using Kemptide as substrate after 60 mins by ADP-Glo luminescence assay
Measurement: IC50 = 17.3 nM (pChEMBL 7.760000228881836)
Descriptors: MW 482.54, ALogP 4.5, HBA 8, HBD 3, PSA 128.11, QED 0.47
Compound (SMILES): CC(=O)N1CCN(c2ccc(CN3C[C@H](C)OC[C@H](c4ccccc4)S3(=O)=O)c(F)c2)CC1
InChIKey: KKPFRRKOLHWVLL-MHECFPHRSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4-fused human RORc expressed in HEK293 cells assessed as activation of basal transcriptional activity by dual-glo luciferase reporter gene assay
Measurement: EC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 475.59, ALogP 2.79, HBA 5, HBD 0, PSA 70.16, QED 0.68
Compound (SMILES): Cc1cccc(C#CC=C2CCN(S(=O)(=O)c3cccc(Br)c3)CC2)n1
InChIKey: RYONOLMMZJYWEO-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Negative allosteric modulation of human mGlu5 receptor expressed in CHO-TREx cell membranes assessed as reduction in quisqualate-induced Ca2+ mobilization incubated for 18 hrs and measured every 1.5 secs intervals for 60 secs by Fluo-4/AM dye-based fluorescence analysis
Measurement: IC50 = 89.9 nM (pChEMBL 7.050000190734863)
Descriptors: MW 431.36, ALogP 3.92, HBA 3, HBD 0, PSA 50.27, QED 0.68
Compound (SMILES): COc1cccc(N2C(=O)COc3ccc(-c4cnc5ccccc5c4)cc32)c1
InChIKey: YONVDRWHELRNBQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human N-terminal FLAG-tagged mTOR (1362 to end residues) using Ulight-4E-BP1 as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.42, ALogP 4.97, HBA 4, HBD 0, PSA 51.66, QED 0.5
Compound (SMILES): C/C(=N\NC(=O)c1nc(N)n(-c2ccc(S(N)(=O)=O)cc2)n1)c1ccccc1
InChIKey: DPLMSZXNZDXGHI-SRZZPIQSSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 41.3 nM (pChEMBL 7.380000114440918)
Descriptors: MW 399.44, ALogP 0.65, HBA 8, HBD 3, PSA 158.35, QED 0.42
Compound (SMILES): O=C1NC(c2ccc(N3CCCCC3)cc2)(c2ccsc2)CC(O)=C1Sc1ccccc1Cl
InChIKey: OSCRHRYASAHIKU-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MiPaca2 cells assessed as inhibition of lactate production
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 497.09, ALogP 6.72, HBA 5, HBD 2, PSA 52.57, QED 0.41
Compound (SMILES): O=C1c2ccccc2Nc2ccc(F)cc2N1Cc1ccccc1
InChIKey: NKFCUHMOEKHJLB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as reduction in cell growth incubated for 72 hrs in presence of 1 ug/ml Cetuximab by celltiter-glo luminescent cell viability assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 318.35, ALogP 4.73, HBA 2, HBD 1, PSA 32.34, QED 0.74
Compound (SMILES): N#CCC(=O)Nc1nsc(-c2ccc(Cl)c(Cl)c2)n1
InChIKey: VZCGBSAPBTXWAE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Induction of human c-ABL phosphorylation at Y245/Y412 residues in bacmam-induced HEK-MSR2 cell lysates by in-cell Western blot analysis
Measurement: EC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 313.17, ALogP 3.36, HBA 5, HBD 1, PSA 78.67, QED 0.94
Compound (SMILES): CC[C@@H]1[C@H](F)C(=O)N[C@@H]1COc1cccc2cc(C(N)=O)c(OC)cc12
InChIKey: HVYXXOWVKHZMEJ-KHIZAZIESA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: IRAK4 Enzymatic DELFIA Assay, Protocol B: This is an in vitro assay to measure IRAK4 enzymatic activity utilizing the DELFIA (Dissociation-Enhanced Lanthanide Fluorescent Immunoassay, Perkin-Elmer) platform, with inactive, unphosphorylated (0-phos), human IRAK4 FL (Full Length) construct to characterize IRAK4 inhibitor and control compounds at 600 μM ATP (KM). The final amount of enzyme in the assay is 0.1 nM inactive, 0-phos, IRAK4 FL, final concentration of substrate is 50 nM, and final concentration of DMSO is 2.5%.The test compound is solubilized in DMSO to a stock concentration of 30 mM. The dose response plates were prepared with a 4 mM primary compound concentration, serialized in DMSO and spotted (1 μL) into 384-well polypropylene plates as before.To begin the assay, 19 uL of reaction mixture containing 20 mM HEPES pH=7.5, 5 mM MgCl2, 0.0025% Brij-35, 600 uM ATP, 0.21 nM inactive, 0-phos, full-length recombinant human IRAK4 (GenBank ID AF445802) were aliquoted into the polypropylene plates containing 1 μL of test compound as before. 20 uL of 20 mM HEPES pH=7.5, 5 mM MgCl2, 0.0025% Brij-35, 600 μM ATP, and 100 nM ERM-biotinylated peptide (AGAGRDKYKTLRQIR) was added to start the reaction, which was run for 90 minutes at RT and stopped by the addition of 20 μL 0.3M EDTA.50 μL of the reaction mixture was transferred to a streptavidin-coated detection plate (DELFIA streptavidin coated plates, 384-well, white plates, Perkin-Elmer Life Sciences) and incubated for 30 minutes at RT. The plates were washed 4× with 75 μL per well of PBS containing 0.05% Tween-20. Plates were then incubated with 50 μL per well of antibody cocktail of Anti-pERM antibody at 0.125 μg/mL (Cell Signaling Technology), plus Anti-Rabbit IgG EuN1 at 0.25 μg/ml (Perkin-Elmer Life Sciences) in a solution of 10 mM MOPS pH=7.5, 150 mM NaCl, 0.05% Tween-20, 0.02% NaN3, 1% BSA, 0.1% Gelatin for 45 minutes. The plates were then washed as before. 50 μL per well of DELFIA Enhancement Solution (Perkin-Elmer Life Sciences) was added to the plate and incubated for 15 minutes at RT prior to being read on an Envision Model 2104 multi-label reader using a 340 nm excitation wavelength and a 665 nm emission wavelength for detection.
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 360.39, ALogP 2.19, HBA 4, HBD 2, PSA 90.65, QED 0.83
Compound (SMILES): FC(F)(F)Cc1cc2c(N[C@H]3CC[C@H](CN[C@@H]4C[C@H]4c4ccccc4)CC3)ncnc2s1
InChIKey: BWWSOKMEUMJPCJ-WRGRXTPVSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of MAOB (unknown origin) by Promega MAO-Glo assay
Measurement: IC50 = 4810 nM (pChEMBL 5.320000171661377)
Descriptors: MW 460.57, ALogP 5.91, HBA 5, HBD 2, PSA 49.84, QED 0.46
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(CS(=O)(=O)O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N(C)[C@H](CC(=O)O)C(=O)N(C)[C@@H](Cc1ccccc1)C(N)=O
InChIKey: SONXBYYPVLEZOJ-ZOEGOAMBSA-N
Target: Cholecystokinin receptor type A (SINGLE PROTEIN), Homo sapiens
UniProt: P32238
Assay: Agonist activity at human CCK1R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay
Measurement: EC50 = 0.1905 nM (pChEMBL 9.720000267028809)
Descriptors: MW 1821.12
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)/C(Cl)=N/Nc2ccc(F)cc2)cc1
InChIKey: AJLMUGVHFFKXAC-MOSHPQCFSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7380 nM (pChEMBL 5.130000114440918)
Descriptors: MW 370.79, ALogP 2.08, HBA 5, HBD 3, PSA 113.65, QED 0.55
Compound (SMILES): COc1ccc(NC(=O)Nc2ccc(CCc3nc4ccccc4n3C)cc2)c(OC)c1
InChIKey: ULWPMMLBROFLBJ-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged recombinant human ATP-activated TRKA kinase domain (441 to 796 residues) expressed in baculovirus expression system preincubated with enzyme/ATP mixture for 20 mins followed by TK substrate-biotin addition followed by further incubation for 15 mins in presence of ATP by HTRF assay
Measurement: IC50 = 405.4 nM (pChEMBL 6.389999866485596)
Descriptors: MW 430.51, ALogP 5.02, HBA 5, HBD 2, PSA 77.41, QED 0.43
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(O[C@@H]4CCOC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: OBWASQILIWPZMG-VUOLKEHKSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition of human SGLT2
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 450.92, ALogP 1.61, HBA 7, HBD 4, PSA 108.61, QED 0.53
Compound (SMILES): NCc1ccc(S(=O)(=O)Cc2ccccc2)s1
InChIKey: RQFDYTYGIXKANU-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: LOX Enzyme Activity Assay: The following reagents were prepared:Reagents500 mM CHES, pH 9 (with NaOH), filtered (MW=207.29)20.7 g in 200 ml in dH2O10% Pluronic F-127 (store at 4° C.)1 g in 10 ml in dH2O10 % BSA (store at 4° C.)−2.5 g in 25 ml dH2O1 M MgCl2.6H2O (MW=203)5.1 g in 25 ml dH2O5 M Urea (MW=60.06)60 g in 200 ml dH2O5 M NaCl (MW=58.44)14.6 g in 50 ml dH2O8.5 M Cadaverine Dihydrochloride (MW=175.10): Sigma, Cat No: C85611.49 g in 1 ml dH2O10 mM Na3VO4, pH 10 (with HCl), boil to activate (MW=183.91): Sigma, Cat No: S65080.1839 g in 10 ml dH2O20 mM Amplex Red (MW=257.25): Invitrogen, Cat No: A12222.5 mg in 1 ml DMSO (aliquot into 40 μl and store at −20° C.)1000 U/ml HRP in dH2O (store at 4° C.): Sigma, Cat No: P2088H2O2 (store at 4° C.): Sigma, Cat No: H1009DMSOLOX Assay Buffer: Volume (μl) Reagent 1 × plate Final Concn 500 mM CHES, pH 9 5000 100 mM 10% Pluronic F-127 125 0.05% 10% BSA 1250 0.5% 1M MgCl2 25  1 mM 5M Urea 5000 1M 5M NaCl 500 100 mM dH2O 13100 — Total Volume 25 000 —Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.LOX enzyme:LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (˜4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls: 0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final Concn Assay Buffer 2 ml 3 ml — 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM 20 mM Amplex Red 10 μl 15 μl 100 μM 1000 U/ml HRP 10 μl 15 μl 5 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader: Excitation wavelength: 545 nm Emission wavelength: 585 nm HRP Counter Assay Protocol1. Dilute 5 μl H2O2 in 640 μl dH2O. Add 1 μl diluted H2O2 to 10 ml Assay Buffer. Vortex2. Add 40 μl H2O2+Assay Buffer into every well on the counter assay plate EXCEPT no H2O2 control wells (add 40 μl Assay Buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of positive control, Na3VO4, down column 11 (no duplication)5. Add following controls: 0.5 μl DMSO (100% activity control) 1 μl diluted H2O2 (blow out control)6. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 267.37, ALogP 2.18, HBA 4, HBD 1, PSA 60.16, QED 0.92
Compound (SMILES): COc1ccccc1-c1cc(CN2C(=O)c3ccccc3S2(=O)=O)on1
InChIKey: OOAQTGMDIZUXLL-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 370.39, ALogP 2.69, HBA 6, HBD 0, PSA 89.71, QED 0.7
Compound (SMILES): O=C(O)c1ccccc1Nc1c(Cl)cc(-c2ccncc2)cc1Cl
InChIKey: GSNZPZDSMBVGPU-UHFFFAOYSA-N
Target: Alpha-ketoglutarate-dependent dioxygenase FTO (SINGLE PROTEIN), Homo sapiens
UniProt: Q9C0B1
Assay: Inhibition of FTO (unknown origin) assessed as reduction in demethylation using 39nt-m6 A-ssDNA and 2OG incubated for 2 hrs by non-denaturing polyacrylamide electrophoresis method
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 359.21, ALogP 5.5, HBA 3, HBD 2, PSA 62.22, QED 0.65
Compound (SMILES): CN1C(=O)NS(=O)(=O)c2ccccc21
InChIKey: RQCMUVKZNMGOOY-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 1 hr prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 3459 nM (pChEMBL 5.460000038146973)
Descriptors: MW 212.23, ALogP 0.53, HBA 3, HBD 1, PSA 66.48, QED 0.68
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(C)(C)C(=O)O)cc2)o1)[C@@H](CC)N(O)C=O
InChIKey: CSOOXMLPHMLROL-NHCUHLMSSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 515.61, ALogP 3.94, HBA 6, HBD 4, PSA 149.18, QED 0.09
Compound (SMILES): Cc1ccc(Cn2cc(CNC3=C(Cl)C(=O)c4cccnc4C3=O)nn2)cc1
InChIKey: BDBIMDYALUJAPR-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of recombinant human Cdc25A using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 393.83, ALogP 2.65, HBA 7, HBD 1, PSA 89.77, QED 0.72
Compound (SMILES): Cc1cc(C)cc(Nc2nccc(-c3c(-c4ccc(F)cc4)ncn3C3CCNCC3)n2)c1
InChIKey: DGOVBHLIYNOJOQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 N-terminal bromodomain 1 (unknown origin) expressed in Escherichia coli Bl21(DE3) by alpha-screen assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 442.54, ALogP 5.43, HBA 6, HBD 2, PSA 67.66, QED 0.43
Compound (SMILES): COc1ncc(-c2cc3c(c(NC(=O)CC4CCOCC4)c2)COC3)cc1NS(C)(=O)=O
InChIKey: LXXXCAGCXBZYMJ-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110beta/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of biotin-PIP3 by HTRF assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 461.54, ALogP 2.91, HBA 7, HBD 2, PSA 115.85, QED 0.65
Compound (SMILES): CCc1ccc(NC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@H]2COC(=O)[C@@H]3C[C@@H](C)CN3C(=O)[C@H](C)NC(=O)[C@@H]3CCCCN3C(=O)[C@@H]3CCCN3C2=O)cc1
InChIKey: XTGQQKUGSYCDBD-KRCFFJRGSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Activation of Staphylococcus aureus ClpP using BODIPY-FL-casein as substrate incubated for 30 mins by Enz-Check protease assay
Measurement: EC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 771.92, ALogP 2.14, HBA 8, HBD 4, PSA 186.56, QED 0.31
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NC3(C)CC3(F)F)cc12
InChIKey: QFCYAHVJEFQNHG-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: Compound dilution series were prepared in DMSO via an approximately 3-fold serial dilution. Compound dilutions were added directly into white, low-volume assay plates (Perkin Elmer Proxiplate 384 Plus#6008280) using a Labcyte Echo in conjunction with Labcyte Access and Thermo Multidrop CombinL robotics. Compounds were then suspended in eight microliters (μL) of assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and Alexa-647-conjugated probe.The final concentration of 1× assay mixture contained 2% DMSO, 12 nM His tagged BRD4 (BDI_K57-E168) and 100 nM probe or 4 nM His tagged BRD4 (BDII_E352-M457) and 30 nM probe, and 1 nM Europium-conjugated anti-His-tag antibody, and compound concentrations in the range of: 49.02 μM-0.61 nM or 0.98 μM-0.15 nM.After a one-hour equilibration at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki = 3510 nM (pChEMBL 5.460000038146973)
Descriptors: MW 553.58, ALogP 5.84, HBA 5, HBD 3, PSA 96.35, QED 0.28
Compound (SMILES): N#Cc1cccc(CSc2nc(N)c(C#N)c(-c3ccco3)c2C#N)c1
InChIKey: IYIVPBBGRWZCSP-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]ABMECA from human A3R expressed in CHO cell membranes measured after 120 mins by scintillation counting method
Measurement: Ki = 668 nM (pChEMBL 6.170000076293945)
Descriptors: MW 357.4, ALogP 3.83, HBA 7, HBD 1, PSA 123.42, QED 0.7