lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): c1ccc(C2C[C@@H]2NCc2ccc3ccccc3n2)cc1
InChIKey: WAFRFMFYPAXOSB-NNBQYGFHSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 274.37, ALogP 3.88, HBA 2, HBD 1, PSA 24.92, QED 0.78
Compound (SMILES): COc1ncccc1CN[C@H]1CC1c1ccccc1
InChIKey: NPKNICGBPBZUFV-LOACHALJSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 254.33, ALogP 2.74, HBA 3, HBD 1, PSA 34.15, QED 0.89
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)cc1OC
InChIKey: GBKSTZVWUQFBQJ-LYKKTTPLSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 283.37, ALogP 3.35, HBA 3, HBD 1, PSA 30.49, QED 0.88
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)cc1F
InChIKey: OPSGFELBTCGXLT-WMCAAGNKSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 271.34, ALogP 3.48, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): COc1ccccc1CN[C@H]1CC1c1ccc(OCc2ccccc2)cc1
InChIKey: PPCBJIQRKKFFJQ-WCSIJFPASA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 359.47, ALogP 4.92, HBA 3, HBD 1, PSA 30.49, QED 0.62
Compound (SMILES): COc1ccc(CC(C)N[C@H]2CC2c2ccccc2)cc1OC
InChIKey: FZKMYHFPTZQCSK-UYJHFMRCSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 311.43, ALogP 3.78, HBA 3, HBD 1, PSA 30.49, QED 0.84
Compound (SMILES): C[Si](C)(C)C1=C2c3nc4ccccc4cc3C(O)CC2CC1=O
InChIKey: OIIOPIIGGQSDJQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 323.47
Compound (SMILES): CN(C)[C@H]1CCN(C(=O)CN[C@H]2C[C@@H]2c2ccccc2)C1
InChIKey: JVXIYDJULSGMQC-XHSDSOJGSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Biological Assay: Biological assay using monoamine oxidase or LSD1.
Measurement: Ki = 221 nM (pChEMBL 6.659999847412109)
Descriptors: MW 287.41, ALogP 1.29, HBA 3, HBD 1, PSA 35.58, QED 0.89
Compound (SMILES): O=C(CN[C@H]1C[C@@H]1c1ccccc1)N1CCN(Cc2ccccc2)CC1
InChIKey: NQNAAQHKTOHNRL-RTWAWAEBSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Biological Assay: Biological assay using monoamine oxidase or LSD1.
Measurement: Ki = 1040 nM (pChEMBL 5.980000019073486)
Descriptors: MW 349.48, ALogP 2.48, HBA 3, HBD 1, PSA 35.58, QED 0.87
Compound (SMILES): CN1CCN(C(=O)CN[C@H]2C[C@@H]2c2ccc(OCc3ccccc3)cc2)CC1
InChIKey: YAMSXCOVJUUMCT-YADHBBJMSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Biological Assay: Biological assay using monoamine oxidase or LSD1.
Measurement: Ki = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 379.5, ALogP 2.49, HBA 4, HBD 1, PSA 44.81, QED 0.8
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of Tel fused InsR (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay
Measurement: IC50 = 429 nM (pChEMBL 6.369999885559082)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](O)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: WUOBKQMEZQEJEO-ZNMIVQPWSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 441.45, ALogP 5.08, HBA 4, HBD 2, PSA 75.11, QED 0.59
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@@H]1O
InChIKey: HIRGJKYVLHTQTI-NBDAELCASA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 456.47, ALogP 4.01, HBA 5, HBD 3, PSA 101.13, QED 0.55
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3ccccc3F)n2)C1
InChIKey: ATNCLUHEGCYVPT-XHSDSOJGSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 422.48, ALogP 4.91, HBA 4, HBD 2, PSA 80.9, QED 0.63
Compound (SMILES): Nc1cc(F)c(-c2c(F)cccc2F)nc1C(=O)Nc1cnccc1[C@@H]1CC[C@H](O)[C@H](N)C1
InChIKey: RXCHWYUVXYDNBW-RWTORFTKSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 457.46, ALogP 3.35, HBA 6, HBD 4, PSA 127.15, QED 0.48
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of PIM2 kinase (unknown origin) using NH2-AGAGRSRHSSYPAGT-OH as substrate by kinase-Glo assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): N[C@H]1CCC[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: KMEWOQDIZJORND-KGLIPLIRSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of PIM2 kinase (unknown origin) using NH2-AGAGRSRHSSYPAGT-OH as substrate by kinase-Glo assay
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 426.44, ALogP 4.8, HBA 4, HBD 2, PSA 80.9, QED 0.63
Compound (SMILES): Nc1ccc(C2CCCCC2)nc1C(=O)Nc1cnccc1[C@@H]1CCC[C@H](N)C1
InChIKey: AKRXLINEJRYTHQ-SJORKVTESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of PIM2 kinase (unknown origin) using NH2-AGAGRSRHSSYPAGT-OH as substrate by kinase-Glo assay
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 393.54, ALogP 4.34, HBA 5, HBD 3, PSA 106.92, QED 0.72
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](O)[C@@H]1O
InChIKey: AISMIGRIJQYZHW-NXTZNFLJSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of PIM2 (unknown origin) using Bad peptide NH2-AGAGRSRHSSYPAGT-OH as substrate measured after 10 mins in presence of ATP by luciferase-luciferin based Kinase-Glo luminescence assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 457.45, ALogP 4.05, HBA 5, HBD 3, PSA 95.34, QED 0.55
Compound (SMILES): Cc1nn(C2CCCCC2)c2sc(C(=O)Nc3ccc(N4CCC(O)CC4)c(F)c3)cc12
InChIKey: QYHFUBZVWDZWRK-UHFFFAOYSA-N
Target: Phosphodiesterase 4B (SINGLE PROTEIN), Mus musculus
UniProt: Q8VBU5
Assay: Inhibition Assay: The PDE 4 (phosphodiesterase IV) inhibiting effect of the compounds of the present invention was performed by the following method, which was modified assay method described in Biochemical. Pharmacol. 48(6), 1219-1223 (1994).  (1) The active fraction of PDE 4 (phosphodiesterase IV) was obtained. That is, the livers obtained from three Balb/c mice (male, 12 weeks: obtainable from CLEA Japan, Inc.) were suspended with 30 mL of buffer solution B [20 mM of bis-tris, 5 mM of 2-mercaptoethnol, 2 mM of benzamidine, 2 mM of EDTA, 0.1 mM of 4-(2-aminoethyl)benzensulfonyl hydrochloride, 50 mM of sodium acetate; pH 6.5], then homogenized by Polytron homogenizer. The homogenate were centrifuged under 25,000xG for 10 minutes at 4 C. The supernatant was separated and thus obtained supernatant was further centrifuged under 100,000xG for 60 minutes at 4Â° C., and then filtrated with 0.2 um filter to obtain the soluble fraction.
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 456.59, ALogP 5.26, HBA 6, HBD 2, PSA 70.39, QED 0.56
Compound (SMILES): CS(=O)(=O)c1ccc(Nc2nn([C@@H]3CCCC[C@H]3C#N)cc2C(N)=O)cc1
InChIKey: YIKWKYDCXBWSII-BLLLJJGKSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 387.47, ALogP 2.38, HBA 7, HBD 2, PSA 130.87, QED 0.81
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC(Cc1ccccc1)C21COC1
InChIKey: STMXAUVFLJMWDN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 = 7730 nM (pChEMBL 5.110000133514404)
Descriptors: MW 414.47, ALogP 2.7, HBA 7, HBD 1, PSA 91.85, QED 0.71
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(Cc2ccccc2)O3)c1
InChIKey: UZRCBYZWOAYXCE-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 451.53, ALogP 3.68, HBA 6, HBD 1, PSA 78.96, QED 0.61
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC(CC1CC1)C21COC1
InChIKey: MSVXPEWIJQOLDG-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 378.43, ALogP 2.26, HBA 7, HBD 1, PSA 91.85, QED 0.88
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(Cl)cn3)cc2[C@@]2(COC(N)=N2)C12COC2
InChIKey: INWIVMOTHPFWNU-NRFANRHFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 428.88, ALogP 2.72, HBA 7, HBD 2, PSA 108.06, QED 0.76
Compound (SMILES): Cc1[nH]nc2c1C(c1ccc(Cl)cc1)N(c1cc(C)c(=O)n(C)c1)C2=O
InChIKey: GXKIVKDALCGWBS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 368.82, ALogP 3.13, HBA 4, HBD 1, PSA 70.99, QED 0.76
Compound (SMILES): Cn1cc(N2C(=O)c3nn(C4CC4)cc3C2c2ccc(Cl)cc2)cc(Cl)c1=O
InChIKey: RQSRLTLIMDDPDM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 415.28, ALogP 3.97, HBA 5, HBD 0, PSA 60.13, QED 0.65
Compound (SMILES): COc1ncc(-n2nc3c(c2C)C(c2ccc(Cl)cc2)N(c2cc(Cl)c(=O)n(C)c2)C3=O)c(OC)n1
InChIKey: IBJLUHJBIGMOMD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 527.37, ALogP 3.74, HBA 9, HBD 0, PSA 104.37, QED 0.39
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: NJPHKVOXHRAPGJ-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human whole blood CD3+/CD4+ T cells assessed as reduction in IL7-stimulated STAT5 phosphorylation
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 350.38, ALogP 3.32, HBA 5, HBD 2, PSA 96.97, QED 0.54
Compound (SMILES): C[Si](C)(C)C1=C2c3nc4ccccc4cc3C(O)CC2CC1=O
InChIKey: OIIOPIIGGQSDJQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 323.47
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin)
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](O)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: WUOBKQMEZQEJEO-ZNMIVQPWSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 441.45, ALogP 5.08, HBA 4, HBD 2, PSA 75.11, QED 0.59
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@@H]1O
InChIKey: HIRGJKYVLHTQTI-NBDAELCASA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 456.47, ALogP 4.01, HBA 5, HBD 3, PSA 101.13, QED 0.55
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2nc(-c3c(F)cccc3F)c(F)cc2N)C1
InChIKey: BTGLPUGPEBTEHU-MJBXVCDLSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 455.48, ALogP 4.63, HBA 5, HBD 3, PSA 106.92, QED 0.53
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3ccccc3F)n2)C1
InChIKey: ATNCLUHEGCYVPT-XHSDSOJGSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 422.48, ALogP 4.91, HBA 4, HBD 2, PSA 80.9, QED 0.63
Compound (SMILES): Nc1cc(F)c(-c2c(F)cccc2F)nc1C(=O)Nc1cnccc1[C@@H]1CC[C@H](O)[C@H](N)C1
InChIKey: RXCHWYUVXYDNBW-RWTORFTKSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 457.46, ALogP 3.35, HBA 6, HBD 4, PSA 127.15, QED 0.48
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of PIM3 kinase (unknown origin) using NH2-AGAGRSRHSSYPAGT-OH as substrate by kinase-Glo assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): N[C@H]1CCC[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: KMEWOQDIZJORND-KGLIPLIRSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of PIM3 kinase (unknown origin) using NH2-AGAGRSRHSSYPAGT-OH as substrate by kinase-Glo assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 426.44, ALogP 4.8, HBA 4, HBD 2, PSA 80.9, QED 0.63
Compound (SMILES): Nc1ccc(C2CCCCC2)nc1C(=O)Nc1cnccc1[C@@H]1CCC[C@H](N)C1
InChIKey: AKRXLINEJRYTHQ-SJORKVTESA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of PIM3 kinase (unknown origin) using NH2-AGAGRSRHSSYPAGT-OH as substrate by kinase-Glo assay
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 393.54, ALogP 4.34, HBA 5, HBD 3, PSA 106.92, QED 0.72
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](O)[C@@H]1O
InChIKey: AISMIGRIJQYZHW-NXTZNFLJSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of PIM3 (unknown origin) using Bad peptide NH2-AGAGRSRHSSYPAGT-OH as substrate measured after 10 mins in presence of ATP by luciferase-luciferin based Kinase-Glo luminescence assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 457.45, ALogP 4.05, HBA 5, HBD 3, PSA 95.34, QED 0.55
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC(Cc1ccccc1)C21COC1
InChIKey: STMXAUVFLJMWDN-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 414.47, ALogP 2.7, HBA 7, HBD 1, PSA 91.85, QED 0.71
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(Cl)cn3)cc2[C@@]2(COC(N)=N2)C12COC2
InChIKey: INWIVMOTHPFWNU-NRFANRHFSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 428.88, ALogP 2.72, HBA 7, HBD 2, PSA 108.06, QED 0.76
Compound (SMILES): Cc1[nH]nc2c1C(c1ccc(Cl)cc1)N(c1cc(C)c(=O)n(C)c1)C2=O
InChIKey: GXKIVKDALCGWBS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 368.82, ALogP 3.13, HBA 4, HBD 1, PSA 70.99, QED 0.76
Compound (SMILES): Cn1cc(N2C(=O)c3nn(C4CC4)cc3C2c2ccc(Cl)cc2)cc(Cl)c1=O
InChIKey: RQSRLTLIMDDPDM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 415.28, ALogP 3.97, HBA 5, HBD 0, PSA 60.13, QED 0.65
Compound (SMILES): COc1ncc(-n2nc3c(c2C)C(c2ccc(Cl)cc2)N(c2cc(Cl)c(=O)n(C)c2)C3=O)c(OC)n1
InChIKey: IBJLUHJBIGMOMD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 527.37, ALogP 3.74, HBA 9, HBD 0, PSA 104.37, QED 0.39
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin)
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@@H]1O
InChIKey: HIRGJKYVLHTQTI-NBDAELCASA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 456.47, ALogP 4.01, HBA 5, HBD 3, PSA 101.13, QED 0.55
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3ccccc3F)n2)C1
InChIKey: ATNCLUHEGCYVPT-XHSDSOJGSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 422.48, ALogP 4.91, HBA 4, HBD 2, PSA 80.9, QED 0.63
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of PIM2 kinase (unknown origin) using Biotin-AGAGRSRHSSYPAGT-OH as substrate after 2 hrs by alphascreen assay
Measurement: Ki = 0.018 nM (pChEMBL 10.739999771118164)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](O)[C@@H]1O
InChIKey: AISMIGRIJQYZHW-NXTZNFLJSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 457.45, ALogP 4.05, HBA 5, HBD 3, PSA 95.34, QED 0.55
Compound (SMILES): Cn1cc(N2C(=O)c3nn(C4CC4)cc3C2c2ccc(Cl)cc2)cc(Cl)c1=O
InChIKey: RQSRLTLIMDDPDM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 415.28, ALogP 3.97, HBA 5, HBD 0, PSA 60.13, QED 0.65
Compound (SMILES): COc1ncc(-n2nc3c(c2C)C(c2ccc(Cl)cc2)N(c2cc(Cl)c(=O)n(C)c2)C3=O)c(OC)n1
InChIKey: IBJLUHJBIGMOMD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: TR-FRET In-Vitro Binding Assay: All assays were performed in 384-well microtiter plates. Each assay plate contained 8-point serial dilutions for 40 test compounds, plus 16 high- and 16 low controls. Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Perkin Elmer/Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO HummingBird nanodispenser (Zinsser Analytic). The assay was started by stepwise addition of 4.5 uL per well of bromo domain protein (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 45 nM His-Brd2(60-472) or 45 nM His-Brd3(20-477) or 45 nM His-Brd4(44-477) all proteins produced in-house) and 4.5 uL per well of peptide solution (50 mM HEPES, pH 7.5, 0.005% Tween20, 0.1% BSA, 50 mM NaCl, 60 nM acetyl-histone H4 (AcK 5, 8, 12, 16) (Biosyntan GmbH)). Reactions were incubated at 30 C. for 35 minutes.
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 527.37, ALogP 3.74, HBA 9, HBD 0, PSA 104.37, QED 0.39
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL (unknown origin)
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT (unknown origin)
Measurement: IC50 = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin)
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q13554
Assay: Inhibition of CAMK2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6
Compound (SMILES): Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(C)[nH]nc3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: AFTBNZZMNUUEFO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 591.78, ALogP 6.24, HBA 9, HBD 3, PSA 125.13, QED 0.21
Compound (SMILES): C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
InChIKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1/cyclin B (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.47, ALogP 5.04, HBA 4, HBD 2, PSA 80.9, QED 0.6