lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H]1NCCC1=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)NCC(N)=O
InChIKey: WEEHADTZCAHCEM-KQXFHTIYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]-His5, D-Tyr6]GnRH from mutant GnRHR, GnRHR S203P
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 1182.31
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H]1NCCC1=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)NCC(N)=O
InChIKey: WEEHADTZCAHCEM-KQXFHTIYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]-His5, D-Tyr6]GnRH from human wild type GnRHR
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 1182.31
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of C-terminal ploy-His-tagged human PI3Kgamma expressed in baculovirus-infected sf9 cells using PI(4,5)P2 as substrate after 15 mins by HTRF assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): COc1cccc(OC)c1C1CCCC(=O)N1Cc1ccc2ccccc2n1
InChIKey: ADMREWYBXXZUMI-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: In Vitro Assay: Intracellular Calcium Measurements : In Vitro Assay: Intracellular Calcium Measurements:Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 g/ml G418, 100 U/ml penicillin, 100 g/ml streptomycin and 10% heat inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into 384-well black clear bottom sterile plates (Greiner). The seeded plates are incubated overnight at 37° C. in 5% CO2. Human orexin-A as an agonist is prepared as 1 mM stock solution in MeOH:water (1:1), diluted in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES for use in the assay at a final concentration of 3 nM.Antagonists are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates using DMSO followed by a transfer of the dilutions into in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES. On the day of the assay, 50 μl of staining buffer (HBSS containing 1% FCS, 20 mM HEPES, NaHCO3: 0.375 g/l, 5 mM probenecid (Sigma) and 3 M of the fluorescent calcium indicator fluo-4 AM (1 mM stock solution in DMSO, containing 10% pluronic) is added to each well. The 384-well cell-plates are incubated for 50 min at 37° C. in 5% CO2 followed by equilibration at RT for 30 min before measurement.
Measurement: IC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 376.46, ALogP 4.51, HBA 4, HBD 0, PSA 51.66, QED 0.66
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal ploy-His-tagged human PI3Kdelta expressed in baculovirus-infected sf9 cells using PI(4,5)P2 as substrate after 15 mins by HTRF assay
Measurement: IC50 = 468 nM (pChEMBL 6.329999923706055)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): COc1cccc(OC)c1C1CCCC(=O)N1Cc1ccc2ccccc2n1
InChIKey: ADMREWYBXXZUMI-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: In Vitro Assay: Intracellular Calcium Measurements : In Vitro Assay: Intracellular Calcium Measurements:Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 g/ml G418, 100 U/ml penicillin, 100 g/ml streptomycin and 10% heat inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into 384-well black clear bottom sterile plates (Greiner). The seeded plates are incubated overnight at 37° C. in 5% CO2. Human orexin-A as an agonist is prepared as 1 mM stock solution in MeOH:water (1:1), diluted in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES for use in the assay at a final concentration of 3 nM.Antagonists are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates using DMSO followed by a transfer of the dilutions into in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES. On the day of the assay, 50 μl of staining buffer (HBSS containing 1% FCS, 20 mM HEPES, NaHCO3: 0.375 g/l, 5 mM probenecid (Sigma) and 3 M of the fluorescent calcium indicator fluo-4 AM (1 mM stock solution in DMSO, containing 10% pluronic) is added to each well. The 384-well cell-plates are incubated for 50 min at 37° C. in 5% CO2 followed by equilibration at RT for 30 min before measurement.
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 376.46, ALogP 4.51, HBA 4, HBD 0, PSA 51.66, QED 0.66
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal ploy-His-tagged human PI3Kbeta expressed in baculovirus-infected sf21 cells using PI(4,5)P2 as substrate after 15 mins by HTRF assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of N-terminal ploy-His-tagged human PI3Kalpha expressed in baculovirus-infected sf9 cells using PI(4,5)P2 as substrate after 15 mins by HTRF assay
Measurement: IC50 = 1539 nM (pChEMBL 5.809999942779541)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Sandwich Immunoassay: This test is based on measurement of the expression of AKT protein phosphorylated on serine 473 (P-AKT-S473) in the PC3 human prostate carcinoma line, by the technique based on a sandwich immunoassay using the Kit MSD Multi-spot Biomarker Detection of Meso Scale Discovery: phospho-Akt kits (Ser473) whole cell lysate (# K151 CAD) or phospho-Akt (Ser473) / Akt whole cell lysate Total (# K15100D). The primary antibody specific for P-AKT-S473 (Kit # K151 CAD) is coated onto an electrode in each well of 96-well plates of the MSD kit: after adding a protein lysate in each well, the revelation of the signal done by the addition of a secondary antibody labeled with an electrochemiluminescent detection compound. The procedure is described in the kit.On day 1, the PC3 cells are inoculated in 96-well plates (TPP # 92096) at a concentration of 35000 cells / well in 200 uL DMEM medium (DMEM Gibco # 1 1960-044) containing 10% fetal calf serum (FBS Gibco, # 10500-056) and 1% glutamine.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Sandwich Immunoassay: This test is based on measurement of the expression of AKT protein phosphorylated on serine 473 (P-AKT-S473) in the PC3 human prostate carcinoma line, by the technique based on a sandwich immunoassay using the Kit MSD Multi-spot Biomarker Detection of Meso Scale Discovery: phospho-Akt kits (Ser473) whole cell lysate (# K151 CAD) or phospho-Akt (Ser473) / Akt whole cell lysate Total (# K15100D). The primary antibody specific for P-AKT-S473 (Kit # K151 CAD) is coated onto an electrode in each well of 96-well plates of the MSD kit: after adding a protein lysate in each well, the revelation of the signal done by the addition of a secondary antibody labeled with an electrochemiluminescent detection compound. The procedure is described in the kit.On day 1, the PC3 cells are inoculated in 96-well plates (TPP # 92096) at a concentration of 35000 cells / well in 200 uL DMEM medium (DMEM Gibco # 1 1960-044) containing 10% fetal calf serum (FBS Gibco, # 10500-056) and 1% glutamine.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
InChIKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibitory Assay: This test is based on measuring the expression of the AKT protein phosphorylated on serine 473 (P-AKT-S473), in the PC3 human prostate carcinoma line, by means of the technique based on a sandwich immunoassay using the MSD Multi-spot Biomarker Detection kit from Meso Scale Discovery: phospho-Akt (Ser473) whole cell lysate kit (#K151CAD) or phospho-Akt (Ser473)/Total Akt whole cell lysate kit (#K15100D). The primary antibody specific for P-AKT-S473 (Kit #K151CAD) is coated on to an electrode in each well of the 96-well plates of the MSD, kit: after the addition of a protein lysate to each well, the signal is visualised by adding a secondary detection antibody labelled with an electrochemoluminescent compound. The procedure followed is that described in the kit.On day 1, the PC3 cells are seeded into 96-well plates (TPP, #92096) at the concentration of 35 000 cells/well in 200 ul of DMEM medium (DMEM Gibco #11960-044) containing 10% of foetal calf serum (FCS Gibco, #10500-056).
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 354.41, ALogP 1.13, HBA 5, HBD 1, PSA 78.53, QED 0.89
Compound (SMILES): COc1cc(N2CCOCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ILSYFQQNAQIMBK-BBNYVJOESA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 494.98, ALogP 3.21, HBA 7, HBD 3, PSA 118.39, QED 0.45
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: MZGDIKYASHMRSG-UGCQDJOBSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human pooled liver microsomes using S-mephenytoin as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 508.03, ALogP 3.13, HBA 7, HBD 3, PSA 112.4, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCOCC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ADYZVNMLQOHYDE-BAYWULLTSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human pooled liver microsomes using S-mephenytoin as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 578.12, ALogP 3.68, HBA 8, HBD 3, PSA 121.63, QED 0.36
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ORFGUEWOGJKLFU-XOSANVASSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human pooled liver microsomes using S-mephenytoin as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.16, ALogP 3.59, HBA 8, HBD 3, PSA 115.64, QED 0.36
Compound (SMILES): COc1cc(CN2CCOCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: QXOZRBMOILEYGU-QMKUDKLTSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 509.01, ALogP 3.21, HBA 7, HBD 3, PSA 118.39, QED 0.42
Compound (SMILES): COc1cc(CN2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: CAIAMTHZGVFCNA-XKPGHWPRSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 522.05, ALogP 3.12, HBA 7, HBD 3, PSA 112.4, QED 0.41
Compound (SMILES): O=C(O)c1ccc(-c2nn(C(=O)c3c(Cl)cccc3Cl)c3ccccc23)cc1
InChIKey: YRLYJWZLPGDXGP-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GST-tagged RORgammat LBD (unknown origin) using fluorescein-D22 co-activator peptide as substrate incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 411.24, ALogP 5.4, HBA 4, HBD 1, PSA 72.19, QED 0.49
Compound (SMILES): COc1ccc(-c2csc(-c3cccc(NC(=O)C4CC4)c3)n2)cc1
InChIKey: MUSGQAWBFRVLPG-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 350.44, ALogP 4.83, HBA 4, HBD 1, PSA 51.22, QED 0.72
Compound (SMILES): O=C(Nc1cccc(-c2csc(-c3ccccc3)n2)c1)c1ccco1
InChIKey: PUHVOLNAUUHQEW-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 346.41, ALogP 5.32, HBA 4, HBD 1, PSA 55.13, QED 0.54
Compound (SMILES): CCOc1ccc(-c2nc(-c3ccc4[nH]c(=O)[nH]c4c3)cs2)cc1
InChIKey: JLXIQNXVICPWCG-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 17900 nM (pChEMBL 4.75)
Descriptors: MW 337.4, ALogP 4.05, HBA 4, HBD 2, PSA 70.77, QED 0.59
Compound (SMILES): COc1ccccc1-c1nc(-c2ccc3c(c2)CCN3S(C)(=O)=O)cs1
InChIKey: LPLOMJOCYXZEFN-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 31300 nM (pChEMBL 4.5)
Descriptors: MW 386.5, ALogP 3.81, HBA 5, HBD 0, PSA 59.5, QED 0.68
Compound (SMILES): COc1ccc(-c2nc(-c3ccc4c(c3)CCN4S(C)(=O)=O)cs2)cc1
InChIKey: SALSUOXOFMKBBM-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 26100 nM (pChEMBL 4.579999923706055)
Descriptors: MW 386.5, ALogP 3.81, HBA 5, HBD 0, PSA 59.5, QED 0.68
Compound (SMILES): Cc1cccc(-c2nc(-c3ccc4c(c3)CCN4S(C)(=O)=O)cs2)c1
InChIKey: QCCDZNXSEKJZRH-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 34400 nM (pChEMBL 4.460000038146973)
Descriptors: MW 370.5, ALogP 4.11, HBA 4, HBD 0, PSA 50.27, QED 0.7
Compound (SMILES): COc1ccc(-c2nc(-c3cc(C)n(CC4CCCO4)c3C)cs2)cc1
InChIKey: HVFAJKDLBAWLHG-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 368.5, ALogP 5.08, HBA 5, HBD 0, PSA 36.28, QED 0.63
Compound (SMILES): CCOc1ccc(-c2nc(-c3ccc4c(c3)CC(=O)N4C)cs2)cc1
InChIKey: UXFRVZIEPXHVOI-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 350.44, ALogP 4.39, HBA 4, HBD 0, PSA 42.43, QED 0.7
Compound (SMILES): CCOc1ccc(-c2nc(-c3ccc4ccccc4c3)cs2)cc1
InChIKey: JRAWQXYLJRIVTB-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of Cdc25B (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 331.44, ALogP 6.03, HBA 3, HBD 0, PSA 22.12, QED 0.46
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Plate-Based Time-Resolved Fluorescence Energy Transfer (TR-FRET) Assays: Determine the binding ability of BRD4 compounds to bromodomains of BRD2 and BRD4. 96 well plate based commercial TR-FRET Assay kits (Cayman Chemical, Ann Arbor, Mich.) were used to determine the binding ability of tested BRD4 inhibitors to the BRD4 bromodomains (BD) using the two recombinant BRD4 BDs using time-resolved fluorescence energy transfer (TR-FRET) assays. A series concentrations of BRD4 inhibitors from 0.01 nM to 100 ��M for 24 hours and were added into 96 well test plate and mixed with other reaction components based on the instructions from vendor followed by incubation 1 h at room temperature. The commercially available BRD inhibitor JQ1 was used as the positive control. The plate were read in time-resolved format by exciting the sample at 340 nm and reading emissions at 620 and 670 nm, using a 100 ��s delay and a 500 ��s window at a Tecan M1000 pro reader. A plot of the TR-FRET ratio (670 nm emission/620 nm emission0 versus inhibitor concentration on semi-log axes results in a sigmoidal dose-response curve typical of competitive assays.
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1nc2c(o1)CC(CN1CCC(c3c[nH]c4cc(F)ccc34)CC1)CC2=O
InChIKey: RXIUGRLQOGTTNP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human cloned 5-HT6 receptor expressed in HEK293 cell membrane after 60 mins by liquid scintillation counting analysis
Measurement: Ki = 213.8 nM (pChEMBL 6.670000076293945)
Descriptors: MW 381.45, ALogP 4.23, HBA 4, HBD 1, PSA 62.13, QED 0.74
Compound (SMILES): O=C1CC(CN2CCC(c3c[nH]c4cc(F)ccc34)CC2)Cc2nc(N3CCCC3)sc21
InChIKey: GYWXJONOYHIRDG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human cloned 5-HT6 receptor expressed in HEK293 cell membrane after 60 mins by liquid scintillation counting analysis
Measurement: Ki = 354.81 nM (pChEMBL 6.449999809265137)
Descriptors: MW 452.6, ALogP 4.99, HBA 5, HBD 1, PSA 52.23, QED 0.61
Compound (SMILES): CSc1nc(N2C[C@@H]3[C@H](C2)[C@H]3C(=O)O)ccc1C(=O)NC12CC3CC(CC(C3)C1)C2
InChIKey: MATQWNLSVRLACV-VUGDMWQRSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P37058
Assay: Inhibition of recombinant 17beta-HSD3 (unknown origin) assessed as conversion of androstenedione to testosterone after 90 mins by scintillation counting analysis
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 427.57, ALogP 3.27, HBA 5, HBD 2, PSA 82.53, QED 0.7
Compound (SMILES): COc1cc(N2CCOCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ILSYFQQNAQIMBK-BBNYVJOESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate by LC/MS/MS analysis
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 494.98, ALogP 3.21, HBA 7, HBD 3, PSA 118.39, QED 0.45
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: MZGDIKYASHMRSG-UGCQDJOBSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 508.03, ALogP 3.13, HBA 7, HBD 3, PSA 112.4, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCOCC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ADYZVNMLQOHYDE-BAYWULLTSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 578.12, ALogP 3.68, HBA 8, HBD 3, PSA 121.63, QED 0.36
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ORFGUEWOGJKLFU-XOSANVASSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.16, ALogP 3.59, HBA 8, HBD 3, PSA 115.64, QED 0.36
Compound (SMILES): COc1cc(CN2CCOCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: QXOZRBMOILEYGU-QMKUDKLTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 509.01, ALogP 3.21, HBA 7, HBD 3, PSA 118.39, QED 0.42
Compound (SMILES): COc1cc(CN2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: CAIAMTHZGVFCNA-XKPGHWPRSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 522.05, ALogP 3.12, HBA 7, HBD 3, PSA 112.4, QED 0.41
Compound (SMILES): O=C(O)c1ccc(-c2nn(C(=O)c3c(Cl)cccc3Cl)c3ccccc23)cc1
InChIKey: YRLYJWZLPGDXGP-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Transactivation of recombinant GAL4-DBD fused RORgammat LBD (unknown origin) expressed in HEK293T cells incubated for 18 to 24 hrs by dual-Glo luciferase assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 411.24, ALogP 5.4, HBA 4, HBD 1, PSA 72.19, QED 0.49
Compound (SMILES): COc1ccc(-c2csc(-c3cccc(NC(=O)C4CC4)c3)n2)cc1
InChIKey: MUSGQAWBFRVLPG-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 350.44, ALogP 4.83, HBA 4, HBD 1, PSA 51.22, QED 0.72
Compound (SMILES): O=C(Nc1cccc(-c2csc(-c3ccccc3)n2)c1)c1ccco1
InChIKey: PUHVOLNAUUHQEW-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 346.41, ALogP 5.32, HBA 4, HBD 1, PSA 55.13, QED 0.54
Compound (SMILES): CCOc1ccc(-c2nc(-c3ccc4[nH]c(=O)[nH]c4c3)cs2)cc1
InChIKey: JLXIQNXVICPWCG-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 337.4, ALogP 4.05, HBA 4, HBD 2, PSA 70.77, QED 0.59
Compound (SMILES): COc1ccccc1-c1nc(-c2ccc3c(c2)CCN3S(C)(=O)=O)cs1
InChIKey: LPLOMJOCYXZEFN-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 41700 nM (pChEMBL 4.380000114440918)
Descriptors: MW 386.5, ALogP 3.81, HBA 5, HBD 0, PSA 59.5, QED 0.68
Compound (SMILES): COc1ccc(-c2nc(-c3ccc4c(c3)CCN4S(C)(=O)=O)cs2)cc1
InChIKey: SALSUOXOFMKBBM-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 42900 nM (pChEMBL 4.369999885559082)
Descriptors: MW 386.5, ALogP 3.81, HBA 5, HBD 0, PSA 59.5, QED 0.68
Compound (SMILES): Cc1cccc(-c2nc(-c3ccc4c(c3)CCN4S(C)(=O)=O)cs2)c1
InChIKey: QCCDZNXSEKJZRH-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 31800 nM (pChEMBL 4.5)
Descriptors: MW 370.5, ALogP 4.11, HBA 4, HBD 0, PSA 50.27, QED 0.7
Compound (SMILES): COc1ccc(-c2nc(-c3cc(C)n(CC4CCCO4)c3C)cs2)cc1
InChIKey: HVFAJKDLBAWLHG-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 31100 nM (pChEMBL 4.510000228881836)
Descriptors: MW 368.5, ALogP 5.08, HBA 5, HBD 0, PSA 36.28, QED 0.63
Compound (SMILES): CCOc1ccc(-c2nc(-c3ccc4c(c3)CC(=O)N4C)cs2)cc1
InChIKey: UXFRVZIEPXHVOI-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 33600 nM (pChEMBL 4.46999979019165)
Descriptors: MW 350.44, ALogP 4.39, HBA 4, HBD 0, PSA 42.43, QED 0.7
Compound (SMILES): CCOc1ccc(-c2nc(-c3ccc4ccccc4c3)cs2)cc1
InChIKey: JRAWQXYLJRIVTB-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of Cdc25A (unknown origin) phosphatase activity assessed as fluorescence by BMG plate reader in the presence of 0.005% Tween-20
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 331.44, ALogP 6.03, HBA 3, HBD 0, PSA 22.12, QED 0.46
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Plate-Based Time-Resolved Fluorescence Energy Transfer (TR-FRET) Assays: Determine the binding ability of BRD4 compounds to bromodomains of BRD2 and BRD4. 96 well plate based commercial TR-FRET Assay kits (Cayman Chemical, Ann Arbor, Mich.) were used to determine the binding ability of tested BRD4 inhibitors to the BRD4 bromodomains (BD) using the two recombinant BRD4 BDs using time-resolved fluorescence energy transfer (TR-FRET) assays. A series concentrations of BRD4 inhibitors from 0.01 nM to 100 ��M for 24 hours and were added into 96 well test plate and mixed with other reaction components based on the instructions from vendor followed by incubation 1 h at room temperature. The commercially available BRD inhibitor JQ1 was used as the positive control. The plate were read in time-resolved format by exciting the sample at 340 nm and reading emissions at 620 and 670 nm, using a 100 ��s delay and a 500 ��s window at a Tecan M1000 pro reader. A plot of the TR-FRET ratio (670 nm emission/620 nm emission0 versus inhibitor concentration on semi-log axes results in a sigmoidal dose-response curve typical of competitive assays.
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): CSc1nc(N2C[C@@H]3[C@H](C2)[C@H]3C(=O)O)ccc1C(=O)NC12CC3CC(CC(C3)C1)C2
InChIKey: MATQWNLSVRLACV-VUGDMWQRSA-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 427.57, ALogP 3.27, HBA 5, HBD 2, PSA 82.53, QED 0.7
Compound (SMILES): COc1cc(N2CCOCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ILSYFQQNAQIMBK-BBNYVJOESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using midazolam as substrate by LC/MS/MS analysis
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 494.98, ALogP 3.21, HBA 7, HBD 3, PSA 118.39, QED 0.45
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: MZGDIKYASHMRSG-UGCQDJOBSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate by LC/MS/MS analysis
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 508.03, ALogP 3.13, HBA 7, HBD 3, PSA 112.4, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCOCC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ADYZVNMLQOHYDE-BAYWULLTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 578.12, ALogP 3.68, HBA 8, HBD 3, PSA 121.63, QED 0.36
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ORFGUEWOGJKLFU-XOSANVASSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.16, ALogP 3.59, HBA 8, HBD 3, PSA 115.64, QED 0.36
Compound (SMILES): COc1cc(CN2CCOCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: QXOZRBMOILEYGU-QMKUDKLTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using midazolam as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 509.01, ALogP 3.21, HBA 7, HBD 3, PSA 118.39, QED 0.42
Compound (SMILES): COc1cc(CN2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: CAIAMTHZGVFCNA-XKPGHWPRSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using midazolam as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 522.05, ALogP 3.12, HBA 7, HBD 3, PSA 112.4, QED 0.41
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Plate-Based Time-Resolved Fluorescence Energy Transfer (TR-FRET) Assays: Determine the binding ability of BRD4 compounds to bromodomains of BRD2 and BRD4. 96 well plate based commercial TR-FRET Assay kits (Cayman Chemical, Ann Arbor, Mich.) were used to determine the binding ability of tested BRD4 inhibitors to the BRD4 bromodomains (BD) using the two recombinant BRD4 BDs using time-resolved fluorescence energy transfer (TR-FRET) assays. A series concentrations of BRD4 inhibitors from 0.01 nM to 100 ��M for 24 hours and were added into 96 well test plate and mixed with other reaction components based on the instructions from vendor followed by incubation 1 h at room temperature. The commercially available BRD inhibitor JQ1 was used as the positive control. The plate were read in time-resolved format by exciting the sample at 340 nm and reading emissions at 620 and 670 nm, using a 100 ��s delay and a 500 ��s window at a Tecan M1000 pro reader. A plot of the TR-FRET ratio (670 nm emission/620 nm emission0 versus inhibitor concentration on semi-log axes results in a sigmoidal dose-response curve typical of competitive assays.
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: MZGDIKYASHMRSG-UGCQDJOBSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using midazolam as substrate by LC/MS/MS analysis
Measurement: IC50 = 13700 nM (pChEMBL 4.860000133514404)
Descriptors: MW 508.03, ALogP 3.13, HBA 7, HBD 3, PSA 112.4, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCOCC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ADYZVNMLQOHYDE-BAYWULLTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using midazolam as substrate by LC/MS/MS analysis
Measurement: IC50 = 14200 nM (pChEMBL 4.849999904632568)
Descriptors: MW 578.12, ALogP 3.68, HBA 8, HBD 3, PSA 121.63, QED 0.36
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
InChIKey: ORFGUEWOGJKLFU-XOSANVASSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human pooled liver microsomes using midazolam as substrate by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.16, ALogP 3.59, HBA 8, HBD 3, PSA 115.64, QED 0.36
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Plate-Based Time-Resolved Fluorescence Energy Transfer (TR-FRET) Assays: Determine the binding ability of BRD4 compounds to bromodomains of BRD2 and BRD4. 96 well plate based commercial TR-FRET Assay kits (Cayman Chemical, Ann Arbor, Mich.) were used to determine the binding ability of tested BRD4 inhibitors to the BRD4 bromodomains (BD) using the two recombinant BRD4 BDs using time-resolved fluorescence energy transfer (TR-FRET) assays. A series concentrations of BRD4 inhibitors from 0.01 nM to 100 ��M for 24 hours and were added into 96 well test plate and mixed with other reaction components based on the instructions from vendor followed by incubation 1 h at room temperature. The commercially available BRD inhibitor JQ1 was used as the positive control. The plate were read in time-resolved format by exciting the sample at 340 nm and reading emissions at 620 and 670 nm, using a 100 ��s delay and a 500 ��s window at a Tecan M1000 pro reader. A plot of the TR-FRET ratio (670 nm emission/620 nm emission0 versus inhibitor concentration on semi-log axes results in a sigmoidal dose-response curve typical of competitive assays.
Measurement: IC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Plate-Based Time-Resolved Fluorescence Energy Transfer (TR-FRET) Assays: Determine the binding ability of BRD4 compounds to bromodomains of BRD2 and BRD4. 96 well plate based commercial TR-FRET Assay kits (Cayman Chemical, Ann Arbor, Mich.) were used to determine the binding ability of tested BRD4 inhibitors to the BRD4 bromodomains (BD) using the two recombinant BRD4 BDs using time-resolved fluorescence energy transfer (TR-FRET) assays. A series concentrations of BRD4 inhibitors from 0.01 nM to 100 ��M for 24 hours and were added into 96 well test plate and mixed with other reaction components based on the instructions from vendor followed by incubation 1 h at room temperature. The commercially available BRD inhibitor JQ1 was used as the positive control. The plate were read in time-resolved format by exciting the sample at 340 nm and reading emissions at 620 and 670 nm, using a 100 ��s delay and a 500 ��s window at a Tecan M1000 pro reader. A plot of the TR-FRET ratio (670 nm emission/620 nm emission0 versus inhibitor concentration on semi-log axes results in a sigmoidal dose-response curve typical of competitive assays.
Measurement: IC50 = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Plate-Based Time-Resolved Fluorescence Energy Transfer (TR-FRET) Assays: Determine the binding ability of BRD4 compounds to bromodomains of BRD2 and BRD4. 96 well plate based commercial TR-FRET Assay kits (Cayman Chemical, Ann Arbor, Mich.) were used to determine the binding ability of tested BRD4 inhibitors to the BRD4 bromodomains (BD) using the two recombinant BRD4 BDs using time-resolved fluorescence energy transfer (TR-FRET) assays. A series concentrations of BRD4 inhibitors from 0.01 nM to 100 ��M for 24 hours and were added into 96 well test plate and mixed with other reaction components based on the instructions from vendor followed by incubation 1 h at room temperature. The commercially available BRD inhibitor JQ1 was used as the positive control. The plate were read in time-resolved format by exciting the sample at 340 nm and reading emissions at 620 and 670 nm, using a 100 ��s delay and a 500 ��s window at a Tecan M1000 pro reader. A plot of the TR-FRET ratio (670 nm emission/620 nm emission0 versus inhibitor concentration on semi-log axes results in a sigmoidal dose-response curve typical of competitive assays.
Measurement: IC50 = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: ATPLITE assay: Acetyl-Histone Binding Assay. Assays were performed as described previously with minor modifications from the manufacturer's protocol (PerkinElmer, USA). All reagents were diluted in 50 mM HEPES, 100 mM NaCl, 0.1% BSA, pH 7.4 supplemented with 0.05% CHAPS and allowed to equilibrate to room temperature prior to addition to plates. A 24-point 1:2 serial dilution of the ligands was prepared over the range of 150-0 μM and 4 μl transferred to low-volume 384-well plates (ProxiPlate-384 Plus, PerkinElmer, USA), followed by 4 μl of HIS-tagged protein (BRD4/1, 250 nM, BRD4/2 and CREBBP, 2000 nM). Plates were scaled and incubated at room temperature for 30 minutes, before the addition of 4 μl of biotinylated peptide at equimolar concentration to the protein [peptide for BRD4(1) & BRD4(2), and BRDT: H4K5acK8acK12acK16ac, H-SGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH; peptide for CREBBP: H3K36ac, Biotin-KSAPATGGVK(Ac)KPHRYRPGT-OH (Cambridge Research Biochemicals, UK)]. Plates were sealed and incubated for a further 30 minutes, before the addition of 4 μl of streptavidin-coated donor beads (25 μg/ml) and 4 μl nickel chelate acceptor beads (25 μg/ml) under low light conditions. Plates were foil-sealed to protect from light, incubated at room temperature for 60 minutes and read on a PHERAstar FS plate reader (BMG Labtech, Germany) using an AlphaScreen 680 excitation/570 emission filter set. IC50 values were calculated in Prism 5 (GraphPad Software, USA) after normalization against corresponding DMSO controls and are given as the final concentration of compound in the 20 μl reaction volume.
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Acetyl-Histone Binding Assay: Assays were performed as described previously with minor modifications from the manufacturer's protocol (PerkinElmer, USA). All reagents were diluted in 50 mM HEPES, 100 mM NaCl, 0.1% BSA, pH 7.4 supplemented with 0.05% CHAPS and allowed to equilibrate to room temperature prior to addition to plates. A 24-point 1:2 serial dilution of the ligands was prepared over the range of 150-0 μM and 4 μl transferred to low-volume 384-well plates (PROXIPLATE-384 Plus, PerkinElmer, USA), followed by 4 μl of HIS-tagged protein (BRD4/1, 250 nM, BRD4/2 and CREBBP, 2000 nM). Plates were sealed and incubated at room temperature for 30 minutes, before the addition of 4 μl of biotinylated peptide at equimolar concentration to the protein [peptide for BRD4(1) & BRD4(2), and BRDT: H4K5acK8acK12acK16ac, H-SGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH; peptide for CREBBP: H3K36ac, Biotin-KSAPATGGVK(Ac)KPHRYRPGT-OH (Cambridge Research Biochemicals, UK)]. Plates were sealed and incubated for a further 30 minutes, before the addition of 4 μl of streptavidin-coated donor beads (25 μg/ml) and 4 μl nickel chelate acceptor beads (25 μg/ml) under low light conditions. Plates were foil-sealed to protect from light, incubated at room temperature for 60 minutes and read on a PHERASTAR FS plate reader (BMG Labtech, Germany) using an ALPHASCREEN 680 excitation/570 emission filter set. IC50 values were calculated in Prism 5 (GRAPHPAD Software, USA) after normalization against corresponding DMSO controls and are given as the final concentration of compound in the 20 μl reaction volume.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Affinity Phenotypic Cellular interaction: (Cell Proliferation (Cell TiterGlo assay Promega in NMC 11060 cells)) EUB0000200b BRD2
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Affinity Phenotypic Cellular interaction: (Cell Proliferation (Cell TiterGlo assay Promega in NMC 11060 cells)) EUB0000200b BRD3
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Affinity Phenotypic Cellular interaction: (Cell Proliferation (Cell TiterGlo assay Promega in NMC 11060 cells)) EUB0000200b BRD4
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Affinity Phenotypic Cellular interaction: (Cell Proliferation (Cell TiterGlo assay Promega in NMC 11060 cells)) EUB0000200b BRDT
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Affinity Biochemical interaction: (Luminescence proximity homogeneous assay (alpha-screen, measuring binding of a tetra-acetylated histone H4 peptide to BRD4)) EUB0000200b BRD4
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Isothermal Titration Calorimetry Analysis of Binding to Brd2-BD1 and Brd2-BD2: Binding of compounds to BRD2 was monitored using an ITC200 (Microcal, Piscataway, N.J.). Either Brd2.1 (74-194) or Brd2.2 (348-455) was dialyzed overnight into a solution containing 50 mM HEPES, pH 7.0 and 150 mM NaCl at 15° C. Enzyme concentrations were determined after dialysis by absorbance at 280 nm using a molar extinction coefficient (ε280) of 25,565 M−1 cm−1 (2.1) or 16,055 M−1 cm−1 (2.2). Enzyme was diluted in dialysis buffer and 39.6 μL was loaded into the syringe. Compounds were dissolved in the same dialysis buffer and loaded in the cell to a volume of 204 μL. Injections were carried out by serial injections of enzyme; first, 1 injection of 1 μL, followed by 19 incremental injections of 2 μL, at 120 second intervals. Data from the first injection was excluded, due to pre-equilibration mixing between the contents of cell and syringe at the syringe tip. Peak areas were integrated, normalized, and then fitted by non-linear regression using the independent sites model in Origin (version 2.3.6, Microcal, Piscataway, N.J.).
Measurement: Kd = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 457, ALogP 5.53, HBA 7, HBD 0, PSA 69.37, QED 0.49