lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc(-c4ccnn4C4CCCN(C(C)C)C4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: WGRUESGNZJBCSB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 < 0.035 nM (pChEMBL 10.456000328063965)
Descriptors: MW 518.64, ALogP 5.14, HBA 9, HBD 0, PSA 78.82, QED 0.36
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC4C4CCCCN4C)cc2OCC3)n(C(C)C)n1
InChIKey: GJMLYTYJDSCMCR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 475.64, ALogP 4.54, HBA 8, HBD 0, PSA 64.24, QED 0.55
Compound (SMILES): CCN(CC)C1CCOC(c2c(-c3ccc4c(c3)OCCn3cc(-c5nc(C)nn5C(C)C)nc3-4)cnn2C)C1
InChIKey: JUCFCEMDRWPMSZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 1.07 nM (pChEMBL 8.970000267028809)
Descriptors: MW 544.7, ALogP 5.05, HBA 10, HBD 0, PSA 88.05, QED 0.32
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C)c4C4CC(N(C)C(C)C)CCO4)cc2OCC3)n(C(C)C)n1
InChIKey: VVYWQZGWGMFFKQ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.939 nM (pChEMBL 9.029999732971191)
Descriptors: MW 544.7, ALogP 5.05, HBA 10, HBD 0, PSA 88.05, QED 0.34
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC4CN(C)C)cc2OCC3)n(C(C)C)n1
InChIKey: YHKYKDYCSFGCNF-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.445 nM (pChEMBL 9.350000381469727)
Descriptors: MW 435.58, ALogP 3.62, HBA 8, HBD 0, PSA 64.24, QED 0.61
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc(-c4ccnn4C4CCCN(C5COC5)C4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: LDVKGACWPSEWJI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 532.62, ALogP 4.13, HBA 10, HBD 0, PSA 88.05, QED 0.38
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc(-c4ccnn4C4CCCN(C(C)(C)CO)C4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: PXQTVSUZVWYORU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.415 nM (pChEMBL 9.380000114440918)
Descriptors: MW 548.67, ALogP 4.5, HBA 10, HBD 1, PSA 99.05, QED 0.38
Compound (SMILES): COc1cc2c(cc1[C@@H](C)N1CCN(C(C)(C)C)CC1)-c1nc(-c3nc(C)nn3C(C)C)cn1CCO2
InChIKey: PGCKRQJTWQLDQT-LJQANCHMSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 507.68, ALogP 4.58, HBA 9, HBD 0, PSA 73.47, QED 0.5
Compound (SMILES): COc1cc2c(cc1[C@H](C)N1CCN(C(C)(C)C)CC1)-c1nc(-c3nc(C)nn3C(C)C)cn1CCO2
InChIKey: PGCKRQJTWQLDQT-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 507.68, ALogP 4.58, HBA 9, HBD 0, PSA 73.47, QED 0.5
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2cc(-c4cnn(C)c4C4CCCN(C(C)C)C4)c(F)cc2OCC3)n(C(C)C)n1
InChIKey: DBPAOJPBWIKHNC-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 532.67, ALogP 5.22, HBA 9, HBD 0, PSA 78.82, QED 0.35
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(-c4cn[nH]c4C4CCCN(C(C)C)C4)cc2OCC3)n(C(C)C)n1
InChIKey: PAECUBUJXZVOQS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: PI3K enzymatic activity was assayed by measuring the amount of product phosphatidylinositol 3,4,5-phosphate (PIP3) formed from substrate 4,5 phosphatidylinositol 4,5-phosphate (PIP2) using a fluorescence polarization displacement assay. The decrease in fluorescence polarization of a fluorescent PIP.sub.3 probe is measured as it is displaced from a PIP.sub.3-binding protein GRP-1 detector by PI3K-catalyzed product. Assays were conducted in 384-well black Proxiplates in the presence of 10 mM Tris (pH 7.5), 50 mM NaCl, 4 mM MgCl.sub.2, 5% glycerol, 25 .mu.M ATP, 10 .mu.M PIP.sub.2 (Echelon Biosciences), 0.05% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, 1 mM dithiothreitol, and 2% DMSO. The kinase reactions were initiated by the addition of 40 ng/mL p110.alpha./p85.alpha., 300 ng/mL p110.beta./p85.alpha., 40 ng/mL p110.gamma., or 40 ng/mL p110.delta./p85.alpha. (Upstate Group, Millipore; Dundee, UK), and 10 .mu.M PIP.sub.2 (Echelon Biosciences) to the wells.
Measurement: IC50 = 0.972 nM (pChEMBL 9.010000228881836)
Descriptors: MW 500.65, ALogP 5.07, HBA 8, HBD 1, PSA 89.68, QED 0.41
Compound (SMILES): C/C=C/CC(C)C(O)C1C(=O)NC(CC)C(=O)N(C)C(C)C(=O)N(CC)C(C(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(CC(C)C)C(=O)NC(C)C(=O)NC(C)C(=O)N(C)C(CC(C)C)C(=O)N(C)C(CC(C)C)C(=O)N(C)C(C(C)C)C(=O)N1C
InChIKey: OLROWHGDTNFZBH-PBBVDAKRSA-N
Target: Solute carrier organic anion transporter family member 1B3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPD5
Assay: In Vitro Uptake Transporter Assay: To assess the inhibition of the OAT1B1 and OAT1B3 uptake transporters, an in vitro uptake transporter assay from Solvo Biotechnology Inc. was used. Uptake experiments with Test Article (TA) at 0.068, 0.2, 0.62, 1.8, 5.5, 16.7 and 50 uM, were performed on CHO cells stably expressing human SLC transporters OATP1B1 and OATP1B3. Parental cell line CHO-K was used as negative control. Cells (1x105 in 200 ul 1:1 mixture of Dulbecco's Modified Eagle's Medium and Ham's F-12 DMEM (F-12, Lonza, N.J., US) supplemented with 5 mM sodium butyrate) were plated on standard 96-well tissue culture plates and incubated 24 hours before the experiment at 37 C. in an atmosphere of 5% CO2 and 95% air. Before experiments the medium was aspirated by vacuum suction, cells were washed with 2x100 ul of Krebs-Henseleit buffer pH 7.3 (prepared from Sigma chemicals, Sigma-Aldrich, St Louis, Mo.). Uptake experiments were carried out at 37 C. in 50 ul of Krebs-Henseleit buffer.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 1216.66
Compound (SMILES): CC(=O)CC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc2cc(O)cc(F)c2)C(=O)N2CCCC(N2)C(=O)O[C@H](/C(C)=C/C=C/C(=O)N2CCCCO2)C/C=C/C=C/[C@H](O)[C@H](C)[C@H]1O
InChIKey: CFLBTKFHBBDVKC-RROFBZPUSA-N
Target: Bile salt export pump (SINGLE PROTEIN), Homo sapiens
UniProt: O95342
Assay: Inhibition Assay: To assess the inhibition of the MRP2, MRP3 and BSEP efflux transporters, an in vitro vesicular transporter assay from Solvo Biotechnology Inc. was used. The Test Articles (TAs) (at 0.068, 0.2, 0.62, 1.8, 5.5, 16.7 and 50 uM) were incubated with efflux transporter membrane vesicles (Solvo Biotechnology Inc.) both in the absence and presence of 4 mM ATP to distinguish between transporter mediated uptake and passive diffusion of TA's into the vesicles. In the case of MRP2 and MRP3 transporters reactions were carried out in the presence of 2 mM glutathione. Reaction mixtures were preincubated for ten minutes at 37 C. Reactions were started by the addition of 25 ul of 12 mM MgATP (4 mM final concentration in assay) or assay buffer for background controls. Reactions were stopped by adding 200 ul of ice-cold washing buffer and immediately followed by filtration on glass fiber filters in a 96-well format (filter plate).
Measurement: IC50 = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 868.01, ALogP 3.02, HBA 12, HBD 6, PSA 224.14, QED 0.12
Compound (SMILES): CCC(=O)OCCNC(CC(C)C)C1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: XCAMEKYVLTTXGP-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 386.36, ALogP 5.37, HBA 3, HBD 1, PSA 38.33, QED 0.46
Compound (SMILES): CCOc1ccc(C2(C(CC(C)C)NCCOC(=O)CC)CCC2)cc1
InChIKey: GAWYDFHTJQSNCE-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 80.4 nM (pChEMBL 7.090000152587891)
Descriptors: MW 361.53, ALogP 4.46, HBA 4, HBD 1, PSA 47.56, QED 0.47
Compound (SMILES): CCOC(=O)NCCNC(CC(C)C)C1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: SBTIZQKJKFHNPY-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 401.38, ALogP 5.17, HBA 3, HBD 2, PSA 50.36, QED 0.56
Compound (SMILES): CCOC(=O)NCCNC(CC(C)C)C1(c2ccc(OCC)cc2)CCC1
InChIKey: BKVALIDOPGIDPZ-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 376.54, ALogP 4.26, HBA 4, HBD 2, PSA 59.59, QED 0.57
Compound (SMILES): CCCC(=O)NCCNC(CC(C)C)C1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: ZJFMMMXNSXCMOB-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 27.8 nM (pChEMBL 7.559999942779541)
Descriptors: MW 399.41, ALogP 5.34, HBA 2, HBD 2, PSA 41.13, QED 0.52
Compound (SMILES): CCCC(=O)NCCNC(CC(C)C)C1(c2ccc(OCC)cc2)CCC1
InChIKey: KESMMXPCOOCEDA-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 374.57, ALogP 4.43, HBA 3, HBD 2, PSA 50.36, QED 0.53
Compound (SMILES): CC(CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 371.35, ALogP 4.69, HBA 2, HBD 2, PSA 55.12, QED 0.59
Compound (SMILES): C[C@@H](CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-AWEZNQCLSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 371.35, ALogP 4.69, HBA 2, HBD 2, PSA 55.12, QED 0.59
Compound (SMILES): C[C@H](CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-CQSZACIVSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 3415 nM (pChEMBL 5.46999979019165)
Descriptors: MW 371.35, ALogP 4.69, HBA 2, HBD 2, PSA 55.12, QED 0.59
Compound (SMILES): CCOc1ccc(C2(CC(C)CCNCCCC(N)=O)CCC2)cc1
InChIKey: ZEFQZGJPKZZHJW-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 346.52, ALogP 3.78, HBA 3, HBD 2, PSA 64.35, QED 0.57
Compound (SMILES): CCOc1ccc(C2(C[C@@H](C)CCNCCCC(N)=O)CCC2)cc1
InChIKey: ZEFQZGJPKZZHJW-KRWDZBQOSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Radioligand Binding Assay: The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275 (6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 2.79 nM (pChEMBL 8.550000190734863)
Descriptors: MW 346.52, ALogP 3.78, HBA 3, HBD 2, PSA 64.35, QED 0.57
Compound (SMILES): CCOc1ccc(C2(C[C@H](C)CCNCCCC(N)=O)CCC2)cc1
InChIKey: ZEFQZGJPKZZHJW-QGZVFWFLSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Radioligand Binding Assay: The monoamine transporters inhibitory activities of selected compounds cycloalkylmethylamine derivatives comprising Formula (I) are reported herein. The compounds were evaluated using well established radioligand binding assays protocols (Galli, A. et al., J. Exp. Biol. 1995, 198, 2197-2212; Giros, B. et al., Trends Pharmcol. Sci. 1993, 14, 43-49; Gu, H. et al., J. Biol. Chem. 1994, 269(10), 7124-7130; Shearman, L. P. et al, Am. J. Physiol., 1998, 275(6 Pt 1), C1621-1629; Wolf, W. A. et al., J. Biol. Chem. 1992, 267(29), 20820-20825). The human recombinant transporter proteins dopamine (DAT), norepinephrine (NET) and serotonin (SERT) were selected for the in vitro assays. The radioligand binding assays were carried out at 11 different test concentrations 0.1 nm to 1 μM.
Measurement: Ki = 328.9 nM (pChEMBL 6.480000019073486)
Descriptors: MW 346.52, ALogP 3.78, HBA 3, HBD 2, PSA 64.35, QED 0.57
Compound (SMILES): Cc1cc(C(=O)NC(Cc2ccccc2)C(O)CNC(C(=O)NCC(C)C)C(C)O)cc(C(=O)N(C)C(C)c2ccccc2)c1
InChIKey: ZKMCMCMWGYTFGC-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: Previously, one of the following compounds discussed below have been studied in memapsin 2 inhibition (Ghosh et al., 2008), which the others are previously unpublished. Given the closely related substrate specificity for memapsin 1 and memapsin 2, the inventors chose to screen these previously identified memapsin 2 inhibitors for lead compounds as memapsin 1 inhibitors. Recombinant memapsin 1 ectodomain was prepared as described by Turner et al. (2002) and assayed using a commercially purchased fluorescent substrate.
Measurement: Ki = 1657 nM (pChEMBL 5.78000020980835)
Descriptors: MW 616.8, ALogP 3.64, HBA 6, HBD 5, PSA 131, QED 0.18
Compound (SMILES): Cc1cc2c(C(=O)Cc3ccccc3)c(O)c(O)cc2c(O)c1-c1c(C)cc2c(C(=O)Cc3ccccc3)c(O)c(O)cc2c1O
InChIKey: IDXSKODLTDOMPF-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of Flu-BakBH3 peptide binding to GST-tagged Bcl-xL (unknown origin) preincubated for 10 mins followed by substrate addition measured after 30 mins by fluorescence polarization assay
Measurement: Ki = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 614.65, ALogP 7.36, HBA 8, HBD 6, PSA 155.52, QED 0.08
Compound (SMILES): Cc1cc2c(C(=O)c3cccc4ccccc34)c(O)c(O)cc2c(O)c1-c1c(C)cc2c(C(=O)c3cccc4ccccc34)c(O)c(O)cc2c1O
InChIKey: GBLSESKAVMAIIN-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Isothermal Titration Calorimetry Assays: Titrations were performed using a VP-ITC or ITC200 calorimeter from Microcal (Northampton, Mass.). BCL-XL was used at concentrations between 25 and 100 μM in 20 mM sodium phosphate buffer (pH 7.4) and 5-10% DMSO. Titrants were used at concentrations 10-15× of the protein in the same buffer. Titrations were carried out at 25° C. Data were analyzed using Microcal Origin software provided by the ITC manufacturer (Microcal, Northampton, Mass.).
Measurement: Kd = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 686.72, ALogP 9.28, HBA 8, HBD 6, PSA 155.52, QED 0.08
Compound (SMILES): Cc1ccc(CC(=O)c2c(O)c(O)cc3c(O)c(-c4c(C)cc5c(C(=O)Cc6ccc(C)cc6)c(O)c(O)cc5c4O)c(C)cc23)cc1
InChIKey: BRDPEGAOEASGCO-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Isothermal Titration Calorimetry Assays: Titrations were performed using a VP-ITC or ITC200 calorimeter from Microcal (Northampton, Mass.). BCL-XL was used at concentrations between 25 and 100 μM in 20 mM sodium phosphate buffer (pH 7.4) and 5-10% DMSO. Titrants were used at concentrations 10-15× of the protein in the same buffer. Titrations were carried out at 25° C. Data were analyzed using Microcal Origin software provided by the ITC manufacturer (Microcal, Northampton, Mass.).
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 642.7, ALogP 7.98, HBA 8, HBD 6, PSA 155.52, QED 0.08
Compound (SMILES): N#CC1CCCN1C(=O)CNCC(O)COc1ccccc1
InChIKey: IRTKELPEZOBDMX-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Inhibition Assay: Human recombinant adrenergic β1 receptors expressed in CHO-K1 cells are used in modified Tris-HCl buffer pH 7.4. A 25 aliquot is incubated with 0.03 nM [125I]Cyanopindolol for 120 minutes at 25° C. Non-specific binding is estimated in the presence of 100 μM S(−)-Propranolol. Receptors are filtered and washed, the filters are then counted to determine [125I]Cyanopindolol specifically bound. Compounds are screened at 10 μM.
Measurement: Ki = 9830 nM (pChEMBL 5.010000228881836)
Descriptors: MW 303.36, ALogP 0.53, HBA 5, HBD 2, PSA 85.59, QED 0.77
Compound (SMILES): CC(C)CC1C(=O)N(C(Cc2ccccc2)C(=O)O)C(=O)C1c1ccc(O)cc1
InChIKey: YVDGEXSSVKMMEG-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1a (isolate H) (HCV)
UniProt: P27958
Assay: Inhibition Assay: In addition, the dipeptidyl peptidase-IV (DPPIV) assay herein was applied to investigate the DPPIV inhibitory activity of the prepared compounds as described above. The method of the DPPIV assay was described in Lin et al., 1998. Inhibition of dipeptidyl peptidase IV by fluoroolefin-containing N-peptidyl-O-hydroxylamine peptidomimetics. Proc. Natl. Acad. Sci. USA Vol. 95, pp. 14020-14024.
Measurement: IC50 = 90000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 395.46, ALogP 3.2, HBA 4, HBD 2, PSA 94.91, QED 0.7
Compound (SMILES): CC(C)CC1C(=O)N(C(CO)C(=O)O)C(=O)C1c1ccc(O)cc1
InChIKey: ULAHURMFRLEUCJ-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1a (isolate H) (HCV)
UniProt: P27958
Assay: Inhibition Assay: In addition, the dipeptidyl peptidase-IV (DPPIV) assay herein was applied to investigate the DPPIV inhibitory activity of the prepared compounds as described above. The method of the DPPIV assay was described in Lin et al., 1998. Inhibition of dipeptidyl peptidase IV by fluoroolefin-containing N-peptidyl-O-hydroxylamine peptidomimetics. Proc. Natl. Acad. Sci. USA Vol. 95, pp. 14020-14024.
Measurement: IC50 = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 335.36, ALogP 0.95, HBA 5, HBD 3, PSA 115.14, QED 0.67
Compound (SMILES): CC(C)=CCOc1ccc(C2C(=O)N(O)C(=O)/C2=C\C(C)C)cc1
InChIKey: CIBYRBNESSOEJP-WJDWOHSUSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1a (isolate H) (HCV)
UniProt: P27958
Assay: Protease Assay: The HCV protease assay herein was applied to investigate the HCV-protease inhibitory activity of the prepared compounds as described above. The method of the HCV protease assay was described in D. T. Phuong, C. M. Ma, M. Hattori and J. S. J in: Inhibitory Effects of Antrodins A-E from Antrodia cinnamomea and Their Metabolites on Hepatitis C Virus Protease. Phytotherapy Research, 23, 582-584, 2009. Two micro liters of a compound solution (using DMSO as solvent) was placed in 384 well micro plate, then 8 ul of HCV NS3/4A protease (0.5 g/mL) was added to the well containing a sample and the plate was agitated. Finally, 10 uL of freshly prepared substrate (Ac-Asp-Glu-Dap(QXL 520)-Glu-Glu-Abu-COO-Ala-Ser-Cys(5-FAMsp)-NH2) (100 dilution of a DMSO stock solution) was added with sequential rotational shaking. The reaction mixture was incubated for 30 min at 37 C. The fluorimetric analyses were performed on an automated TECAN GENios plate reader with excitation wavelength at 485 nm.
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 329.4, ALogP 3.46, HBA 4, HBD 1, PSA 66.84, QED 0.39
Compound (SMILES): Cc1cnc(-c2ccnc(C(C)(C)O)n2)cc1-n1c(C)cc(OCc2ncc(F)cc2F)c(Cl)c1=O
InChIKey: FQPQMJULRZINPV-UHFFFAOYSA-N
Target: MAP kinase-activated protein kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IW41
Assay: IMAP Assay: The ability of compounds to inhibit activated phospho-p38alpha is evaluated using a p38alpha /MK2 and a p38alpha /PRAK cascade assay format. The kinase activity of p38alpha is determined by its ability to phosphorylate GST-MK2 or GST-PRAK. Activation of MK2 or PRAK by p38alpha is quantitated by measuring the phosphorylation of a fluorescently-labeled, MK2/PRAK specific peptide substrate, Hsp27 peptide (FITC-KKKALSRQLSVAA). The phosphorylation of the Hsp27 peptide is quantified using IMAP technology (Molecular Devices, Sunnyvale Calif.). Kinase reactions are carried out in a 384-well plate (Greiner, 781280) in 20 mM HEPES pH 7.5, 10 mM MgCl2, 0.01% Triton X-100, 0.01% BSA, 1 mM DTT, and 2% DMSO. The inhibitor concentration is varied between 0.02-30,000 nM, while the Hsp27 peptide substrate and MgATP are held constant at 1 uM and 10 uM, respectively. Activated p38alpha is added to a final concentration of 30 uM for reactions with nonphosphorylated 1 nM GST-MK2.
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 513.93, ALogP 4.44, HBA 8, HBD 1, PSA 103.02, QED 0.41
Compound (SMILES): CC#CCOc1ccc(C(=O)NC[C@@H](C(=O)NO)N2CCN(S(C)(=O)=O)CC2)cc1
InChIKey: GHBQSNPRMVUGFE-KRWDZBQOSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Enzyme Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAMS and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 438.51, ALogP -0.73, HBA 7, HBD 3, PSA 128.28, QED 0.28
Compound (SMILES): Cc1cc(COc2ccc(C(=O)NC[C@@H](C(=O)NO)N3CCN(S(C)(=O)=O)CC3)cc2)c2ccccc2n1
InChIKey: PNRXTCCMSJTZGK-DEOSSOPVSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13443
Assay: Enzyme Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAMS and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 541.63, ALogP 1.3, HBA 8, HBD 3, PSA 141.17, QED 0.27
Compound (SMILES): O=C(NCC(C(=O)NO)N1CCN(Cc2ccccc2)CC1)c1ccc(OCc2c(C(F)(F)F)nn3ccccc23)cc1
InChIKey: PWHWIWBGOFSUOR-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Enzyme Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAMS and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 596.61, ALogP 3.35, HBA 8, HBD 3, PSA 111.44, QED 0.19
Compound (SMILES): C#Cc1ccc(NC(=O)O[C@H]2C[C@@H](C)C=C3C=C[C@H](C)[C@H](CC[C@@H]4C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O4)[C@H]32)cc1
InChIKey: HWWVAOJWOSZHRO-FIBNWJQGSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Fluorescent Activity Assay: The HDAC activity was performed using the HDAC fluorescent activity assay kit (BIOMOL, Plymouth Meeting, Pa., USA) according to the manufacturer's instructions. Briefly, recombinant proteins of HDAC1 or HDAC6 were incubated with test compounds, and HDAC reaction was initiated by addition of Fluor-de-Lys substrate. Samples were incubated for 10 min at room temperature, followed by adding developer to stop the reaction. Fluorescence was measured by fluorometric reader with excitation at 360 nm and emission at 460 nm. The HDAC activity was expressed as arbitrary fluorescence units (AFU).
Measurement: IC50 = 127.4 nM (pChEMBL 6.889999866485596)
Descriptors: MW 577.84
Compound (SMILES): C#Cc1ccc(CNC(=O)O[C@H]2C[C@@H](C)C=C3C=C[C@H](C)[C@H](CC[C@@H]4C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O4)[C@H]32)cc1
InChIKey: YAHJAESFRLNRDH-RZSQEPJQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Fluorescent Activity Assay: The HDAC activity was performed using the HDAC fluorescent activity assay kit (BIOMOL, Plymouth Meeting, Pa., USA) according to the manufacturer's instructions. Briefly, recombinant proteins of HDAC1 or HDAC6 were incubated with test compounds, and HDAC reaction was initiated by addition of Fluor-de-Lys substrate. Samples were incubated for 10 min at room temperature, followed by adding developer to stop the reaction. Fluorescence was measured by fluorometric reader with excitation at 360 nm and emission at 460 nm. The HDAC activity was expressed as arbitrary fluorescence units (AFU).
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 591.87
Compound (SMILES): Cc1cc(C)nc(N[C@@H]2CCCN(C(=O)c3ccc(F)cc3-n3nccn3)[C@H]2C)n1
InChIKey: GWKDUSDVRZEFJY-MAUKXSAKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 409.47, ALogP 2.92, HBA 7, HBD 1, PSA 88.83, QED 0.71
Compound (SMILES): Cc1cc(C)nc(N[C@@H]2CCCN(C(=O)c3c(F)cccc3-c3ncccn3)[C@H]2C)n1
InChIKey: PGWAAWMSURLNEZ-QFBILLFUSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 420.49, ALogP 3.79, HBA 6, HBD 1, PSA 83.9, QED 0.69
Compound (SMILES): Cc1cc(C)nc(N[C@@H]2CCCN(C(=O)c3c(F)cccc3-n3nccn3)[C@H]2C)n1
InChIKey: HKZPAQNNMSEXPQ-DOTOQJQBSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 409.47, ALogP 2.92, HBA 7, HBD 1, PSA 88.83, QED 0.71
Compound (SMILES): Cc1cc(C)nc(N[C@@H]2CCCN(C(=O)c3ccccc3-n3nccn3)[C@H]2C)n1
InChIKey: MGKAPAIPNKGNLB-FUHWJXTLSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 391.48, ALogP 2.78, HBA 7, HBD 1, PSA 88.83, QED 0.74