lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(-c2cn3c(n2)-c2ccc(N4CCCC4C4CCCN(C)C4)cc2OCC3)n(C(C)C)n1
InChIKey: XUSKNOLOZFGDSE-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 = 5.68 nM (pChEMBL 8.25)
Descriptors: MW 475.64, ALogP 4.4, HBA 8, HBD 0, PSA 64.24, QED 0.56
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 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
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 = 450 nM (pChEMBL 6.349999904632568)
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: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
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 = 4300 nM (pChEMBL 5.369999885559082)
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 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 = 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 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 = 5.7 nM (pChEMBL 8.239999771118164)
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 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 = 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 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 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 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 = 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 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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 374.57, ALogP 4.43, HBA 3, HBD 2, PSA 50.36, QED 0.53
Compound (SMILES): C[C@@H](CCNCCCC(N)=O)CC1(c2ccc(Cl)c(Cl)c2)CCC1
InChIKey: OZLLUGNMXJLQIE-AWEZNQCLSA-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 = 2.3 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 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 = 299.7 nM (pChEMBL 6.519999980926514)
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 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 = 5.49 nM (pChEMBL 8.260000228881836)
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 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 = 2.79 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 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 = 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): 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: Fluorescence Polarization Assays: A Bak BH3 peptide (F-BakBH3) (GQVGRQLAIIGDDINR) was labeled at the N-terminus with fluorescein isothiocyanate (FITC) (Molecular Probes) and purified by HPLC. For competitive binding assays, 100 nM GST-BCL-XL DTM protein was preincubated with the tested compound at varying concentrations in 47.5 uL PBS (pH=7.4) in 96-well black plates at room temperature for 10 min, then 2.5 uL of 100 nM FITC-labeled Bak BH3 peptide was added to produce a final volume of 50 uL. The wild-type and mutant Bak BH3 peptides were included in each assay plate as positive and negative controls, respectively.After 30 min incubation at room temperature, the polarization values in millipolarization units were measured at excitation/emission wavelengths of 480/535 nm with a multilabel plate reader (PerkinElmer). IC50 was determined by fitting the experimental data to a sigmoidal dose-response nonlinear regression model (SigmaPlot 10.0.1, Systat Software, Inc., San Jose, Calif., USA).
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 614.65, ALogP 7.36, HBA 8, HBD 6, PSA 155.52, QED 0.08
Compound (SMILES): N#CC1CCCN1C(=O)CNCC(O)COc1ccccc1
InChIKey: IRTKELPEZOBDMX-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Inhibition Assay: Human recombinant adrenergic β2 receptors expressed in CHO cells are used in modified Tris-HCl buffer pH 7.4. A 50 aliquot is incubated with 0.2 nM [3H]CGP-12177 for 60 minutes at 25° C. Non-specific binding is estimated in the presence of 10 μM ICI-118551. Receptors are filtered and washed, the filters are then counted to determine [3H]CGP-12177 specifically bound. Compounds are screened at 10 μM.
Measurement: Ki = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 303.36, ALogP 0.53, HBA 5, HBD 2, PSA 85.59, QED 0.77
Compound (SMILES): CC#CCOc1ccc(C(=O)NC[C@@H](C(=O)NO)N2CCN(S(C)(=O)=O)CC2)cc1
InChIKey: GHBQSNPRMVUGFE-KRWDZBQOSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
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: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
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 = 6827 nM (pChEMBL 5.170000076293945)
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: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
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 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: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductase assay kit from Sigma-Aldrich with the human recombinant protein or 100 μg total cell lysates from A549 cells. Lovastatin was used as a positive control, and SAHA as a negative control. HMGR activity under defined assay conditions, containing NADPH and HMG-CoA substrate in a final volume of 0.2 mL of 100 mM potassium phosphatate buffer (120 mM KCI, 1 mM EDTA, 5 mM DTT, pH 7.4), were initiated in the presence or absence (control) of test compounds dissolved in dimethylsulfoxide (DMSO). The rates of NADPH consumption were monitored every 20 seconds, for up to 10 minutes, by spectrophotometer at 37° C. and 340 nm.
Measurement: IC50 = 36.5 nM (pChEMBL 7.440000057220459)
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: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductase assay kit from Sigma-Aldrich with the human recombinant protein or 100 μg total cell lysates from A549 cells. Lovastatin was used as a positive control, and SAHA as a negative control. HMGR activity under defined assay conditions, containing NADPH and HMG-CoA substrate in a final volume of 0.2 mL of 100 mM potassium phosphatate buffer (120 mM KCI, 1 mM EDTA, 5 mM DTT, pH 7.4), were initiated in the presence or absence (control) of test compounds dissolved in dimethylsulfoxide (DMSO). The rates of NADPH consumption were monitored every 20 seconds, for up to 10 minutes, by spectrophotometer at 37° C. and 340 nm.
Measurement: IC50 = 53.8 nM (pChEMBL 7.269999980926514)
Descriptors: MW 591.87
Compound (SMILES): Cc1ccc(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)c(-n2nccn2)c1
InChIKey: ZRBIBMLFZDCZSU-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 = 681 nM (pChEMBL 6.170000076293945)
Descriptors: MW 444.46, ALogP 4.09, HBA 6, HBD 1, PSA 75.94, QED 0.66
Compound (SMILES): CCOc1ccc(C)nc1C(=O)N1CCC[C@@H](Nc2ccc(C(F)(F)F)cn2)[C@@H]1C
InChIKey: WBNDJIUHFUOZRK-GOEBONIOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Studies: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat #SH30022), 10% FBS, 1×Pen/Strep, 1× sodium pyruvate, 10 mM HEPES, 600 μg/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1×Pen/Strep, 600 μg/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat #SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° 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 prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-(1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Moraveck Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-(1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 422.45, ALogP 4.31, HBA 5, HBD 1, PSA 67.35, QED 0.78
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)n1
InChIKey: DLKBIPTYSSGNMW-GOEBONIOSA-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 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 445.45, ALogP 3.49, HBA 7, HBD 1, PSA 88.83, QED 0.66
Compound (SMILES): Cc1ccc(-c2ncco2)c(C(=O)N2CCC[C@@H](Nc3ccc(C(F)(F)F)cn3)[C@@H]2C)n1
InChIKey: PRBOUMKUMAGYMX-WMLDXEAASA-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 = 422 nM (pChEMBL 6.380000114440918)
Descriptors: MW 445.45, ALogP 4.56, HBA 6, HBD 1, PSA 84.15, QED 0.63
Compound (SMILES): C[C@H]1[C@H](Nc2ccc(Cl)cn2)CCCN1C(=O)c1ccccc1-n1nccn1
InChIKey: MJGKUUKCLJOFTN-WMLDXEAASA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor(Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, IX Pen/Strep, IX sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #1 1039), 10%FBS, IX Pen/Strep, 600 ug/mL G418 media, respectively 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 4 C), the supernatant was aspirated and the pellets frozen and stored at -80C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #1 1836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL.
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 396.88, ALogP 3.42, HBA 6, HBD 1, PSA 75.94, QED 0.73
Compound (SMILES): C[C@H]1[C@H](Nc2cnc(C(F)(F)F)cn2)CCCN1C(=O)c1ccccc1-n1nccn1
InChIKey: UTXHBVDKNQOXIE-DZGCQCFKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor(Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, IX Pen/Strep, IX sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #1 1039), 10%FBS, IX Pen/Strep, 600 ug/mL G418 media, respectively 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 4 C), the supernatant was aspirated and the pellets frozen and stored at -80C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #1 1836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL.
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 431.42, ALogP 3.18, HBA 7, HBD 1, PSA 88.83, QED 0.68
Compound (SMILES): CCCCSc1ncnc2c1ncn2[C@@H]1O[C@H]([C@H](CSCC[C@H](N)C(=O)O)OP(=O)(O)OP(=O)(O)NP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: JSGYFHBIHPBINR-REWAFKANSA-N
Target: S-adenosylmethionine synthase isoform type-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P13444
Assay: Inhibition constants against Met (L-methionine)P substrate site of M-T (Novikoff Ascitic Hepatoma form) variant of rat Methionine adenosyltransferase
Measurement: Ki = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 726.56, ALogP 0.16, HBA 16, HBD 9, PSA 319.23, QED 0.04
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H]([C@H](CSCCC(N)C(=O)O)OP(=O)(O)OP(=O)(O)NP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: FBOLNTODBBAPDR-CHCQOLDJSA-N
Target: S-adenosylmethionine synthase isoform type-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P13444
Assay: Inhibition constants against Met (L-methionine)P substrate site of M-T (Novikoff Ascitic Hepatoma form) variant of rat Methionine adenosyltransferase
Measurement: Ki = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 653.4, ALogP -2.15, HBA 16, HBD 10, PSA 345.25, QED 0.08
Compound (SMILES): CC(C)(c1ncc(-c2cccnc2)o1)N1CCN(C[C@@H](O)C[C@@H](Cc2ccccc2)C(=O)N[C@H]2c3ccccc3OC[C@H]2O)[C@H](C(=O)NCC(F)(F)F)C1
InChIKey: TWZWSIXDZUIEIJ-BEILRLPOSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver microsome Cytochrome P450 2C9
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 750.82, ALogP 3.86, HBA 10, HBD 4, PSA 153.29, QED 0.16
Compound (SMILES): COc1cncc(-c2cnc(C(C)(C)N3CCN(C[C@@H](O)C[C@@H](Cc4ccccc4)C(=O)N[C@H]4c5ccccc5OC[C@H]4O)[C@H](C(=O)NCC(F)(F)F)C3)o2)c1
InChIKey: CWAPFPHVCGEYRK-YKTJUOTHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver microsome Cytochrome P450 2C9
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 780.85, ALogP 3.87, HBA 11, HBD 4, PSA 162.52, QED 0.15
Compound (SMILES): O=C(N[C@H]1c2ccccc2OC[C@H]1O)[C@H](Cc1ccccc1)C[C@H](O)CN1CCN(Cc2ccc(-c3ccccn3)o2)C[C@H]1C(=O)NCC(F)(F)F
InChIKey: VJEYRJGOROCIKW-NKDCNHMZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: In vitro inhibition of human liver microsome Cytochrome P450 3A4
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 721.78, ALogP 3.73, HBA 9, HBD 4, PSA 140.4, QED 0.16
Compound (SMILES): CC(C)(c1ccc(-c2ccncc2)o1)N1CCN(C[C@@H](O)C[C@@H](Cc2ccccc2)C(=O)N[C@H]2c3ccccc3OC[C@H]2O)[C@H](C(=O)NCC(F)(F)F)C1
InChIKey: DYYJWDSYFDXNOW-FLOLVYIHSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibitory activity against HIV-1 Protease from PI-resistant HIV-1 (strain Q-18C)
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 749.83, ALogP 4.46, HBA 9, HBD 4, PSA 140.4, QED 0.16
Compound (SMILES): CC(C)(c1ncc(-c2ccccn2)o1)N1CCN(C[C@@H](O)C[C@@H](Cc2ccccc2)C(=O)N[C@H]2c3ccccc3OC[C@H]2O)[C@H](C(=O)NCC(F)(F)F)C1
InChIKey: RTAOSKPTWQTCBX-GIWSTSDLSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver microsome Cytochrome P450 2C9
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 750.82, ALogP 3.86, HBA 10, HBD 4, PSA 153.29, QED 0.16
Compound (SMILES): CC(C)(c1ncc(-c2cnccc2Cl)o1)N1CCN(C[C@@H](O)C[C@@H](Cc2ccccc2)C(=O)N[C@H]2c3ccccc3OC[C@H]2O)[C@H](C(=O)NCC(F)(F)F)C1
InChIKey: ZHHNHYJWRCZSIY-JJCSDTKMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver microsome Cytochrome P450 2C9
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 785.26, ALogP 4.51, HBA 10, HBD 4, PSA 153.29, QED 0.15
Compound (SMILES): O=C(N[C@H]1c2ccccc2OC[C@H]1O)[C@H](Cc1ccccc1)C[C@H](O)CN1CCN(Cc2ccc(-c3cccnc3)o2)C[C@H]1C(=O)NCC(F)(F)F
InChIKey: MAMJAUDDHCPYJQ-WZXFIOQESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: In vitro inhibition of human liver microsome Cytochrome P450 3A4
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 721.78, ALogP 3.73, HBA 9, HBD 4, PSA 140.4, QED 0.16
Compound (SMILES): C#CC(OC1=CC(=O)C(Nc2ncnc3cc(OCCCN4CCCC4)c(OC)cc23)=CC1=O)c1ccccc1
InChIKey: JQSPJEYNFDJKEM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of poly(Glu4-Tyr)peptide phosphorylation by recombinant VEGFR2 at 1 mm ATP
Measurement: IC50 = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 538.6, ALogP 4.23, HBA 9, HBD 1, PSA 102.88, QED 0.22
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(OCCOc4ccccc4)=CC3=O)c2cc1OC
InChIKey: GUIGOOUYNPWPAN-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 491.5, ALogP 3.09, HBA 10, HBD 1, PSA 118.1, QED 0.3
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(N(C)c4ccccc4)=CC3=O)c2cc1OC
InChIKey: NFCSIRISBGUOEG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 460.49, ALogP 3.13, HBA 9, HBD 1, PSA 102.88, QED 0.38
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(OC)=CC3=O)c2cc1OC
InChIKey: NNSKLWXTYRGLMC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of poly(Glu4-Tyr)peptide phosphorylation by recombinant VEGFR2 at 1 mm ATP
Measurement: IC50 = 436.3 nM (pChEMBL 6.360000133514404)
Descriptors: MW 385.38, ALogP 1.64, HBA 9, HBD 1, PSA 108.87, QED 0.54
Compound (SMILES): COc1cc2c(NC3=CC(=O)C(OC(CF)CF)=CC3=O)ncnc2cc1OCC1CCN(C)CC1
InChIKey: FTDHOACXVYZSHC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of poly(Glu4-Tyr)peptide phosphorylation by recombinant VEGFR2 at 1 mm ATP
Measurement: IC50 = 11.2 nM (pChEMBL 7.949999809265137)
Descriptors: MW 502.52, ALogP 3.01, HBA 9, HBD 1, PSA 102.88, QED 0.49
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(SC)=CC3=O)c2cc1OC
InChIKey: DANRECYHPDNQGT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of poly(Glu4-Tyr)peptide phosphorylation by recombinant VEGFR2 at 1 mm ATP
Measurement: IC50 = 43.3 nM (pChEMBL 7.360000133514404)
Descriptors: MW 401.44, ALogP 2.36, HBA 9, HBD 1, PSA 99.64, QED 0.53
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(OCC(F)F)=CC3=O)c2cc1OC
InChIKey: GPGNMTNUZNOGIB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 435.38, ALogP 2.28, HBA 9, HBD 1, PSA 108.87, QED 0.44
Compound (SMILES): COCCOc1cc2ncnc(NC3=CC(=O)C(N4CC(C)OC4=O)=CC3=O)c2cc1OC
InChIKey: WJHGKFUOCDSBSI-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of poly(Glu4-Tyr)peptide phosphorylation by recombinant VEGFR2 at 1 mm ATP
Measurement: IC50 = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 454.44, ALogP 1.84, HBA 10, HBD 1, PSA 129.18, QED 0.47
Compound (SMILES): COc1cc2c(NC3=CC(=O)C(OCC#Cc4ccccc4)=CC3=O)ncnc2cc1OCCCN1CCCC1
InChIKey: UHVIRIZFQYNLSJ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of poly(Glu4-Tyr)peptide phosphorylation by recombinant VEGFR2 at 1 mm ATP
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 538.6, ALogP 3.9, HBA 9, HBD 1, PSA 102.88, QED 0.23
Compound (SMILES): COc1cc2c(NC3=CC(=O)C(OCc4ccccc4)=CC3=O)ncnc2cc1OCC1CCN(C)CC1
InChIKey: UDIFASWVFVVHEQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibitory activity against VEGF stimulated autophosphorylation of VEGFR2 expressed in KDR15 cells
Measurement: IC50 = 536 nM (pChEMBL 6.269999980926514)
Descriptors: MW 514.58, ALogP 3.91, HBA 9, HBD 1, PSA 102.88, QED 0.43
Compound (SMILES): CCC(=O)N1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)CC1
InChIKey: UFLFYKRXLZELNB-SANMLTNESA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin
Measurement: Ki = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 601.69, ALogP 1.72, HBA 7, HBD 3, PSA 170.8, QED 0.2
Compound (SMILES): N=C(N)c1cccc(C[C@H](NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)C(=O)N2CCC(C(=O)NCCN)CC2)c1
InChIKey: ONGKRKOCNOAMPQ-MHZLTWQESA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of uPA
Measurement: Ki = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 630.73, ALogP 0.95, HBA 8, HBD 5, PSA 205.61, QED 0.13
Compound (SMILES): N=C(N)NCCNC(=O)C1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)CC1
InChIKey: ASERQAPACCCWLA-MHZLTWQESA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of plasmin
Measurement: Ki = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 672.77, ALogP 0.47, HBA 8, HBD 7, PSA 241.49, QED 0.07
Compound (SMILES): N=C(N)NCCC(=O)N1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2ccc3c(c2)C(=O)c2ccccc2C3=O)CC1
InChIKey: BFGMZJACHSZEKY-SANMLTNESA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of uPA
Measurement: Ki = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 658.74, ALogP 0.18, HBA 8, HBD 6, PSA 232.7, QED 0.1
Compound (SMILES): O=C(O)c1cc(Cc2cc(Cc3ccccc3)c(O)c(C(=O)O)c2)cc(Cc2ccccc2)c1O
InChIKey: BIFGIRDZFXPUKP-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of SHP-1 catalytic domain
Measurement: Ki = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 468.51, ALogP 5.27, HBA 4, HBD 4, PSA 115.06, QED 0.28
Compound (SMILES): C[C@H]1CN(c2cccc3cc(F)ccc23)CCN1CC[C@@H]1OCc2cc(C(N)=O)ccc21
InChIKey: IEEIKXULGHBDHP-GKVSMKOHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]raclopride from dopamine D2 receptor in rat caudate membranes
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 433.53, ALogP 4.25, HBA 4, HBD 1, PSA 58.8, QED 0.65
Compound (SMILES): C[C@H]1CN(c2cccc3cc(F)ccc23)CCN1CC[C@H]1OCc2cc(C(N)=O)ccc21
InChIKey: IEEIKXULGHBDHP-SSOJOUAXSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]raclopride from dopamine D2 receptor in rat caudate membranes
Measurement: Ki = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 433.53, ALogP 4.25, HBA 4, HBD 1, PSA 58.8, QED 0.65
Compound (SMILES): C[C@H]1CN(c2cccc3cc(C#N)ccc23)CCN1CC[C@H]1OCc2cc(C(N)=O)ccc21
InChIKey: UXFUUSSXWKKNGT-HFJWLAOPSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]raclopride from dopamine D2 receptor in rat caudate membranes
Measurement: Ki = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 440.55, ALogP 3.98, HBA 5, HBD 1, PSA 82.59, QED 0.65
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccccc1F)O2)C(C)=CC(C)(C)N3
InChIKey: MPVGXDFFAWVSJS-XKZIYDEJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 429.49, ALogP 6.7, HBA 4, HBD 2, PSA 50.72, QED 0.48
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccccc1Cl)O2)C(C)=CC(C)(C)N3
InChIKey: HMMVFRHRYDHPGJ-XKZIYDEJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 445.95, ALogP 7.22, HBA 4, HBD 2, PSA 50.72, QED 0.44
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccccc1C)O2)C(C)=CC(C)(C)N3
InChIKey: ZQEWPYDDJWJFGN-UCQKPKSFSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 425.53, ALogP 6.87, HBA 4, HBD 2, PSA 50.72, QED 0.47
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccccc1-c1ccccc1)O2)C(C)=CC(C)(C)N3
InChIKey: CHFIJDHNUPEFNJ-VEILYXNESA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 487.6, ALogP 8.23, HBA 4, HBD 2, PSA 50.72, QED 0.31
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccc(F)cc1C(=O)N(C)C)O2)C(C)=CC(C)(C)N3
InChIKey: DQCMNTREKFBHIX-CFRMEGHHSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 500.57, ALogP 6.41, HBA 5, HBD 2, PSA 71.03, QED 0.44
Compound (SMILES): CCN(CC)Cc1cc(F)ccc1/C=C1\Oc2ccc(O)c(OC)c2-c2ccc3c(c21)C(C)=CC(C)(C)N3
InChIKey: FMEMNWKGLCXAJV-YUMHPJSZSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 514.64, ALogP 7.55, HBA 5, HBD 2, PSA 53.96, QED 0.36
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccc(F)cc1C(=O)N1CCCCC1)O2)C(C)=CC(C)(C)N3
InChIKey: LKFJGNOTTYBGRI-YUMHPJSZSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 540.64, ALogP 7.33, HBA 5, HBD 2, PSA 71.03, QED 0.36
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccc(F)cc1S(=O)(=O)N1CCCCC1)O2)C(C)=CC(C)(C)N3
InChIKey: BXLFJXWEWKULTF-QQXSKIMKSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 576.69, ALogP 6.88, HBA 6, HBD 2, PSA 88.1, QED 0.35
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccc(F)cc1CO)O2)C(C)=CC(C)(C)N3
InChIKey: PNVTUJVNNJCYGM-FMCGGJTJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 459.52, ALogP 6.2, HBA 5, HBD 3, PSA 70.95, QED 0.44
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1ccc(F)cc1/C=N/O)O2)C(C)=CC(C)(C)N3
InChIKey: ZRGBFWZKPKHTBN-VYADKDSNSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Activity at GR assessed as repression of TNFalpha and IL 1-beta induced E-selectin response
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 472.52, ALogP 6.51, HBA 6, HBD 3, PSA 83.31, QED 0.23
Compound (SMILES): COCOCc1cc(F)ccc1/C=C1\Oc2ccc(O)c(OC)c2-c2ccc3c(c21)C(C)=CC(C)(C)N3
InChIKey: OTWADYHEAKBKQC-MXAYSNPKSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at GR assessed as inhibition of dexamethasone-induced GRE activation
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 503.57, ALogP 6.83, HBA 6, HBD 2, PSA 69.18, QED 0.28
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(C)c1)O2)C(C)=CC(C)(C)N3
InChIKey: DPPNIDONMQTQMK-UCQKPKSFSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Displacement of radiolabeled Dexamethasone from glucocorticoid receptor
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 425.53, ALogP 6.87, HBA 4, HBD 2, PSA 50.72, QED 0.47
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(C(F)(F)F)c1)O2)C(C)=CC(C)(C)N3
InChIKey: DWKQZGCDDFUDBR-XKZIYDEJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Displacement of radiolabeled Dexamethasone from glucocorticoid receptor
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 479.5, ALogP 7.58, HBA 4, HBD 2, PSA 50.72, QED 0.4
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(-c4ccccc4)c1)O2)C(C)=CC(C)(C)N3
InChIKey: DPNNWDJFUPUIPT-VEILYXNESA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Displacement of radiolabeled Dexamethasone from glucocorticoid receptor
Measurement: Ki = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 487.6, ALogP 8.23, HBA 4, HBD 2, PSA 50.72, QED 0.31
Compound (SMILES): COc1c(O)ccc2c1-c1ccc3c(c1/C(=C/c1cccc(O)c1)O2)C(C)=CC(C)(C)N3
InChIKey: LEOCLJZACQHETJ-XKZIYDEJSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Displacement of radiolabeled Dexamethasone from glucocorticoid receptor
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 427.5, ALogP 6.27, HBA 5, HBD 3, PSA 70.95, QED 0.45