lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)SC(C)(C)c1ccc(NC(=O)c2ncc(C#N)[nH]2)c(C2=CCC(C)(C)CC2)c1
InChIKey: XBRPHSVIQICANS-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Fluorescence Polarization Competition Assay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 μL of compound (in 4% DMSO) were mixed with 2 μL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 μL of 1540 μM peptide in assay buffer. The kinase reaction was initiated by adding 1 μL of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 μM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R.
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 436.58, ALogP 5.64, HBA 5, HBD 2, PSA 98.64, QED 0.63
Compound (SMILES): Cc1cccc(NC(C)(C)c2ccc(NC(=O)c3ncc(C#N)[nH]3)c(C3=CCC(C)(C)CC3)c2)n1
InChIKey: NEPVAQXTHWVVHM-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Fluorescence Polarization Competition Immunoassay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 uL of compound (in 4% DMSO) were mixed with 2 uL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 uL of 1540 uM peptide in assay buffer. The kinase reaction was initiated by adding 1 Î¼L of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 uM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R. Positive and negative control wells were included on each plate, where 4% DMSO in assay buffer was substituted for the compound; in addition, positive control wells received 1.2 uL of 50 mM EDTA (ethylenediaminetetraacetic acid) before the start of the reaction.
Measurement: IC50 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 468.61, ALogP 6.18, HBA 5, HBD 3, PSA 106.49, QED 0.4
Compound (SMILES): CCOC(=O)CN1CCN(C(C)(C)c2ccc(NC(=O)c3ncc(C#N)[nH]3)c(C3=CCC(C)(C)CC3)c2)CC1
InChIKey: DLFJAVXYNBRXOG-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Fluorescence Polarization Competition Immunoassay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 uL of compound (in 4% DMSO) were mixed with 2 uL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 uL of 1540 uM peptide in assay buffer. The kinase reaction was initiated by adding 1 Î¼L of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 uM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R. Positive and negative control wells were included on each plate, where 4% DMSO in assay buffer was substituted for the compound; in addition, positive control wells received 1.2 uL of 50 mM EDTA (ethylenediaminetetraacetic acid) before the start of the reaction.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 532.69, ALogP 4.54, HBA 7, HBD 2, PSA 114.35, QED 0.48
Compound (SMILES): CSCCNCC(C)(C)c1ccc(NC(=O)c2nc(C#N)c[nH]2)c(C2=CCC(C)(C)CC2)c1
InChIKey: SCHJBAIWWCHNIF-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Fluorescence Polarization Competition Assay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 μL of compound (in 4% DMSO) were mixed with 2 μL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 μL of 1540 μM peptide in assay buffer. The kinase reaction was initiated by adding 1 μL of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 μM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 465.67, ALogP 5.36, HBA 5, HBD 3, PSA 93.6, QED 0.43
Compound (SMILES): CC1(C)CC=C(c2cc(C(C)(C)CN3C[C@@H]4OC(C)(C)O[C@@H]4C3)ccc2NC(=O)c2ncc(C#N)[nH]2)CC1
InChIKey: SWFQNHQEKMAWNJ-PLQXJYEYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Inhibition of c-fms in mouse bone marrow macrophages assessed as reduction in recombinant mouse CSF-1-driven cell proliferation by measuring bromodeoxyuridine incorporation incubated for 30 hrs by ELISA
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 517.67, ALogP 5.24, HBA 6, HBD 2, PSA 103.27, QED 0.54
Compound (SMILES): CC1(C)CC=C(c2cc(C(C)(C)CN3CCSCC3)ccc2NC(=O)c2nc(C#N)c[nH]2)CC1
InChIKey: TVSXNYPPUKMGJN-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Fluorescence Polarization Competition Immunoassay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 uL of compound (in 4% DMSO) were mixed with 2 uL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 uL of 1540 uM peptide in assay buffer. The kinase reaction was initiated by adding 1 Î¼L of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 uM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R. Positive and negative control wells were included on each plate, where 4% DMSO in assay buffer was substituted for the compound; in addition, positive control wells received 1.2 uL of 50 mM EDTA (ethylenediaminetetraacetic acid) before the start of the reaction.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 477.68, ALogP 5.45, HBA 5, HBD 2, PSA 84.81, QED 0.58
Compound (SMILES): CC(c1ccc(NC(=O)c2ncc(C#N)[nH]2)c(C2=CCC(C)(C)CC2)c1)N1C[C@@H](C)N[C@@H](C)C1
InChIKey: QRVDKFYXIGYWDP-DFNIBXOVSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Fluorescence Polarization Competition Assay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 μL of compound (in 4% DMSO) were mixed with 2 μL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 μL of 1540 μM peptide in assay buffer. The kinase reaction was initiated by adding 1 μL of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 μM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 460.63, ALogP 4.87, HBA 5, HBD 3, PSA 96.84, QED 0.59
Compound (SMILES): CC1(C)CC=C(c2cc(C(C)(C)N3CCCCC3)ccc2NC(=O)c2ncc(C#N)[nH]2)CC1
InChIKey: MGWBBOCKTHEAME-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Inhibition of c-fms in mouse bone marrow macrophages assessed as reduction in recombinant mouse CSF-1-driven cell proliferation by measuring bromodeoxyuridine incorporation incubated for 30 hrs by ELISA
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 445.61, ALogP 5.85, HBA 4, HBD 2, PSA 84.81, QED 0.6
Compound (SMILES): CC1(C)CC=C(c2cc(CN3CCNCC3)ccc2NC(=O)c2nc(C#N)c[nH]2)CC1
InChIKey: FCEGNRXMBLQREV-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Fluorescence Polarization Competition Immunoassay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 uL of compound (in 4% DMSO) were mixed with 2 uL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 uL of 1540 uM peptide in assay buffer. The kinase reaction was initiated by adding 1 Î¼L of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 uM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R. Positive and negative control wells were included on each plate, where 4% DMSO in assay buffer was substituted for the compound; in addition, positive control wells received 1.2 uL of 50 mM EDTA (ethylenediaminetetraacetic acid) before the start of the reaction.
Measurement: IC50 = 0.82 nM (pChEMBL 9.09000015258789)
Descriptors: MW 418.55, ALogP 3.53, HBA 5, HBD 3, PSA 96.84, QED 0.69
Compound (SMILES): C=C(C)c1ccc(NC(=O)c2ncc(C#N)[nH]2)c(C2=CCCCC2)c1
InChIKey: CJORAGJJZCSQMS-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Fluorescence Polarization Competition Immunoassay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 uL of compound (in 4% DMSO) were mixed with 2 uL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 uL of 1540 uM peptide in assay buffer. The kinase reaction was initiated by adding 1 Î¼L of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 uM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R. Positive and negative control wells were included on each plate, where 4% DMSO in assay buffer was substituted for the compound; in addition, positive control wells received 1.2 uL of 50 mM EDTA (ethylenediaminetetraacetic acid) before the start of the reaction.
Measurement: IC50 = 32.9 nM (pChEMBL 7.480000019073486)
Descriptors: MW 332.41, ALogP 4.52, HBA 3, HBD 2, PSA 81.57, QED 0.86
Compound (SMILES): NC(=O)c1c[nH]c(C(=O)Nc2ccc(CCC(=O)O)cc2C2=CCCCC2)n1
InChIKey: LUXRWROAGMQUNW-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Fluorescence Polarization Competition Immunoassay: A fluorescence polarization competition immunoassay was used to measure compound inhibition of CSF-1R phosphorylation of tyrosine on a synthetic CSF-1R555-568 peptide (SYEGNSYTFIDPTQ). The assay was performed in black 96-well microplates (Cat #42-000-0117, Molecular Devices, Sunnyvale, Calif.). To each well, 5 uL of compound (in 4% DMSO) were mixed with 2 uL of 3.5 nM CSF-1R, 25 mM MgCl2 in assay buffer (100 mM HEPES (hydroxyethylpiperazineethylsodiumsulfonate), pH 7.5, 1 mM DTT (dithiothreitol), 0.01% Tween-20), and 2 uL of 1540 uM peptide in assay buffer. The kinase reaction was initiated by adding 1 Î¼L of 10 mM ATP in assay buffer. The final concentrations in the 10 uL reaction mixture were 100 mM HEPES, pH 7.5, 1 mM DTT, 0.01% Tween-20, 2% DMSO, 308 uM SYEGNSYTFIDPTQ, 1 mM ATP, 5 mM MgCl2, and 0.7 nM CSF-1R. Positive and negative control wells were included on each plate, where 4% DMSO in assay buffer was substituted for the compound; in addition, positive control wells received 1.2 uL of 50 mM EDTA (ethylenediaminetetraacetic acid) before the start of the reaction.
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 382.42, ALogP 2.74, HBA 4, HBD 4, PSA 138.17, QED 0.58
Compound (SMILES): Cn1c(Nc2c(Cl)ccc(CNC(=O)C(C)(C)C)c2Cl)nc2cc(C(=O)NC3CCC(F)(F)CC3)c(N3CCC(C(F)(F)F)CC3)cc21
InChIKey: YNOQRNFBCBJGDF-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Enzyme Assay: The aim of this assay is to determine the affinity of a test compound for the mPGES-1 enzyme. 47 μl of recombinant human mPGES-1 (0.5 μg protein/well) containing microsomal suspension in a buffer containing GSH, (2.5 mmol/L L-Glutathione reduced, dissolved in 0.1 mol/L Phosphat Buffer pH 7.4) is dispensed in a 384-well plate and thereafter 1 μl of the test compound(s) is/are added and incubated for 25 minutes at room temperature. The enzyme reaction is started by the addition of 2 ul PGH2 (final conc 2 μM) disolved in water-free Diglyme. After 60 seconds the reaction is terminated by addition of a stop solution containing FeCl2 (10 μL 0.074 mol/l FeCl2). The samples are diluted between 1:25 in PBS (Phosphate Buffered Saline). 10 μl of the diluted samples are transferred to 384-well low volume plate.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 717.61, ALogP 8.37, HBA 6, HBD 3, PSA 91.29, QED 0.21
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3csc(N4CCN(C)CC4)n3)cc2)[C@@H]2C(=O)CO[C@H]12
InChIKey: FIJFMUKDMVGIOK-ZRYIBQHNSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Enzyme Assay: The assay uses baculovirus-expressed human cathepsin S and the boc-Val-Leu-Lys-AMC fluorescent substrate available from Bachem in a 384 well plate format, in which 7 test compounds can be tested in parallel with a positive control comprising a known cathepsin S inhibitor comparator. The first test compound prepared in DMSO is added to column 1 of the top row, typically at a volume to provide between 10 and 30 times the initially determined rough K. The rough Ki is calculated from a preliminary run in which 10 μl/well of 1 mM boc-VLK-AMC (1/10 dilution of 10 mM stock in DMSO diluted into assay buffer) is dispensed to rows B to H and 20 μl/well to row A of a 96 well Microfluor plate. 2 μl of each 10 mM test compound is added to a separate well on row A, columns 1-10. Add 90 μl assay buffer containing 1 mM DTT and 2 nM cathepsin S to each well of rows B-H and 180 μl to row A.
Measurement: Ki = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 549.7, ALogP 2.13, HBA 8, HBD 1, PSA 95.08, QED 0.53
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3nc(N4CCN(C)CC4)sc3F)cc2)[C@@H]2C(=O)CO[C@H]12
InChIKey: HUMYXJUMFCJTGM-KWACHACRSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Enzyme Assay: The assay uses baculovirus-expressed human cathepsin S and the boc-Val-Leu-Lys-AMC fluorescent substrate available from Bachem in a 384 well plate format, in which 7 test compounds can be tested in parallel with a positive control comprising a known cathepsin S inhibitor comparator. The first test compound prepared in DMSO is added to column 1 of the top row, typically at a volume to provide between 10 and 30 times the initially determined rough K. The rough Ki is calculated from a preliminary run in which 10 μl/well of 1 mM boc-VLK-AMC (1/10 dilution of 10 mM stock in DMSO diluted into assay buffer) is dispensed to rows B to H and 20 μl/well to row A of a 96 well Microfluor plate. 2 μl of each 10 mM test compound is added to a separate well on row A, columns 1-10. Add 90 μl assay buffer containing 1 mM DTT and 2 nM cathepsin S to each well of rows B-H and 180 μl to row A.
Measurement: Ki = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 567.69, ALogP 2.27, HBA 8, HBD 1, PSA 95.08, QED 0.51
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3csc(N4CCN(C)CC4)n3)c(F)c2)[C@@H]2C(=O)CO[C@H]12
InChIKey: RFCUHPQJTGIXFS-GTKJVGNCSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Assay: The enzyme is commercially available human cathepsin L (for example Calbiochem). The substrate is H-D-Val-Leu-Lys-AMC available from Bahcem. The assay buffer is 100 mM sodium acetate 1 mM EDTA, pH5.5) The DMSO stock (10 mM in 100% DMSO) is diluted to 10% in assay buffer. Enzyme is prepared at 5 nM concentration in assay buffer plus 1 mM dithiothreitol just before use. 2 ul of 10 mM inhibitor made up in 100% DMSO is dispensed into row A. 10 μl of 50 μM substrate (=1/200 dilution of 10 mM stock in DMSO, diluted in assay buffer).
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 567.69, ALogP 2.27, HBA 8, HBD 1, PSA 95.08, QED 0.51
Compound (SMILES): CC(C)=C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3nc(N4CCN(C)CC4)sc3F)cc2)[C@@H]2C(=O)CO[C@H]12
InChIKey: UTDIUZBVSSNGOU-QGNCETNGSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Enzyme Assay: The assay uses baculovirus-expressed human cathepsin S and the boc-Val-Leu-Lys-AMC fluorescent substrate available from Bachem in a 384 well plate format, in which 7 test compounds can be tested in parallel with a positive control comprising a known cathepsin S inhibitor comparator. The first test compound prepared in DMSO is added to column 1 of the top row, typically at a volume to provide between 10 and 30 times the initially determined rough K. The rough Ki is calculated from a preliminary run in which 10 μl/well of 1 mM boc-VLK-AMC (1/10 dilution of 10 mM stock in DMSO diluted into assay buffer) is dispensed to rows B to H and 20 μl/well to row A of a 96 well Microfluor plate. 2 μl of each 10 mM test compound is added to a separate well on row A, columns 1-10. Add 90 μl assay buffer containing 1 mM DTT and 2 nM cathepsin S to each well of rows B-H and 180 μl to row A.
Measurement: Ki = 14500 nM (pChEMBL 4.840000152587891)
Descriptors: MW 597.76, ALogP 3.61, HBA 8, HBD 1, PSA 95.08, QED 0.46
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@@H](NC(=O)c2ccc(-c3nc(N4CCN(C)CC4)sc3F)cc2)C2CCCC2)[C@@H]2C(=O)CO[C@H]12
InChIKey: DEMUCOOCKQGXOE-SXEIHZRZSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Enzyme Assay: Standard assay conditions for the determination of kinetic constants used a fluorogenic peptide substrate, typically H-D-Ala-Leu-Lys-AMC, and were determined in either 100 mM Mes/Tris, pH 7.0 containing 1 mM EDTA and 10 mM 2-mercaptoethanol or 100 mM Na phosphate, imM EDTA, 0.1% PEG4000 pH 6.5 or 100 mM Na acetate, pH 5.5 containing 5 mM EDTA and 20 mM cysteine, in each case optionally with 1M DTT as stabiliser. The enzyme concentration used was 5 nM. The stock substrate solution was prepared at 10 mM in DMSO. Screens were carried out at a fixed substrate concentration of 60 μM and detailed kinetic studies with doubling dilutions of substrate from 250 μM. The total DMSO concentration in the assay was kept below 3%. All assays were conducted at ambient temperature. Product fluorescence (excitation at 390 nm, emission at 460 nm) was monitored with a Labsystems Fluoroskan Ascent fluorescent plate reader.
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 579.7, ALogP 2.42, HBA 8, HBD 1, PSA 95.08, QED 0.53
Compound (SMILES): Fc1cnc2[nH]nc(Nc3cc(C(F)(F)F)cc(-c4ccccc4Cl)n3)c2c1
InChIKey: GBGNHUZQFPYZRM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 407.76, ALogP 5.57, HBA 4, HBD 2, PSA 66.49, QED 0.44
Compound (SMILES): Cc1cc(Nc2n[nH]c3ncc(F)cc23)nc(-c2ccccc2Cl)c1C
InChIKey: MVUKVIIMDNACQW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 367.82, ALogP 5.17, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): Cc1cc(Nc2n[nH]c3ncc(F)cc23)nc(-c2ccccc2Cl)c1
InChIKey: QAFFAZAVQKPMKM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 353.79, ALogP 4.86, HBA 4, HBD 2, PSA 66.49, QED 0.55
Compound (SMILES): Cc1cc(-c2ccccc2Cl)nc(Nc2n[nH]c3ncc(F)cc23)c1C
InChIKey: ZHZPUYSNZQKXRF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 367.82, ALogP 5.17, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): Cc1cc(Nc2n[nH]c3ncc(F)cc23)nc(-c2ccccc2)c1C
InChIKey: RAUNAZYXRMQIJT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 333.37, ALogP 4.52, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): CCC(CC)n1ncc2c(=O)[nH]c(CC3CCCCC3)nc21
InChIKey: GXWSVMJGLJNVHK-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 302.42, ALogP 3.6, HBA 4, HBD 1, PSA 63.57, QED 0.92
Compound (SMILES): CCOc1cc(C2=NC(=O)NC(c3cccnc3)C2c2ccsc2)cc([N+](=O)[O-])c1O
InChIKey: CKPKDXIVCGGHEH-UHFFFAOYSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 438.47, ALogP 4.19, HBA 7, HBD 2, PSA 126.95, QED 0.44
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)NS(=O)(=O)C6(C)CC6)C[C@H]5/C=C\CCCCN(C)C(=O)[C@@H]4C3)cc(-c3nc(C(C)C)cs3)nc2c1Cl
InChIKey: LYPMUUHUNIGEOB-OTVJIGPHSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic Assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate,Â  Ac-DED(Edans)EEAbuÃ[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ã¢ Â«ke Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348].
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 784.4, ALogP 5.99, HBA 10, HBD 2, PSA 156.89, QED 0.26
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)NS(=O)(=O)C6(C)CC6)C[C@H]5/C=C\CCCCN(C)C(=O)[C@@H]4C3)cc(-c3nc(C(C)C)cs3)nc2c1C
InChIKey: CVFQOKIBZTWREC-UDWBKMJLSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic Assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate,Â  Ac-DED(Edans)EEAbuÃ[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ã¢ Â«ke Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348].
Measurement: Ki = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 763.98, ALogP 5.64, HBA 10, HBD 2, PSA 156.89, QED 0.28
Compound (SMILES): Cc1cc(C(N)=O)ccc1-n1nc(C(C)C)c2c(-n3cnc(-c4cnn(C)c4)c3)ccnc21
InChIKey: JZYLVXOKNXFKFF-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of biotin-labeled geldanamycin from His-tagged HSP90alpha NTD (unknown origin) preincubated for 2 hrs followed by biotin-labeled geldanamycin addition and measured after 1 hr by AlphaScreen assay
Measurement: IC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 440.51, ALogP 3.54, HBA 8, HBD 1, PSA 109.44, QED 0.45
Compound (SMILES): CCc1cc(C(N)=O)ccc1-n1nc(C(C)C)c2c(-n3cnc(-c4cnn(C)c4)c3)ccnc21
InChIKey: NVVPMZUGELHVMH-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Inhibition of human recombinant HSP90beta expressed in Escherichia coli BL21 (DE3) incubated for 12 hrs
Measurement: IC50 = 21.3 nM (pChEMBL 7.670000076293945)
Descriptors: MW 454.54, ALogP 3.79, HBA 8, HBD 1, PSA 109.44, QED 0.42
Compound (SMILES): CNc1cc(-n2nc(C(C)C)c3c(-n4cnc(-c5cnn(C)c5)c4)ccnc32)ccc1C(N)=O
InChIKey: UDFYSCOICYFDQS-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of biotin-labeled geldanamycin from His-tagged HSP90alpha NTD (unknown origin) preincubated for 2 hrs followed by biotin-labeled geldanamycin addition and measured after 1 hr by AlphaScreen assay
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 455.53, ALogP 3.27, HBA 9, HBD 2, PSA 121.47, QED 0.41
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccccc4)c3c2)ccc1O
InChIKey: ZYIVFBQMIVATBO-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 2150 nM (pChEMBL 5.670000076293945)
Descriptors: MW 343.39, ALogP 4.75, HBA 5, HBD 2, PSA 67.27, QED 0.56
Compound (SMILES): Oc1ccc(-c2ccc3ncnc(Nc4ccccc4)c3c2)cc1
InChIKey: PEIOQGQNZUURLI-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 9456 nM (pChEMBL 5.019999980926514)
Descriptors: MW 313.36, ALogP 4.75, HBA 4, HBD 2, PSA 58.04, QED 0.57
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4cccc(O)c4)c3c2)ccc1O
InChIKey: LXUOHVWXSIYKFA-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 359.39, ALogP 4.46, HBA 6, HBD 3, PSA 87.5, QED 0.5
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(F)c(Cl)c4)c3c2)ccc1O
InChIKey: GCIMOXRJCCJFHE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 1014 nM (pChEMBL 5.989999771118164)
Descriptors: MW 395.82, ALogP 5.55, HBA 5, HBD 2, PSA 67.27, QED 0.47
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(F)cc4)c3c2)ccc1O
InChIKey: UXJNJXDYBPWNOB-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 1452 nM (pChEMBL 5.840000152587891)
Descriptors: MW 361.38, ALogP 4.89, HBA 5, HBD 2, PSA 67.27, QED 0.54
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(Cl)cc4F)c3c2)ccc1O
InChIKey: YNUOKJQLMFJASA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 817.2 nM (pChEMBL 6.090000152587891)
Descriptors: MW 395.82, ALogP 5.55, HBA 5, HBD 2, PSA 67.27, QED 0.47
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(C)cc4F)c3c2)ccc1O
InChIKey: CNDJHJOZDIWJPS-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 1906 nM (pChEMBL 5.71999979019165)
Descriptors: MW 375.4, ALogP 5.2, HBA 5, HBD 2, PSA 67.27, QED 0.51
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4cccc(C(F)(F)F)c4)c3c2)ccc1O
InChIKey: QSRJUWTVHOQBPZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 1169 nM (pChEMBL 5.929999828338623)
Descriptors: MW 411.38, ALogP 5.77, HBA 5, HBD 2, PSA 67.27, QED 0.45
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(O)cc4)c3c2)ccc1O
InChIKey: YVGALQKPXFBOSA-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 503.2 nM (pChEMBL 6.300000190734863)
Descriptors: MW 359.39, ALogP 4.46, HBA 6, HBD 3, PSA 87.5, QED 0.47
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(F)cc4F)c3c2)ccc1O
InChIKey: YUERBQPSJHOKJZ-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 882.1 nM (pChEMBL 6.050000190734863)
Descriptors: MW 379.37, ALogP 5.03, HBA 5, HBD 2, PSA 67.27, QED 0.52
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(Cl)cc4O)c3c2)ccc1O
InChIKey: YITYQFMKMIKUEV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 1357 nM (pChEMBL 5.869999885559082)
Descriptors: MW 393.83, ALogP 5.11, HBA 6, HBD 3, PSA 87.5, QED 0.42
Compound (SMILES): COc1cccc(Nc2ncnc3ccc(-c4ccc(O)c(OC)c4)cc23)c1
InChIKey: SEOLDYFMKMKGLS-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 1386 nM (pChEMBL 5.860000133514404)
Descriptors: MW 373.41, ALogP 4.76, HBA 6, HBD 2, PSA 76.5, QED 0.53