lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCc2ccc(C(=O)NO)cc2)c2cccnc2)cc1
InChIKey: CZIFWUIZPKVGJZ-FYJGNVAPSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 419.51, ALogP 3.78, HBA 5, HBD 3, PSA 91.32, QED 0.23
Compound (SMILES): COc1ccc(/C(=C\c2ccc(SC)cc2)C(=O)NCc2ccc(C(=O)NO)cc2)cc1
InChIKey: GONUDRZNKYWMTF-HZHRSRAPSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 448.54, ALogP 4.39, HBA 5, HBD 3, PSA 87.66, QED 0.16
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCc2ccc(C(=O)NO)cc2)c2ccc(C)cc2)cc1
InChIKey: YBBUTNCCBNQBFY-HZHRSRAPSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 432.55, ALogP 4.69, HBA 4, HBD 3, PSA 78.43, QED 0.17
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCc2ccc(C(=O)NO)cc2)c2ccsc2)cc1
InChIKey: ZYOVDHXSZVBINT-UDWIEESQSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 424.55, ALogP 4.45, HBA 5, HBD 3, PSA 78.43, QED 0.23
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCc2ccc(/C=C/C(=O)NO)cc2)c2ccc(F)cc2)cc1
InChIKey: DVHRFNSGDJIRSJ-SQTMOLFMSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 462.55, ALogP 4.92, HBA 4, HBD 3, PSA 78.43, QED 0.15
Compound (SMILES): COc1ccc(/C=C(/C(=O)NCc2ccc(/C=C/C(=O)NO)cc2)c2ccc(F)cc2)cc1OC
InChIKey: DBTQBONKZBXAAE-QLOONLQOSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 476.5, ALogP 4.22, HBA 5, HBD 3, PSA 96.89, QED 0.19
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCCCCCCC(=O)NO)c2ccc(F)cc2)cc1
InChIKey: UWOLQCFZNNRZKN-LTGZKZEYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 430.55, ALogP 4.66, HBA 4, HBD 3, PSA 78.43, QED 0.12
Compound (SMILES): O=C(CCCCCCNC(=O)/C(=C\c1ccccc1)c1ccccc1)NO
InChIKey: MUZGPCWQKJHVLR-JZJYNLBNSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 366.46, ALogP 3.8, HBA 3, HBD 3, PSA 78.43, QED 0.2
Compound (SMILES): O=C(CCCCCNC(=O)/C(=C/c1c(F)cc(F)cc1F)c1ccc(F)cc1)NO
InChIKey: NDVGLZIKCDJIEM-FOWTUZBSSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 424.39, ALogP 3.97, HBA 3, HBD 3, PSA 78.43, QED 0.14
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCCCCCC(=O)NO)c2ccsc2)cc1
InChIKey: WPWCCFZTJJLWKB-QGOAFFKASA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 404.56, ALogP 4.19, HBA 5, HBD 3, PSA 78.43, QED 0.18
Compound (SMILES): COc1ccc(/C(=C\c2ccc(SC)cc2)C(=O)NCCCCCC(=O)NO)cc1
InChIKey: YGGGXDOBLIHUOI-LTGZKZEYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 428.55, ALogP 4.14, HBA 5, HBD 3, PSA 87.66, QED 0.13
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCCCCCC(=O)NO)c2ccccc2F)cc1
InChIKey: XOAGOYIMFGCCNF-XDJHFCHBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 416.52, ALogP 4.27, HBA 4, HBD 3, PSA 78.43, QED 0.13
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCCCCCC(=O)NO)c2ccccc2Cl)cc1
InChIKey: KDMAIKWJAWTIIF-XDJHFCHBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 432.97, ALogP 4.78, HBA 4, HBD 3, PSA 78.43, QED 0.13
Compound (SMILES): CSc1ccc(/C=C(/C(=O)NCCCCCC(=O)NO)c2ccc(C)cc2)cc1
InChIKey: SDHGLBIWGCIVEB-LTGZKZEYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 412.56, ALogP 4.44, HBA 4, HBD 3, PSA 78.43, QED 0.13
Compound (SMILES): O=C(CCCCCNC(=O)NC(=O)/C(=C/c1ccccc1)c1ccccc1)NO
InChIKey: YBCCWUFALLZBCH-KNTRCKAVSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: HDAC Inhbition Assay: Assay was done in 96-well black microplate and total volume of the assay was 100 pt. Mouse liver enzyme (10 mg/ml) was diluted 1:6 with HDAC buffer. Enzyme cocktail was made of 10 μL of diluted enzyme and 30 μL of HDAC buffer. 40 μl of enzyme cocktail followed by 10 μL of test compound (1 μM and 10 μM) or buffer (control) was added to each well. The plate was pre-incubated at 37° C. for 5 minutes. The HDAC reaction was started by adding 50 μl of HDAC substrate Boc-Lys (Ac)-AMC (Bachem AG, Switzerland). The plate was incubated at 37° C. for 30 min. The reaction was stopped by adding 100 μL, of Trypsin stop solution and incubating at 37° C. for 15-30 min. Measuring the fluorescence at excitation wavelength of 360 nm and emission wavelength of 460 nm monitored the release of AMC. Buffer alone and substrate alone served as blank.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 395.46, ALogP 3.12, HBA 4, HBD 4, PSA 107.53, QED 0.17
Compound (SMILES): N#Cc1sc(NCCNc2nc(-c3ccc(Cl)cc3Cl)cn3ccnc23)nc1N
InChIKey: ZQLAWFSNBMZAAZ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 445.34, ALogP 4.14, HBA 9, HBD 3, PSA 116.95, QED 0.38
Compound (SMILES): N#Cc1ccc(NCCNc2nc(-c3ccc(Cl)cc3Cl)cn3nc(C(=O)O)cc23)nc1
InChIKey: CWBGUJMDPNTSTJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 468.3, ALogP 4.19, HBA 8, HBD 3, PSA 128.23, QED 0.34
Compound (SMILES): CN1CCN(CCNC(=O)c2cc3c(NCCNc4ccc(C#N)cn4)nc(-c4ccc(Cl)cc4Cl)cn3n2)CC1
InChIKey: XPXISBBLUNSHKM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 593.52, ALogP 3.47, HBA 10, HBD 3, PSA 126.51, QED 0.24
Compound (SMILES): Cc1nc(C)n2nc(-c3ccccc3)nc(NCCNc3ccc(C#N)cn3)c12
InChIKey: VVNOBFBZOPLADT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 384.45, ALogP 3.2, HBA 8, HBD 2, PSA 103.82, QED 0.49
Compound (SMILES): CCOC(=O)c1cc2c(N3CCCC(Nc4nc(N)c(C(C)=O)s4)C3)nc(-c3ccc(Cl)cc3Cl)cn2n1
InChIKey: AVTOVEHAOIIEJE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 574.49, ALogP 5.2, HBA 11, HBD 2, PSA 127.74, QED 0.23
Compound (SMILES): N#Cc1sc(NC2CCCN(c3nc(-c4ccc(Cl)cc4Cl)cn4nc(C(=O)O)cc34)C2)nc1N
InChIKey: VLUFCCGODLLKEF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 529.41, ALogP 4.39, HBA 10, HBD 3, PSA 145.46, QED 0.34
Compound (SMILES): N#Cc1sc(NCCNc2nc(-c3ccc(Cl)cc3Cl)cn3nc(C(=O)NCC(=O)O)cc23)nc1N
InChIKey: GLINRRWQUGILKI-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 546.4, ALogP 2.95, HBA 11, HBD 5, PSA 183.35, QED 0.2
Compound (SMILES): N#Cc1ccc(NCCNc2nc(-c3ccc(Cl)cc3Cl)cn3nc(CNC4CC4)cc23)nc1
InChIKey: QGLRWBKXHAWGEQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Biochemical Assay: The ingredients required for this purpose are mixed in a black 384-well microtiter plate with transparent base (from Greiner, catalog number 781092). The requirements in this connection for each well of the 384-well microtiter plate are 5 nM GSK3β (from Upstate, catalog number xy), 40 μM GSK3β substrate GSM (sequence H-RRRPASVPPSPSLSRHS-(pS)-HQRR, from Upstate, catalog number 2-533), 30 μM nicotinamide adenine dinucleotide NADH (Roche Diagnostics, catalog number 10107735), 50 μM adenosine triphosphate ATP (from Sigma, catalog number A7966) and 2 mM phosphoenolpyruvate (from Roche, catalog number 128112). The required reaction buffer in which the biochemical reaction takes place consists of 50 mM Trizma hydrochloride Tris-HCl pH: 7.5 (from Sigma, catalog number T3253), 5 mM magnesium chloride MgCl2 (from Sigma, catalog number M8266), 0.2 mM DL-dithiothreitol DTT (from Sigma, catalog number D9779), 2 mM ethylenediaminetetraacetic acid EDTA (from Sigma, catalog number E6758), 0.01% Triton X-100 (from Sigma, catalog number T8787) and 0.05% bovine serum albumin BSA (from Sigma, catalog number B4287). Active substances are dissolved in dimethyl sulfoxide DMSO (from Sigma, catalog number D8418) in a concentration of 10 mM. Active substances are added in serial concentrations of 10 μM, 1 μM, 0.1 μM, 0.01 μM, 0.001 μM, 0.0001 μM, 0.00001 μM, 0.000001 μM to the mixtures of the biochemical reaction. As control, dimethyl sulfoxide is added instead of substance in a final concentration of 0.1%. The reaction is incubated at 30° C. for 2 hours and then the resulting fluorescence is measured in a Tecan Safire-XFLUOR4 instrument, version V4.50 (serial number 12901300283) with the specifications: measurement mode−fluorescence measured from below, extinction wavelength 340 nm, emission wavelength 465 nm, slit width extinction 5 nm, slit width emission 5 nm, gain mode 120, delay 0 μs, number of light flashes per measurement 3, and an integration time of 40 μs.
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 493.4, ALogP 4.75, HBA 8, HBD 3, PSA 102.96, QED 0.29
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: COTYYZPYDJKKIS-KQMWNOITSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 4763 nM (pChEMBL 5.320000171661377)
Descriptors: MW 435.57, ALogP 4.62, HBA 5, HBD 1, PSA 75.43, QED 0.76
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCC2)c1=O
InChIKey: YQRPDABJJCVAGZ-ZBYYUNFXSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 451.61, ALogP 5.55, HBA 5, HBD 1, PSA 75.43, QED 0.66
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C23CCCC(CCC2)C3)c1=O
InChIKey: HQRWWKRMPLZJMJ-YHSYXWOYSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 178 nM (pChEMBL 6.75)
Descriptors: MW 435.57, ALogP 4.77, HBA 5, HBD 1, PSA 75.43, QED 0.75
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CCC[C@H]1C[C@@H](n1c(=O)c(C(=O)O)nc4ccccc41)C3)C2
InChIKey: OWAGGONYNCKXDC-PCXLCNFCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 691 nM (pChEMBL 6.159999847412109)
Descriptors: MW 449.6, ALogP 4.87, HBA 5, HBD 1, PSA 75.43, QED 0.72
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCCC2)c1=O
InChIKey: DNQQJKRDKSYDKP-JKHIJQBDSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 1436 nM (pChEMBL 5.840000152587891)
Descriptors: MW 465.64, ALogP 5.94, HBA 5, HBD 1, PSA 75.43, QED 0.61
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: In Vitro Inhibition Assay: Measurements were performed in a reaction volume of 50 μL using 96-well assay plates. Kinase enzyme, inhibitor, ATP (at the Km for the kinase), and 1 μM peptide substrate (Biotin-AVLESEEELYSSARQ-NH2) were incubated in a reaction buffer composed of 20 mM Tris, 50 mM NaCl, MgCl2 (5-25 mM depending on the kinase), MnCl2 (0-10 mM), 1 mM DTT, 0.1 mM EDTA, 0.01% bovine serum albumin, 0.005% Tween-20, and 10% DMSO at pH 7.4 for one hour. The reaction was quenched by the addition of 1.2 equivalents of EDTA (relative to divalent cation) in 25 μL of 1× Lance buffer (Perkin-Elmer). Streptavidin-APC (Perkin-Elmer) and Eu-labeled p-Tyr100 antibody (Perkin-Elmer) in 1× Lance buffer were added in a 25 μL volume to give final concentrations of 100 nM and 2.5 nM, respectively, and the mixture was allowed to incubate for one hour. The TR-FRET signal was measured on a multimode plate reader with an excitation wavelength (πEx) of 330 nm and detection wavelengths (πEm) of 615 and 665 nm. Activity was determined by the ratio of the fluorescence at 665 nm to that at 615 nm. For each compound, enzyme activity was measured at various concentrations of compound. Negative control reactions were performed in the absence of inhibitor in replicates of six, and two no-enzyme controls were used to determine baseline fluorescence levels.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N1CC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: CLXHRDKUVCHURW-KRWDZBQOSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: In Vitro Inhibition Assay: Measurements were performed in a reaction volume of 50 μL using 96-well assay plates. Kinase enzyme, inhibitor, ATP (at the Km for the kinase), and 1 μM peptide substrate (Biotin-AVLESEEELYSSARQ-NH2) were incubated in a reaction buffer composed of 20 mM Tris, 50 mM NaCl, MgCl2 (5-25 mM depending on the kinase), MnCl2 (0-10 mM), 1 mM DTT, 0.1 mM EDTA, 0.01% bovine serum albumin, 0.005% Tween-20, and 10% DMSO at pH 7.4 for one hour. The reaction was quenched by the addition of 1.2 equivalents of EDTA (relative to divalent cation) in 25 μL of 1× Lance buffer (Perkin-Elmer). Streptavidin-APC (Perkin-Elmer) and Eu-labeled p-Tyr100 antibody (Perkin-Elmer) in 1× Lance buffer were added in a 25 μL volume to give final concentrations of 100 nM and 2.5 nM, respectively, and the mixture was allowed to incubate for one hour. The TR-FRET signal was measured on a multimode plate reader with an excitation wavelength (πEx) of 330 nm and detection wavelengths (πEm) of 615 and 665 nm. Activity was determined by the ratio of the fluorescence at 665 nm to that at 615 nm. For each compound, enzyme activity was measured at various concentrations of compound. Negative control reactions were performed in the absence of inhibitor in replicates of six, and two no-enzyme controls were used to determine baseline fluorescence levels.
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 426.48, ALogP 3.83, HBA 7, HBD 1, PSA 99.16, QED 0.49
Compound (SMILES): C=CC(=O)N1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: CLXHRDKUVCHURW-QGZVFWFLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: In Vitro Inhibition Assay: Measurements were performed in a reaction volume of 50 μL using 96-well assay plates. Kinase enzyme, inhibitor, ATP (at the Km for the kinase), and 1 μM peptide substrate (Biotin-AVLESEEELYSSARQ-NH2) were incubated in a reaction buffer composed of 20 mM Tris, 50 mM NaCl, MgCl2 (5-25 mM depending on the kinase), MnCl2 (0-10 mM), 1 mM DTT, 0.1 mM EDTA, 0.01% bovine serum albumin, 0.005% Tween-20, and 10% DMSO at pH 7.4 for one hour. The reaction was quenched by the addition of 1.2 equivalents of EDTA (relative to divalent cation) in 25 μL of 1× Lance buffer (Perkin-Elmer). Streptavidin-APC (Perkin-Elmer) and Eu-labeled p-Tyr100 antibody (Perkin-Elmer) in 1× Lance buffer were added in a 25 μL volume to give final concentrations of 100 nM and 2.5 nM, respectively, and the mixture was allowed to incubate for one hour. The TR-FRET signal was measured on a multimode plate reader with an excitation wavelength (πEx) of 330 nm and detection wavelengths (πEm) of 615 and 665 nm. Activity was determined by the ratio of the fluorescence at 665 nm to that at 615 nm. For each compound, enzyme activity was measured at various concentrations of compound. Negative control reactions were performed in the absence of inhibitor in replicates of six, and two no-enzyme controls were used to determine baseline fluorescence levels.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 426.48, ALogP 3.83, HBA 7, HBD 1, PSA 99.16, QED 0.49