lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ncc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)cc1-c1cccc(C#N)c1
InChIKey: IRVFGWCULVQEEU-FQEVSTJZSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.87, ALogP 4.23, HBA 5, HBD 2, PSA 112.31, QED 0.57
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1ccncc1
InChIKey: HROZEYIDCUMKKM-KRWDZBQOSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 8040 nM (pChEMBL 5.090000152587891)
Descriptors: MW 411.85, ALogP 3.75, HBA 5, HBD 2, PSA 101.41, QED 0.61
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1ccc(F)nc1
InChIKey: NXWMTUVFGFPHPU-INIZCTEOSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 6490 nM (pChEMBL 5.190000057220459)
Descriptors: MW 429.84, ALogP 3.89, HBA 5, HBD 2, PSA 101.41, QED 0.55
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1cccnc1OC
InChIKey: MVXMJDSAYZSIDL-KRWDZBQOSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 441.87, ALogP 3.76, HBA 6, HBD 2, PSA 110.64, QED 0.55
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2C)nc1-c1cccnc1OC
InChIKey: KLZXJOMGKQMSAD-SFHVURJKSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 347 nM (pChEMBL 6.460000038146973)
Descriptors: MW 421.45, ALogP 3.42, HBA 6, HBD 2, PSA 110.64, QED 0.57
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2C)nc1-c1cc(C)cnc1Cl
InChIKey: HVIWEBKCGZWHMC-SFHVURJKSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 5630 nM (pChEMBL 5.25)
Descriptors: MW 439.9, ALogP 4.37, HBA 5, HBD 2, PSA 101.41, QED 0.53
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2C)nc1-c1cc(C)ncc1F
InChIKey: MTSWQBRGBADNCL-IBGZPJMESA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 118.2 nM (pChEMBL 6.929999828338623)
Descriptors: MW 423.44, ALogP 3.85, HBA 5, HBD 2, PSA 101.41, QED 0.6
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1cc(C)cnc1Cl
InChIKey: FXGXCROVEVXOIR-KRWDZBQOSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 8770 nM (pChEMBL 5.059999942779541)
Descriptors: MW 460.32, ALogP 4.71, HBA 5, HBD 2, PSA 101.41, QED 0.5
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1ccncc1F
InChIKey: XOAROKCNONOQLY-KRWDZBQOSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 115.3 nM (pChEMBL 6.940000057220459)
Descriptors: MW 429.84, ALogP 3.89, HBA 5, HBD 2, PSA 101.41, QED 0.59
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1cc(C)nc(N2CCOCC2)c1
InChIKey: APKBECMTWRUJES-NRFANRHFSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 9080 nM (pChEMBL 5.039999961853027)
Descriptors: MW 510.98, ALogP 3.9, HBA 7, HBD 2, PSA 113.88, QED 0.47
Compound (SMILES): Cc1ccccc1[C@H](CC(=O)O)NC(=O)C1=CC=NC(N2CCCCC2)C1
InChIKey: XLIWANCJXZCUII-OYKVQYDMSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 369.47, ALogP 2.84, HBA 4, HBD 2, PSA 82, QED 0.81
Compound (SMILES): C#CCN(C)Cc1ccc(OC)c2ncccc12
InChIKey: JIZLGBAUPUQKRV-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition Assay: MAO-A and MAO-B activity was measured using radioactive substrates. The substrate for MAO-A was 5 HT and for MAO-B was PEA. When measuring the activity of MAO-A, the MAO-B activity was inhibited with deprenyl and when measuring the activity of MAO-B the activity of MAO-A was inhibited with clorgylin. Blank samples were produced using TCP to inhibit both of the enzymes. The metabolites were extracted to toluene and read in a β -counter. The results are expressed in relative activity and normalized to the amount of protein in the tissue. Figs. 1 and 2 show MAO-A/MAO-B activity of compounds 3, 4 and of 0-Methyl-M3O at various concentrations (10 -"5 -10 -"8 ). As presented in Figs. 1 and 2, it can be seen that compounds 3, 4 and 0-Methyl-M3O were all potent inhibitors of MAO-A and MAO-B extracted from rat brain, compound 3 clearly the most potent inhibitor of the three compounds.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 240.31, ALogP 2.31, HBA 3, HBD 0, PSA 25.36, QED 0.77
Compound (SMILES): C#CCN(C)CCc1ccc(O)c2ncccc12
InChIKey: KDAUAZRWYCHDFB-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition Assay: MAO-A and MAO-B activity was measured using radioactive substrates. The substrate for MAO-A was 5 HT and for MAO-B was PEA. When measuring the activity of MAO-A, the MAO-B activity was inhibited with deprenyl and when measuring the activity of MAO-B the activity of MAO-A was inhibited with clorgylin. Blank samples were produced using TCP to inhibit both of the enzymes. The metabolites were extracted to toluene and read in a β -counter. The results are expressed in relative activity and normalized to the amount of protein in the tissue. Figs. 1 and 2 show MAO-A/MAO-B activity of compounds 3, 4 and of 0-Methyl-M3O at various concentrations (10 -"5 -10 -"8 ). As presented in Figs. 1 and 2, it can be seen that compounds 3, 4 and 0-Methyl-M3O were all potent inhibitors of MAO-A and MAO-B extracted from rat brain, compound 3 clearly the most potent inhibitor of the three compounds.
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 240.31, ALogP 2.05, HBA 3, HBD 1, PSA 36.36, QED 0.83
Compound (SMILES): C#CCN(C)CCCc1ccc(O)c2ncccc12
InChIKey: HBFPRSLXKQRTJR-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition Assay: MAO-A and MAO-B activity was measured using radioactive substrates. The substrate for MAO-A was 5 HT and for MAO-B was PEA. When measuring the activity of MAO-A, the MAO-B activity was inhibited with deprenyl and when measuring the activity of MAO-B the activity of MAO-A was inhibited with clorgylin. Blank samples were produced using TCP to inhibit both of the enzymes. The metabolites were extracted to toluene and read in a β -counter. The results are expressed in relative activity and normalized to the amount of protein in the tissue. Figs. 1 and 2 show MAO-A/MAO-B activity of compounds 3, 4 and of 0-Methyl-M3O at various concentrations (10 -"5 -10 -"8 ). As presented in Figs. 1 and 2, it can be seen that compounds 3, 4 and 0-Methyl-M3O were all potent inhibitors of MAO-A and MAO-B extracted from rat brain, compound 3 clearly the most potent inhibitor of the three compounds.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 254.33, ALogP 2.44, HBA 3, HBD 1, PSA 36.36, QED 0.83
Compound (SMILES): Oc1cccc(Nc2nc(-c3ccccn3)cs2)c1
InChIKey: GIGNWEDIMLUWCT-UHFFFAOYSA-N
Target: Methyl-CpG-binding domain protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBB5
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 1550 nM (pChEMBL 5.809999942779541)
Descriptors: MW 269.33, ALogP 3.65, HBA 5, HBD 2, PSA 58.04, QED 0.76
Compound (SMILES): Cn1c2ccccc2n2cc(-c3ccc([N+](=O)[O-])cc3)nc12
InChIKey: IBVRCTVMEOHDDP-UHFFFAOYSA-N
Target: Methyl-CpG-binding domain protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBB5
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 6140 nM (pChEMBL 5.210000038146973)
Descriptors: MW 292.3, ALogP 3.4, HBA 5, HBD 0, PSA 65.37, QED 0.42
Compound (SMILES): Oc1ccc(C2NN=C(c3ccccc3)S2)cc1
InChIKey: UAYJSAALHQXXRV-UHFFFAOYSA-N
Target: Methyl-CpG-binding domain protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBB5
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 256.33, ALogP 3.09, HBA 4, HBD 2, PSA 44.62, QED 0.87
Compound (SMILES): COc1cc(O)cc(Br)c1/C=N/Nc1nc2ccccc2s1
InChIKey: CAYPYIUGJJUJJP-CAOOACKPSA-N
Target: Methyl-CpG-binding domain protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBB5
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 378.25, ALogP 4.22, HBA 6, HBD 2, PSA 66.74, QED 0.53
Compound (SMILES): OC1(C(F)(F)F)CC(c2ccccc2)=NN1C(=S)c1ccccc1
InChIKey: RIANETHNVIQQBE-UHFFFAOYSA-N
Target: Methyl-CpG-binding domain protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBB5
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 350.37, ALogP 3.72, HBA 3, HBD 1, PSA 35.83, QED 0.84
Compound (SMILES): Clc1ccc(C2NN=C(c3ccccc3)S2)cc1
InChIKey: FJPCKWLGUUDTOP-UHFFFAOYSA-N
Target: Methyl-CpG-binding protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51608
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 33900 nM (pChEMBL 4.46999979019165)
Descriptors: MW 274.78, ALogP 4.04, HBA 3, HBD 1, PSA 24.39, QED 0.89
Compound (SMILES): Nc1cccc(-c2nnc(-c3ccccc3)o2)c1
InChIKey: DOYLAQBXDHFRFB-UHFFFAOYSA-N
Target: Methyl-CpG-binding protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51608
Assay: Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers containing BamHI and EcoRI recognition sites (5'-GGATCCATGGAGAGCGGGAAGAGGATGGA-3' (SEQ ID NO:1) and 5'-GAATTCCATCTTTCCAGTTCTGAAGT-3' (SEQ ID NO:2)), and then introduced into pFBC6H, a modified pFastBac-1 baculovirus expression vector (Invitrogen), that had been linearized via cutting with EcoRI and XbaI. This pFB6H-MBD2 expression construct was used to transform DH10BacE. coli competent cells (Invitrogen) to form an MBD2 expression bacmid via site-specific transposition. The MBD2 expression bacmid was then transfected into Sf9 insect cells for production of recombinant MBD2 baculovirus particles, which were used to infect Sf9 cells (1 MOI, 48 hours) to generate recombinant MBD2 protein.
Measurement: IC50 = 8590 nM (pChEMBL 5.070000171661377)
Descriptors: MW 237.26, ALogP 2.99, HBA 4, HBD 1, PSA 64.94, QED 0.7
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CCO1
InChIKey: VXKBREQCYRAEHY-XUDSTZEESA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 312.45, ALogP 4.45, HBA 2, HBD 0, PSA 26.3, QED 0.62
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCC(C)(O)CC3)cn2)cs1)C(F)(F)F
InChIKey: MQGKAHLKCUKYGG-HNNXBMFYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 587.63, ALogP 4.59, HBA 11, HBD 2, PSA 126.88, QED 0.32
Compound (SMILES): CC1(O)CCN(c2cnc(C(=O)Nc3csc(-c4nncn4C4CC4)n3)cc2-n2cnc(C3CC3)c2)CC1
InChIKey: RUURFQLAXJBZCK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 531.65, ALogP 3.8, HBA 11, HBD 2, PSA 126.88, QED 0.37
Compound (SMILES): C[C@H](n1cnnc1-c1nc(NC(=O)c2cc(-n3cnc(C4CC4)c3)c(N3CCN(C)CC3)cn2)cs1)C(F)(F)F
InChIKey: GQWUPQVHSCGKAI-HNNXBMFYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 572.62, ALogP 3.99, HBA 11, HBD 1, PSA 109.89, QED 0.35
Compound (SMILES): CN1CCN(c2cnc(C(=O)Nc3csc(-c4nncn4C4CC4)n3)cc2-n2cnc(C3CC3)c2)CC1
InChIKey: LOMLIMUWYBHJOK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 516.64, ALogP 3.2, HBA 11, HBD 1, PSA 109.89, QED 0.4
Compound (SMILES): O=C1CCc2cc(/C=C/C(=O)N3CCCC(COc4ccc(F)cc4)C3)cnc2N1
InChIKey: REHFYEUIPVRHDS-XCVCLJGOSA-N
Target: Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q6GI75
Assay: Fluorescence Based Assay: The assay buffer "AB" contained 50 mM ADA (N-(2-acetamido)iminodiacetic acid monosodium salt) pH 6.5, 1 mM dithiothreitol, 0.006% Triton-X100 and 50 mM NaCl. The following components are added in a white polystyrene Costar plate (Ref 3912) up to a final volume of 55.5 uL: 1.5 uL DMSO or inhibitor dissolved in DMSO and 54 uL of a FabI/NADPH/NADP+ mixture in AB. After 60 min of pre-incubation at room temperature, the reaction is started by addition of 5 uL of trans-2-octenoyl N-acetylcysteamine thioester (t-o-NAC) to a final volume of 60.5 uL. This reaction mixture is then composed of 2 nM FabI, 40 uM NADPH (Sigma, N7505), 10 uM NADP+(Sigma, N5755), 100 uM t-O-NAC and compound at defined concentration. Fluorescence intensity of NADPH (lamda=ex=360 nm, lamda=em=520 nm) is measured immediately after t-O-NAC addition (T0), and approximately 50 min later (T50) by a Fluostar Optima (BMG) so as to achieve ~30% of NADPH conversion.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 409.46, ALogP 3.44, HBA 4, HBD 1, PSA 71.53, QED 0.77
Compound (SMILES): Cc1nc(C2CN(C(=O)/C=C/c3cnc4c(c3)CCC(=O)N4)C2)no1
InChIKey: JCULLUDCSGOFBT-GORDUTHDSA-N
Target: Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q6GI75
Assay: Fluorescence Based Assay: The assay buffer "AB" contained 50 mM ADA (N-(2-acetamido)iminodiacetic acid monosodium salt) pH 6.5, 1 mM dithiothreitol, 0.006% Triton-X100 and 50 mM NaCl. The following components are added in a white polystyrene Costar plate (Ref 3912) up to a final volume of 55.5 uL: 1.5 uL DMSO or inhibitor dissolved in DMSO and 54 uL of a FabI/NADPH/NADP+ mixture in AB. After 60 min of pre-incubation at room temperature, the reaction is started by addition of 5 uL of trans-2-octenoyl N-acetylcysteamine thioester (t-o-NAC) to a final volume of 60.5 uL. This reaction mixture is then composed of 2 nM FabI, 40 uM NADPH (Sigma, N7505), 10 uM NADP+(Sigma, N5755), 100 uM t-O-NAC and compound at defined concentration. Fluorescence intensity of NADPH (lamda=ex=360 nm, lamda=em=520 nm) is measured immediately after t-O-NAC addition (T0), and approximately 50 min later (T50) by a Fluostar Optima (BMG) so as to achieve ~30% of NADPH conversion.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 339.36, ALogP 1.3, HBA 6, HBD 1, PSA 101.22, QED 0.85
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C(F)(F)F)c1c2=O
InChIKey: OICPOZZKXXBDTD-CYBMUJFWSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin) preincubated for 20 mins followed by Gly-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 479.44, ALogP 1.7, HBA 8, HBD 1, PSA 102.28, QED 0.57
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3ccccc3C#N)c1c2=O
InChIKey: PNGZLJFKFMSBJO-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay: DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37 C. The 30 ul assay solution contained 20 pM recombinant human DPP4 and 50 uM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37 C. prior to start of the experiment. Test compounds were serially diluted (3-fold) in 100% DMSO to avoid solubility issues; working solutions in 3% DMSO were prepared using assay buffer. 10 ul each of enzyme and compound solutions were mixed and pre-incubated at 37 C. for 30 minutes.
Measurement: IC50 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 418.46, ALogP 0.42, HBA 9, HBD 1, PSA 126.07, QED 0.65
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3F)c1c2=O
InChIKey: YAWOUZPWJKYFDX-CYBMUJFWSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay: DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37 C. The 30 ul assay solution contained 20 pM recombinant human DPP4 and 50 uM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37 C. prior to start of the experiment. Test compounds were serially diluted (3-fold) in 100% DMSO to avoid solubility issues; working solutions in 3% DMSO were prepared using assay buffer. 10 ul each of enzyme and compound solutions were mixed and pre-incubated at 37 C. for 30 minutes.
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 429.43, ALogP 0.82, HBA 8, HBD 1, PSA 102.28, QED 0.66
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2nc3n(c(=O)c21)CC(=O)N3C
InChIKey: PPMZXTYNICRHMC-LLVKDONJSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin) preincubated for 20 mins followed by Gly-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 355.4, ALogP -0.48, HBA 8, HBD 1, PSA 102.28, QED 0.73
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](NC(=O)OC(C)(C)C)C3)n(Cc3cc(F)ccc3C#N)c1c2=O
InChIKey: BKMVBDOZLBKNIT-LJQANCHMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay: DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37 C. The 30 ul assay solution contained 20 pM recombinant human DPP4 and 50 uM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37 C. prior to start of the experiment. Test compounds were serially diluted (3-fold) in 100% DMSO to avoid solubility issues; working solutions in 3% DMSO were prepared using assay buffer. 10 ul each of enzyme and compound solutions were mixed and pre-incubated at 37 C. for 30 minutes.
Measurement: IC50 = 13.5 nM (pChEMBL 7.869999885559082)
Descriptors: MW 550.6, ALogP 2.51, HBA 10, HBD 1, PSA 138.38, QED 0.51
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3F)c1c2=O
InChIKey: ULGAIQGMBBLSSH-CQSZACIVSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin) preincubated for 20 mins followed by Gly-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 443.46, ALogP 1.21, HBA 8, HBD 1, PSA 102.28, QED 0.65
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C(F)(F)F)c1c2=O
InChIKey: NHQURNPIJLKKLF-CQSZACIVSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin) preincubated for 20 mins followed by Gly-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 493.47, ALogP 2.09, HBA 8, HBD 1, PSA 102.28, QED 0.56
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C#N)c1c2=O
InChIKey: KMOYVYIQCXEQDG-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay: DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37 C. The 30 ul assay solution contained 20 pM recombinant human DPP4 and 50 uM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37 C. prior to start of the experiment. Test compounds were serially diluted (3-fold) in 100% DMSO to avoid solubility issues; working solutions in 3% DMSO were prepared using assay buffer. 10 ul each of enzyme and compound solutions were mixed and pre-incubated at 37 C. for 30 minutes.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 436.45, ALogP 0.56, HBA 9, HBD 1, PSA 126.07, QED 0.64
Compound (SMILES): OCC(O)c1cccc(-c2ccc(Oc3ccc(C(F)(F)F)cc3)cc2)n1
InChIKey: SEEQNYSKARYQHN-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FLIPR Assay: Recombinant Nav1.7 Cell Line: In vitro assays were performed in a recombinant cell line expressing cDNA encoding the alpha subunit (Nav1.7, SCN9a, PN1, NE) of human Nav1.7 (Accession No. NM__002977). The cell line was provided by investigators at Yale University (Cummins et al, J. Neurosci. 18(23): 9607-9619 (1998)). For dominant selection of the Nav1.7-expressing clones, the expression plasmid co-expressed the neomycin resistance gene. The cell line was constructed in the human embryonic kidney cell line, HEK293, under the influence of the CMV major late promoter, and stable clones were selected using limiting dilution cloning and antibiotic selection using the neomycin analogue, G418. Recombinant beta and gamma subunits were not introduced into this cell line. Additional cell lines expressing recombinant Nav1.7 cloned from other species can also be used, alone or in combination with various beta subunits, gamma subunits or chaperones.Non-Recombinant Cell Lines Expressing Native Nav1.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 375.35, ALogP 4.59, HBA 4, HBD 2, PSA 62.58, QED 0.68
Compound (SMILES): OC[C@@H](O)c1cccc(-c2ccc(Oc3ccc(C(F)(F)F)cc3)cc2)n1
InChIKey: SEEQNYSKARYQHN-LJQANCHMSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FLIPR Assay: Recombinant Nav1.7 Cell Line: In vitro assays were performed in a recombinant cell line expressing cDNA encoding the alpha subunit (Nav1.7, SCN9a, PN1, NE) of human Nav1.7 (Accession No. NM__002977). The cell line was provided by investigators at Yale University (Cummins et al, J. Neurosci. 18(23): 9607-9619 (1998)). For dominant selection of the Nav1.7-expressing clones, the expression plasmid co-expressed the neomycin resistance gene. The cell line was constructed in the human embryonic kidney cell line, HEK293, under the influence of the CMV major late promoter, and stable clones were selected using limiting dilution cloning and antibiotic selection using the neomycin analogue, G418. Recombinant beta and gamma subunits were not introduced into this cell line. Additional cell lines expressing recombinant Nav1.7 cloned from other species can also be used, alone or in combination with various beta subunits, gamma subunits or chaperones.Non-Recombinant Cell Lines Expressing Native Nav1.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 375.35, ALogP 4.59, HBA 4, HBD 2, PSA 62.58, QED 0.68
Compound (SMILES): OC[C@H](O)c1cccc(-c2ccc(Oc3ccc(C(F)(F)F)cc3)cc2)n1
InChIKey: SEEQNYSKARYQHN-IBGZPJMESA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FLIPR Assay: Recombinant Nav1.7 Cell Line: In vitro assays were performed in a recombinant cell line expressing cDNA encoding the alpha subunit (Nav1.7, SCN9a, PN1, NE) of human Nav1.7 (Accession No. NM__002977). The cell line was provided by investigators at Yale University (Cummins et al, J. Neurosci. 18(23): 9607-9619 (1998)). For dominant selection of the Nav1.7-expressing clones, the expression plasmid co-expressed the neomycin resistance gene. The cell line was constructed in the human embryonic kidney cell line, HEK293, under the influence of the CMV major late promoter, and stable clones were selected using limiting dilution cloning and antibiotic selection using the neomycin analogue, G418. Recombinant beta and gamma subunits were not introduced into this cell line. Additional cell lines expressing recombinant Nav1.7 cloned from other species can also be used, alone or in combination with various beta subunits, gamma subunits or chaperones.Non-Recombinant Cell Lines Expressing Native Nav1.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 375.35, ALogP 4.59, HBA 4, HBD 2, PSA 62.58, QED 0.68
Compound (SMILES): N#Cc1ccc(Oc2ccc(-c3cccc([C@H](O)CO)n3)cc2)cc1
InChIKey: VDMYHNAZWWEPTP-HXUWFJFHSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: FLIPR Assay: Recombinant Nav1.7 Cell Line: In vitro assays were performed in a recombinant cell line expressing cDNA encoding the alpha subunit (Nav1.7, SCN9a, PN1, NE) of human Nav1.7 (Accession No. NM__002977). The cell line was provided by investigators at Yale University (Cummins et al, J. Neurosci. 18(23): 9607-9619 (1998)). For dominant selection of the Nav1.7-expressing clones, the expression plasmid co-expressed the neomycin resistance gene. The cell line was constructed in the human embryonic kidney cell line, HEK293, under the influence of the CMV major late promoter, and stable clones were selected using limiting dilution cloning and antibiotic selection using the neomycin analogue, G418. Recombinant beta and gamma subunits were not introduced into this cell line. Additional cell lines expressing recombinant Nav1.7 cloned from other species can also be used, alone or in combination with various beta subunits, gamma subunits or chaperones.Non-Recombinant Cell Lines Expressing Native Nav1.
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 332.36, ALogP 3.44, HBA 5, HBD 2, PSA 86.37, QED 0.75