lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1Cc2cc(-c3cccnn3)ccc2C(c2cc3ccccc3o2)C1
InChIKey: UBPCUEVRWJIHLS-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 41.3 nM (pChEMBL 7.380000114440918)
Descriptors: MW 341.41, ALogP 4.47, HBA 4, HBD 0, PSA 42.16, QED 0.54
Compound (SMILES): CCN1Cc2ccccc2C(c2ccc3cn[nH]c3c2)C1
InChIKey: ZUZFJRJMEROGCY-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 277.37, ALogP 3.53, HBA 2, HBD 1, PSA 31.92, QED 0.78
Compound (SMILES): CN1Cc2ccccc2C(c2ccc3sncc3c2)C1
InChIKey: NUMHOXGZNHJTHF-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 280.4, ALogP 3.87, HBA 3, HBD 0, PSA 16.13, QED 0.67
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3)c(C(N)=O)nc2CC)c1
InChIKey: LVQGVZUDZSVRBM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 501.59, ALogP 3.55, HBA 8, HBD 3, PSA 125.71, QED 0.38
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCN(C)CC3)cc2)nc1Oc1cccc(NC(=O)/C=C/CN(C)C)c1
InChIKey: HIBWFBVIUFIIAN-JXMROGBWSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 558.69, ALogP 3.48, HBA 9, HBD 3, PSA 128.95, QED 0.3
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3)c(C(N)=O)nc2CC)c1C
InChIKey: AEBNZKWTLCUZBW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 515.62, ALogP 3.86, HBA 8, HBD 3, PSA 125.71, QED 0.37
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3)c(C(N)=O)nc2C(C)C)c1
InChIKey: NXOMUJIORBFHSR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 515.62, ALogP 4.11, HBA 8, HBD 3, PSA 125.71, QED 0.36
Compound (SMILES): C=CC(=O)N1CCC(c2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)c(C)c3)c(C(N)=O)nc2CC)CC1
InChIKey: OVIJPRKXAGWPIR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 574.77, ALogP 3.3, HBA 8, HBD 2, PSA 110.93, QED 0.46
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2cnc(C(N)=O)c(Nc3ccc(N4CCN(C)CC4)cc3)n2)c1
InChIKey: YGIBTSMHVRPSJH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 0.92 nM (pChEMBL 9.039999961853027)
Descriptors: MW 473.54, ALogP 2.99, HBA 8, HBD 3, PSA 125.71, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(OC)c(N4CCN(C)CC4)c3)c(C(N)=O)nc2CC)c1
InChIKey: DLYLXKIKTZVXLV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 531.62, ALogP 3.56, HBA 9, HBD 3, PSA 134.94, QED 0.34
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(CC)CC4)cc3)c(C(N)=O)nc2CC)c1
InChIKey: BLVSTWDZDHSEQQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 515.62, ALogP 3.94, HBA 8, HBD 3, PSA 125.71, QED 0.35
Compound (SMILES): C=CC(=O)N1CC[C@@H](Oc2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)cc3)c(C(N)=O)nc2CC)C1
InChIKey: QKDCLUARMDUUKN-XMMPIXPASA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 562.72, ALogP 2.26, HBA 9, HBD 2, PSA 120.16, QED 0.44
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3cnn(C4CCN(C)CC4)c3)c(C(N)=O)nc2C(C)C)c1
InChIKey: GWYBVGHLDQLEPN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 504.6, ALogP 3.82, HBA 9, HBD 3, PSA 140.29, QED 0.37
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)[C@@H](C)C4)cc3)c(C(N)=O)nc2CC)c1
InChIKey: VIKYVWOFKQNEHB-SFHVURJKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 515.62, ALogP 3.94, HBA 8, HBD 3, PSA 125.71, QED 0.37
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)[C@H](C)C4)cc3)c(C(N)=O)nc2CC)c1
InChIKey: VIKYVWOFKQNEHB-GOSISDBHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 515.62, ALogP 3.94, HBA 8, HBD 3, PSA 125.71, QED 0.37
Compound (SMILES): C=CC(=O)N1CCC(c2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)cc3)c(C(N)=O)nc2CC)CC1
InChIKey: ZBFUCVHDBVLZOQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 560.75, ALogP 2.99, HBA 8, HBD 2, PSA 110.93, QED 0.47
Compound (SMILES): CCC(=O)N1CC[C@@H](Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3)c(C(N)=O)nc2CC)C1
InChIKey: NHPBMYSFPQSLCG-LJQANCHMSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The phosphorylation activity on the peptide substrate of EGFR was investigated using LabChip (trademark) Systems (Caliper Life Sciences, Inc.). For the enzyme, EGFR [T790M/L858R] (Carna Biosciences, Inc.) was used. The test compound was added to a reaction liquid containing the enzyme protein to give 8 stages of final concentrations ranging from 300 nM to 0.1 nM, followed by incubation for 2 hours. Then, the substrate and the ATP solution were added thereto, followed by reaction for 1 hour. An ATP concentration of 1000 uM was used. A reaction liquid containing the enzyme protein but no test compound (in which the DMSO alone was added as a solvent at 0.4% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition.
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 481.6, ALogP 2.02, HBA 8, HBD 2, PSA 116.92, QED 0.59
Compound (SMILES): Oc1ccc(-c2nsc(-c3ccc(O)c(O)c3)n2)cc1O
InChIKey: MKKIWISQFSVGQX-UHFFFAOYSA-N
Target: Alpha-synuclein (SINGLE PROTEIN), Homo sapiens
UniProt: P37840
Assay: Competitive Binding Assay: The compounds prepared in the preceding examples were found to bind with high affinity to α-synuclein aggregates/fibrils that are found in the hallmark Lewy Bodies of Parkinson's disease. In order to assess relative binding affinities of the test compounds for aggregated α-synuclein, competition assays were set up with a radiolabeled molecule already known to bind to α-synuclein fibrils and non-radiolabeled test compounds. In order to induce its aggregation, α-synuclein was incubated in phosphate buffered saline (PBS, pH 7.4) at 37° C. for three days with shaking (1,400 rpm). Competitive binding assays were carried out in 12×75 mm borosilicate glass tubes. The reaction mixture contained 100 μL of α-synuclein aggregates (0.5-1 μg), [3H] positive reference compound #1 (100-200 nM diluted in PBS) and 50 μL of competing compounds (10−5-10−9 M, diluted serially in PBS containing 0.1% bovine serum albumin) in a final volume of 0.25 ml.
Measurement: Ki = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 302.31, ALogP 2.69, HBA 7, HBD 4, PSA 106.7, QED 0.54
Compound (SMILES): Oc1ccc(-c2ccc(-c3cc(O)c(O)c(O)c3)s2)cc1O
InChIKey: MFNMURUUYQGPJF-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 10080 nM (pChEMBL 5)
Descriptors: MW 316.33, ALogP 3.61, HBA 6, HBD 5, PSA 101.15, QED 0.46
Compound (SMILES): O=C(Nc1cc(O)c(O)cc1Br)c1ccc(O)c(O)c1
InChIKey: CSTGCMOOYZBMLI-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 32830 nM (pChEMBL 4.480000019073486)
Descriptors: MW 340.13, ALogP 2.52, HBA 5, HBD 5, PSA 110.02, QED 0.43
Compound (SMILES): Oc1ccc(-c2nc3cc(O)c(O)cc3o2)cc1O
InChIKey: QQMDEZWOGBKTGN-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 7340 nM (pChEMBL 5.130000114440918)
Descriptors: MW 259.22, ALogP 2.32, HBA 6, HBD 4, PSA 106.95, QED 0.5
Compound (SMILES): Oc1ccc(-c2cc(-c3ccc(O)c(O)c3)c(-c3ccc(O)c(O)c3)s2)cc1O
InChIKey: FXKBZSGWQMZEJJ-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 12540 nM (pChEMBL 4.900000095367432)
Descriptors: MW 408.43, ALogP 4.98, HBA 7, HBD 6, PSA 121.38, QED 0.27
Compound (SMILES): Oc1ccc(-c2cn(-c3ccc(O)c(O)c3)nn2)cc1O
InChIKey: LHRPIPGZXXRADL-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 33960 nM (pChEMBL 4.46999979019165)
Descriptors: MW 285.26, ALogP 1.76, HBA 7, HBD 4, PSA 111.63, QED 0.53
Compound (SMILES): O=C(/C=C/c1cc(O)c(O)cc1Br)c1ccc(O)c(O)c1
InChIKey: LLLJKOIYSCTHDB-HNQUOIGGSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 9020 nM (pChEMBL 5.039999961853027)
Descriptors: MW 351.15, ALogP 3.17, HBA 5, HBD 4, PSA 97.99, QED 0.39
Compound (SMILES): O=C(/C=C/c1ccc(O)c(O)c1)c1cc(O)c(O)cc1Br
InChIKey: NWXOWSOFKLEYFC-HNQUOIGGSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 21210 nM (pChEMBL 4.670000076293945)
Descriptors: MW 351.15, ALogP 3.17, HBA 5, HBD 4, PSA 97.99, QED 0.39
Compound (SMILES): CCCC(O)C(NCC(O)C(Cc1ccccc1)NC(=O)c1cccc(C(=O)N(C)C(C)c2ccccc2)c1)C(=O)NCC(C)C
InChIKey: PHXSVGGLTIKXSW-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition Assay: Previously, one of the following compounds discussed below have been studied in memapsin 2 inhibition (Ghosh et al., 2008), which the others are previously unpublished. Given the closely related substrate specificity for memapsin 1 and memapsin 2, the inventors chose to screen these previously identified memapsin 2 inhibitors for lead compounds as memapsin 1 inhibitors. Recombinant memapsin 1 ectodomain was prepared as described by Turner et al. (2002) and assayed using a commercially purchased fluorescent substrate.
Measurement: Ki = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 630.83, ALogP 4.11, HBA 6, HBD 5, PSA 131, QED 0.15
Compound (SMILES): CCCC(O)C(NCC(O)C(Cc1ccccc1)NC(=O)c1cc(C)cc(C(=O)N2CCCC2OC)c1)C(=O)NCC(C)C
InChIKey: WFZPJFBWUKKUTA-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: Previously, one of the following compounds discussed below have been studied in memapsin 2 inhibition (Ghosh et al., 2008), which the others are previously unpublished. Given the closely related substrate specificity for memapsin 1 and memapsin 2, the inventors chose to screen these previously identified memapsin 2 inhibitors for lead compounds as memapsin 1 inhibitors. Recombinant memapsin 1 ectodomain was prepared as described by Turner et al. (2002) and assayed using a commercially purchased fluorescent substrate.
Measurement: Ki = 6.56 nM (pChEMBL 8.180000305175781)
Descriptors: MW 610.8, ALogP 2.8, HBA 7, HBD 5, PSA 140.23, QED 0.2
Compound (SMILES): Nc1ccc(F)cc1NC(=O)c1cnc2c(C3CC3)c(N3CCNCC3)ccc2c1
InChIKey: FLZWFZZIIMRHAG-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 405.48, ALogP 3.5, HBA 5, HBD 3, PSA 83.28, QED 0.58
Compound (SMILES): Nc1ccccc1NC(=O)c1cnc2c(C3CC3)c(N3CCNCC3)ccc2c1
InChIKey: XIBXJQDDCQGVQI-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 387.49, ALogP 3.36, HBA 5, HBD 3, PSA 83.28, QED 0.6
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1ccc2c(c1)CC(=O)N2
InChIKey: VHEIIOIRXREBNO-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 285.28, ALogP 2.15, HBA 3, HBD 3, PSA 84.22, QED 0.74
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1ccc2[nH]cnc2c1
InChIKey: GJAPTZFOJVXYGW-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 270.27, ALogP 2.54, HBA 3, HBD 3, PSA 83.8, QED 0.63
Compound (SMILES): CN1CCN(c2ccc3cc(C(=O)Nc4ccc(F)cc4N)cnc3c2C2CC2)CC1
InChIKey: LVCPHIZMVPNXMG-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 419.5, ALogP 3.84, HBA 5, HBD 2, PSA 74.49, QED 0.63
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1cnc2c(ccn2CCN2CCOCC2)c1
InChIKey: YCCFSYIBQFCOEV-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 1532 nM (pChEMBL 5.820000171661377)
Descriptors: MW 383.43, ALogP 2.34, HBA 6, HBD 2, PSA 85.41, QED 0.66
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1ccc2c(cnn2CCN2CCOCC2)c1
InChIKey: FGMSMFBBLUIZAA-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 383.43, ALogP 2.34, HBA 6, HBD 2, PSA 85.41, QED 0.66
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1cnc2c(C3CC3)c(N3CCNCC3)ccc2c1
InChIKey: OSBRXOYKZATGBT-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 589 nM (pChEMBL 6.230000019073486)
Descriptors: MW 405.48, ALogP 3.5, HBA 5, HBD 3, PSA 83.28, QED 0.58
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1cnc2cc(N3CCNCC3)ccc2c1
InChIKey: LYMVFDJKXRRGGF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 365.41, ALogP 2.62, HBA 5, HBD 3, PSA 83.28, QED 0.62
Compound (SMILES): Nc1ccccc1NC(=O)c1cc2ccc(N3CCNCC3)cc2cn1
InChIKey: QBVCDTAHPQAPDK-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 299 nM (pChEMBL 6.519999980926514)
Descriptors: MW 347.42, ALogP 2.48, HBA 5, HBD 3, PSA 83.28, QED 0.63
Compound (SMILES): Nc1ccccc1NC(=O)c1cc2ccc(N3CCNCC3)c(C3CC3)c2cn1
InChIKey: PGPBWWAWYKVTCS-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 387.49, ALogP 3.36, HBA 5, HBD 3, PSA 83.28, QED 0.6
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1cc2ccc(N3CCNCC3)c(C3CC3)c2cn1
InChIKey: UEJXWSCTOFLCPH-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: Compounds for testing were diluted in DMSO to 50 fold the final concentration and a ten point three fold dilution series was made. The compounds were diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, 201.1M tris(2-carboxyethyl)phosphine) to 6 fold their final concentration. The HDAC enzymes (purchased from BPS Biosciences) were diluted to 1.5 fold their final concentration in assay buffer and pre-incubated with the compounds for 24 hours prior to addition of the substrate.The substrate tripeptide substrate 3 (synthesized in house) for each enzyme was equal to the Km as determined by a substrate titration curve. The enzyme and substrate concentrations used are given in Table 2. The substrates were diluted in assay buffer at 6x their final concentration with 0.3 uM sequencing grade trypsin (Sigma). The substrate/trypsin mix was added to the enzyme/compound mix, the plate was shaken for 60 seconds and placed into a Spectramax M5 microtiter plate.
Measurement: IC50 = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 405.48, ALogP 3.5, HBA 5, HBD 3, PSA 83.28, QED 0.58