lovingscience/chembl-v37-raw-activities huggingface dataset:
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 = 1.4 nM (pChEMBL 8.850000381469727)
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 = 1.2 nM (pChEMBL 8.920000076293945)
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 = 1.5 nM (pChEMBL 8.819999694824219)
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 = 1.1 nM (pChEMBL 8.960000038146973)
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 = 1.1 nM (pChEMBL 8.960000038146973)
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 = 1.2 nM (pChEMBL 8.920000076293945)
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 = 1.4 nM (pChEMBL 8.850000381469727)
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 = 1.7 nM (pChEMBL 8.770000457763672)
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 = 1.3 nM (pChEMBL 8.890000343322754)
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 = 1.8 nM (pChEMBL 8.739999771118164)
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 = 1.7 nM (pChEMBL 8.770000457763672)
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 = 1.3 nM (pChEMBL 8.890000343322754)
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 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 481.6, ALogP 2.02, HBA 8, HBD 2, PSA 116.92, QED 0.59
Compound (SMILES): C=CC(=O)N1CCC[C@@H](Oc2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)cc3)c(C(N)=O)nc2CC)C1
InChIKey: JSVPZRBHIKMSLF-RUZDIDTESA-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 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 576.75, ALogP 2.65, HBA 9, HBD 2, PSA 120.16, QED 0.43
Compound (SMILES): C=CC(=O)N1CCC[C@@H](Oc2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)c(C)c3)c(C(N)=O)nc2CC)C1
InChIKey: IQUSBNFTZLAHTF-RUZDIDTESA-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 590.77, ALogP 2.96, HBA 9, HBD 2, PSA 120.16, QED 0.42
Compound (SMILES): C=CC(=O)Nc1ccc(F)c(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3)c(C(N)=O)nc2CC)c1
InChIKey: GNMULHTXVBBKDA-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 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 519.58, ALogP 3.69, HBA 8, HBD 3, PSA 125.71, QED 0.37
Compound (SMILES): Oc1ccc(-c2cc(Br)c(-c3ccc(O)c(O)c3)s2)cc1O
InChIKey: VJLUXPGLXLBYEF-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 = 697 nM (pChEMBL 6.159999847412109)
Descriptors: MW 379.23, ALogP 4.67, HBA 5, HBD 4, PSA 80.92, QED 0.49
Compound (SMILES): Oc1ccc(-c2ncc(-c3cc(O)c(O)cc3Br)s2)cc1O
InChIKey: BNXKETCPNUQAFN-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 = 224 nM (pChEMBL 6.650000095367432)
Descriptors: MW 380.22, ALogP 4.06, HBA 6, HBD 4, PSA 93.81, QED 0.5
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 = 124 nM (pChEMBL 6.909999847412109)
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: 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 = 283 nM (pChEMBL 6.550000190734863)
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: 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 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 340.13, ALogP 2.52, HBA 5, HBD 5, PSA 110.02, QED 0.43
Compound (SMILES): O=C(Nc1ccc(O)c(O)c1)c1cc(O)c(O)cc1Br
InChIKey: INCSNXYPCWROCE-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 = 813 nM (pChEMBL 6.090000152587891)
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: 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 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 259.22, ALogP 2.32, HBA 6, HBD 4, PSA 106.95, QED 0.5
Compound (SMILES): Oc1ccc(-c2nnc(-c3cc(O)c(O)cc3O)o2)cc1O
InChIKey: YHDLVAJQSBQWJE-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 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 302.24, ALogP 1.93, HBA 8, HBD 5, PSA 140.07, QED 0.36
Compound (SMILES): Oc1ccc(-c2ccc(-c3ccc(O)c(O)c3)s2)cc1O
InChIKey: NXMDFVUDNRPFIE-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 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 300.34, ALogP 3.9, HBA 5, HBD 4, PSA 80.92, QED 0.54
Compound (SMILES): Oc1ccc(-c2cc(-c3ccc(O)c(O)c3)c(-c3ccc(O)c(O)c3)s2)cc1O
InChIKey: FXKBZSGWQMZEJJ-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 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 408.43, ALogP 4.98, HBA 7, HBD 6, PSA 121.38, QED 0.27
Compound (SMILES): Oc1ccc(-c2ccc(Br)s2)cc1O
InChIKey: FXWVJCUSEROQIC-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 = 506 nM (pChEMBL 6.300000190734863)
Descriptors: MW 271.13, ALogP 3.59, HBA 3, HBD 2, PSA 40.46, QED 0.78
Compound (SMILES): Oc1ccc(-c2nnc(-c3cc(O)c(O)cc3Br)s2)cc1O
InChIKey: SPTMWXCCWRKNJJ-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 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 381.21, ALogP 3.46, HBA 7, HBD 4, PSA 106.7, QED 0.51
Compound (SMILES): Oc1ccc(-c2nnc(-c3ccc(O)c(O)c3)o2)cc1O
InChIKey: WCJKCKPWAQAOTM-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 = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 286.24, ALogP 2.23, HBA 7, HBD 4, PSA 119.84, QED 0.53
Compound (SMILES): Oc1ccc(-c2cn(-c3ccc(O)c(O)c3)nn2)cc1O
InChIKey: LHRPIPGZXXRADL-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 = 697 nM (pChEMBL 6.159999847412109)
Descriptors: MW 285.26, ALogP 1.76, HBA 7, HBD 4, PSA 111.63, QED 0.53
Compound (SMILES): Oc1ccc(-c2ncc(Br)s2)cc1O
InChIKey: NUCPGNOGGCIGAO-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 = 765 nM (pChEMBL 6.119999885559082)
Descriptors: MW 272.12, ALogP 2.98, HBA 4, HBD 2, PSA 53.35, QED 0.78
Compound (SMILES): Oc1ccc(-c2cnc(-c3ccc(O)c(O)c3)o2)cc1O
InChIKey: NMCHVKJWRNDKNB-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 = 659 nM (pChEMBL 6.179999828338623)
Descriptors: MW 285.25, ALogP 2.83, HBA 6, HBD 4, PSA 106.95, QED 0.54
Compound (SMILES): Oc1ccc(-c2nnc(-c3ccc(O)c(O)c3)s2)cc1O
InChIKey: SQQUCACGXUDDAS-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 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 302.31, ALogP 2.69, HBA 7, HBD 4, PSA 106.7, QED 0.54
Compound (SMILES): COc1cc(-c2nnc(-c3cc(O)c(O)cc3I)s2)ccc1O
InChIKey: JADNEWLFQQSJPE-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 = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 442.23, ALogP 3.6, HBA 7, HBD 3, PSA 95.7, QED 0.42
Compound (SMILES): Oc1ccc(-c2ccc(-c3cc(O)c(O)c(I)c3)s2)cc1O
InChIKey: RGFVDLSNFNHUBU-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 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 426.23, ALogP 4.51, HBA 5, HBD 4, PSA 80.92, QED 0.36
Compound (SMILES): Oc1ccc(-c2cnc(-c3cc(O)c(O)cc3Br)s2)cc1O
InChIKey: JPXUJSPDZHMJPH-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 = 177 nM (pChEMBL 6.75)
Descriptors: MW 380.22, ALogP 4.06, HBA 6, HBD 4, PSA 93.81, QED 0.5
Compound (SMILES): CC(=O)Oc1ccc(-c2nnc(-c3cc(OC(C)=O)c(OC(C)=O)cc3I)s2)cc1OC(C)=O
InChIKey: HSQFQHMAYHYAJX-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 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 596.36, ALogP 4.18, HBA 11, HBD 0, PSA 130.98, QED 0.23
Compound (SMILES): Oc1ccc(-c2cnc(-c3cc(O)c(O)cc3Br)o2)cc1O
InChIKey: RBVMVUMZAZTJJP-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 = 639 nM (pChEMBL 6.190000057220459)
Descriptors: MW 364.15, ALogP 3.59, HBA 6, HBD 4, PSA 106.95, QED 0.52
Compound (SMILES): O=[N+]([O-])c1cc(O)c(O)cc1Cc1cc(O)c(O)cc1[N+](=O)[O-]
InChIKey: ITCDMONXMIEPSH-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 = 970 nM (pChEMBL 6.010000228881836)
Descriptors: MW 322.23, ALogP 1.92, HBA 8, HBD 4, PSA 167.2, QED 0.38
Compound (SMILES): N#Cc1cc(O)c(O)cc1Cc1ccc(O)c(O)c1
InChIKey: GKZBOXAFRCUNCY-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 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 257.25, ALogP 1.97, HBA 5, HBD 4, PSA 104.71, QED 0.62