lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)CCNc1ccc(Nc2nccc(-c3ccc(N4CCC(C(N)=O)CC4)c(C#N)c3)n2)cn1
InChIKey: XQDYTMWSHHRIQF-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 485.6, ALogP 2.83, HBA 9, HBD 3, PSA 136.09, QED 0.42
Compound (SMILES): CN(C)CCNc1ccc(Nc2nccc(-c3ccc(N4CCC(O)CC4)c(C#N)c3)n2)cn1
InChIKey: YCJNUXDJGVNYGW-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 458.57, ALogP 3.09, HBA 9, HBD 3, PSA 113.23, QED 0.47
Compound (SMILES): CC(=O)Nc1ccc(Nc2nccc(-c3ccc(N4CC(O)C4)c(C#N)c3)n2)cn1
InChIKey: ULOABNKVPRZZBK-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 401.43, ALogP 2.29, HBA 8, HBD 3, PSA 127.06, QED 0.59
Compound (SMILES): CNC(=O)[C@H]1CCCN1c1ccc(-c2ccnc(Nc3ccc(NC(C)=O)nc3)n2)cc1C#N
InChIKey: JYXIRRRXLOQEPK-OAQYLSRUSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 9000 nM (pChEMBL 5.046000003814697)
Descriptors: MW 456.51, ALogP 2.83, HBA 8, HBD 3, PSA 135.93, QED 0.52
Compound (SMILES): CNC(=O)C1CCN(c2ccc(-c3ccnc(Nc4ccc(NC(C)=O)nc4)n3)cc2C#N)CC1
InChIKey: RZYARNXACVQGAH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 470.54, ALogP 3.07, HBA 8, HBD 3, PSA 135.93, QED 0.5
Compound (SMILES): CN(C)CCNc1ccc(Nc2nccc(-c3ccc(N4CC[C@H](F)C4)c(C#N)c3)n2)cn1
InChIKey: NGQHJZXAWIBXQH-IBGZPJMESA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 446.53, ALogP 3.68, HBA 8, HBD 2, PSA 93, QED 0.54
Compound (SMILES): CC(=O)Nc1ccc(Nc2nccc(-c3ccc(N4CCC[C@H]4C(N)=O)c(C#N)c3)n2)cn1
InChIKey: UVDGBQZYCWLDNX-FQEVSTJZSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 442.48, ALogP 2.57, HBA 8, HBD 3, PSA 149.92, QED 0.53
Compound (SMILES): COC[C@H]1CCCN1c1ccc(-c2ccnc(Nc3ccc(NC(C)=O)nc3)n2)cc1C#N
InChIKey: NWLDIIJVPIJBAB-HXUWFJFHSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 443.51, ALogP 3.73, HBA 8, HBD 2, PSA 116.06, QED 0.57
Compound (SMILES): CN(C)CCNc1ccc(Nc2nccc(-c3ccc(N4CCC[C@@H]4C(N)=O)c(C#N)c3)n2)cn1
InChIKey: QOTZPVWTNYTSNI-JOCHJYFZSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 471.57, ALogP 2.58, HBA 9, HBD 3, PSA 136.09, QED 0.43
Compound (SMILES): CC(=O)Nc1ccc(Nc2nccc(-c3ccc(N4CC[C@@H](O)C4)c(C#N)c3)n2)cn1
InChIKey: HNZHNMAWIKSPKY-GOSISDBHSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 415.46, ALogP 2.68, HBA 8, HBD 3, PSA 127.06, QED 0.58
Compound (SMILES): Cn1cc(Nc2nccc(-c3ccc(N4CC[C@H](O)C4)c(C#N)c3)n2)cn1
InChIKey: FTRUCIDFCFXYAU-INIZCTEOSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 361.41, ALogP 2.06, HBA 8, HBD 2, PSA 102.89, QED 0.73
Compound (SMILES): Cn1cc(Nc2nccc(-c3ccc(N4CCC(C(N)=O)CC4)c(C#N)c3)n2)cn1
InChIKey: DQGNBSROXUZAHD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 402.46, ALogP 2.19, HBA 8, HBD 2, PSA 125.75, QED 0.67
Compound (SMILES): CO[C@H]1CCN(c2ccc(-c3ccnc(Nc4ccc(NC(C)=O)nc4)n3)cc2C#N)C1
InChIKey: WGXGLZXOMKXVEB-IBGZPJMESA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 429.48, ALogP 3.34, HBA 8, HBD 2, PSA 116.06, QED 0.61
Compound (SMILES): CN1CCC(Nc2ccc(Nc3nccc(-c4ccc(N5CC[C@@H](F)C5)c(C#N)c4)n3)cn2)CC1
InChIKey: AYVFJLIIZPMLDY-HXUWFJFHSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 472.57, ALogP 4.21, HBA 8, HBD 2, PSA 93, QED 0.55
Compound (SMILES): CN1CCC(Nc2ccc(Nc3nccc(-c4ccc(N5CC[C@H](F)C5)c(C#N)c4)n3)cn2)CC1
InChIKey: AYVFJLIIZPMLDY-FQEVSTJZSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 472.57, ALogP 4.21, HBA 8, HBD 2, PSA 93, QED 0.55
Compound (SMILES): CN1CCC(Nc2ccc(Nc3nccc(-c4ccc(N5CC[C@H](O)C5)c(C#N)c4)n3)cn2)CC1
InChIKey: WXMBBWGYXZCGHO-QFIPXVFZSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 470.58, ALogP 3.23, HBA 9, HBD 3, PSA 113.23, QED 0.5
Compound (SMILES): CN1CCC(Nc2ccc(Nc3nccc(-c4ccc(N5CCC(F)(F)C5)c(C#N)c4)n3)cn2)CC1
InChIKey: LZDUEEDZQIKXFJ-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Inhibitions studies were performed using a time-resolved fluorescence-based Lanthascreen assay. Phosphorylation of a fluorescein-labelled substrate peptide is measured using terbium-labeled phosphospecific antibodies. Terbium is excited at 340 nm and the FRET energy transfer to fluorescein is measured at 495 and 520 nm. The emission ratio between 520 and 495 is a measure of the level of phosphorylation of the substrate by the kinase.Kinase inhibition assays (10 Î¼L) were performed at 20Â° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 Î¼M) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBÎ± substrate (DRHDSGLDSMKDE), 20 Î¼M ATP, 2 nM or 8 nM IKKÎµ or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 490.56, ALogP 4.51, HBA 8, HBD 2, PSA 93, QED 0.52
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3ccccc3F)ccc1OC1(CCC1)C21COC1
InChIKey: PQPCAOQHCPZEDG-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 3590 nM (pChEMBL 5.449999809265137)
Descriptors: MW 380.42, ALogP 3.36, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cccc(F)c3)ccc1OC1(CCC1)C21COC1
InChIKey: AORINRZTSWKVOX-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 2310 nM (pChEMBL 5.639999866485596)
Descriptors: MW 380.42, ALogP 3.36, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): COc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: ICTGQWRYTVZEMV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 696 nM (pChEMBL 6.159999847412109)
Descriptors: MW 392.46, ALogP 3.23, HBA 6, HBD 1, PSA 75.3, QED 0.85
Compound (SMILES): Cc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: JSKKJULDTHCLMY-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 2270 nM (pChEMBL 5.639999866485596)
Descriptors: MW 376.46, ALogP 3.53, HBA 5, HBD 1, PSA 66.07, QED 0.83
Compound (SMILES): N#Cc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: OSDCIYPOSBDCJI-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 1680 nM (pChEMBL 5.78000020980835)
Descriptors: MW 387.44, ALogP 3.1, HBA 6, HBD 1, PSA 89.86, QED 0.81
Compound (SMILES): CCOc1cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)cc(C(F)(F)F)c1
InChIKey: NPVLNYWBAKGQLZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 2210 nM (pChEMBL 5.659999847412109)
Descriptors: MW 474.48, ALogP 4.64, HBA 6, HBD 1, PSA 75.3, QED 0.7
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cc(F)ccc3F)ccc1OC1(CCC1)C21COC1
InChIKey: FJXRFMBYVGLNFX-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 1870 nM (pChEMBL 5.730000019073486)
Descriptors: MW 398.41, ALogP 3.5, HBA 5, HBD 1, PSA 66.07, QED 0.8
Compound (SMILES): CCOc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: SRCMYQVGJCIJMT-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 2020 nM (pChEMBL 5.699999809265137)
Descriptors: MW 406.48, ALogP 3.62, HBA 6, HBD 1, PSA 75.3, QED 0.84
Compound (SMILES): N#C/C=C/c1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: HZHQWAJHXXVIFY-GORDUTHDSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 2450 nM (pChEMBL 5.610000133514404)
Descriptors: MW 413.48, ALogP 3.76, HBA 6, HBD 1, PSA 89.86, QED 0.76
Compound (SMILES): CCOc1cc(F)cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: UJFGYZLSPBPCBC-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 1670 nM (pChEMBL 5.78000020980835)
Descriptors: MW 424.47, ALogP 3.76, HBA 6, HBD 1, PSA 75.3, QED 0.81
Compound (SMILES): N#Cc1cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)ccc1F
InChIKey: MBTSGUSQJYKBNL-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 3630 nM (pChEMBL 5.440000057220459)
Descriptors: MW 405.43, ALogP 3.24, HBA 6, HBD 1, PSA 89.86, QED 0.79
Compound (SMILES): NC1=NC2(CO1)c1cc(C3=CCCCC3)ccc1OC1(CCC1)C21COC1
InChIKey: GTVHCOSZWNNPFK-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 3270 nM (pChEMBL 5.489999771118164)
Descriptors: MW 366.46, ALogP 3.52, HBA 5, HBD 1, PSA 66.07, QED 0.83
Compound (SMILES): COc1ccc(F)c(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: DCFHBMJLBSTLIB-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 635 nM (pChEMBL 6.199999809265137)
Descriptors: MW 410.45, ALogP 3.37, HBA 6, HBD 1, PSA 75.3, QED 0.82
Compound (SMILES): COc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1F
InChIKey: YWEZIZZHYAWWDG-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 773 nM (pChEMBL 6.110000133514404)
Descriptors: MW 410.45, ALogP 3.37, HBA 6, HBD 1, PSA 75.3, QED 0.82
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cccc(F)c3F)ccc1OC1(CCC1)C21COC1
InChIKey: QSPCHUPRAPAASU-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 1670 nM (pChEMBL 5.78000020980835)
Descriptors: MW 398.41, ALogP 3.5, HBA 5, HBD 1, PSA 66.07, QED 0.8
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc(Cl)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: ZEAMOJNDSBWBMU-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: Ki = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 384.86, ALogP 3.73, HBA 5, HBD 1, PSA 66.07, QED 0.81
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc(C4CC4)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: UKEAETWEXZCSQW-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 389 nM (pChEMBL 6.409999847412109)
Descriptors: MW 390.48, ALogP 3.96, HBA 5, HBD 1, PSA 66.07, QED 0.84
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc(C(F)(F)F)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: LRUHIAIIFSMMGU-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 903 nM (pChEMBL 6.039999961853027)
Descriptors: MW 418.42, ALogP 4.1, HBA 5, HBD 1, PSA 66.07, QED 0.76
Compound (SMILES): COc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: NTYCQRSCQKAIKY-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 401 nM (pChEMBL 6.400000095367432)
Descriptors: MW 380.44, ALogP 3.09, HBA 6, HBD 1, PSA 75.3, QED 0.87