lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1c(F)cc(NC(=O)c2ccc(Cl)cn2)cc1[C@@]1(CF)N=C(N)O[C@@H]2C[C@@H]21
InChIKey: NOYKSAYHCYSSCZ-CQOVVYFZSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 422.82, ALogP 3.03, HBA 6, HBD 2, PSA 98.83, QED 0.77
Compound (SMILES): COc1c(F)cc(NC(=O)c2ccc(Cl)cn2)cc1[C@]1(CF)N=C(N)O[C@H]2C[C@H]21
InChIKey: NOYKSAYHCYSSCZ-VZMUKZCBSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 422.82, ALogP 3.03, HBA 6, HBD 2, PSA 98.83, QED 0.77
Compound (SMILES): CC(C)Oc1cnc(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: MCEGGIMKRBWGNC-PGICJIBASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 731.5 nM (pChEMBL 6.139999866485596)
Descriptors: MW 435.41, ALogP 2.85, HBA 7, HBD 2, PSA 111.72, QED 0.72
Compound (SMILES): C#C[C@@H](C)Oc1cnc(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: JHAMOFBHPBZXSW-ZDDLIGRPSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 445.4, ALogP 2.46, HBA 7, HBD 2, PSA 111.72, QED 0.66
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3csc(C(F)F)n3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: QDHSVFNSCJPDEW-UISHXFLQSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 194.5 nM (pChEMBL 6.710000038146973)
Descriptors: MW 432.37, ALogP 3.67, HBA 6, HBD 2, PSA 89.6, QED 0.71
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3coc(C(F)F)n3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: HWYPKJUOACSAKT-UISHXFLQSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 32.2 nM (pChEMBL 7.489999771118164)
Descriptors: MW 416.31, ALogP 3.2, HBA 6, HBD 2, PSA 102.74, QED 0.73
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3coc(C#CC4CC4)n3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: KGUJRISOHXKAPX-CQURBHOASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 24805 nM (pChEMBL 4.610000133514404)
Descriptors: MW 430.39, ALogP 3.02, HBA 6, HBD 2, PSA 102.74, QED 0.73
Compound (SMILES): COc1cnc(C(=O)Nc2cc(F)c(Cl)c([C@]3(CF)N=C(N)O[C@H]4C[C@H]43)c2)cn1
InChIKey: MURDSGANCUOHQI-AKCUIXRJSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 127.5 nM (pChEMBL 6.889999866485596)
Descriptors: MW 423.81, ALogP 2.43, HBA 7, HBD 2, PSA 111.72, QED 0.76
Compound (SMILES): Cc1cc(OC(F)F)cnc1C(=O)Nc1cc(F)c(Cl)c([C@]2(CF)N=C(N)O[C@H]3C[C@H]32)c1
InChIKey: LPZILOJMOGQQQE-STYXZAMGSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 472.83, ALogP 3.93, HBA 6, HBD 2, PSA 98.83, QED 0.62
Compound (SMILES): Cn1nc(C(F)F)cc1C(=O)Nc1ccc(F)c([C@@]2(C(F)F)N=C(N)O[C@@H]3C[C@@H]32)c1
InChIKey: NVQXJLSXTPSNHQ-FWWORTMDSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 429.35, ALogP 2.94, HBA 6, HBD 2, PSA 94.53, QED 0.72
Compound (SMILES): COc1cnc(C(=O)Nc2cc(F)c(Cl)c([C@@]3(CF)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: MURDSGANCUOHQI-ZWRLQWNWSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 423.81, ALogP 2.43, HBA 7, HBD 2, PSA 111.72, QED 0.76
Compound (SMILES): Cc1cc(OC(F)F)cnc1C(=O)Nc1cc(F)c(Cl)c([C@@]2(CF)N=C(N)O[C@@H]3C[C@@H]32)c1
InChIKey: LPZILOJMOGQQQE-CJAGKMTESA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 40.3 nM (pChEMBL 7.389999866485596)
Descriptors: MW 472.83, ALogP 3.93, HBA 6, HBD 2, PSA 98.83, QED 0.62
Compound (SMILES): Cc1nc(OCC(F)(F)F)cnc1C(=O)Nc1cc(F)c(Cl)c([C@]2(CF)N=C(N)O[C@H]3C[C@H]32)c1
InChIKey: UZKQOQQRJKLGGG-KPGGICDASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 225.5 nM (pChEMBL 6.650000095367432)
Descriptors: MW 505.83, ALogP 3.67, HBA 7, HBD 2, PSA 111.72, QED 0.58
Compound (SMILES): CC(C)n1cc(Cl)c(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)n1
InChIKey: QCBSNZWYUBQTMD-GEDNVKPRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 441.84, ALogP 3.7, HBA 6, HBD 2, PSA 94.53, QED 0.74
Compound (SMILES): C#C[C@H](C)Oc1cnc(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: JHAMOFBHPBZXSW-YUURZZLOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 445.4, ALogP 2.46, HBA 7, HBD 2, PSA 111.72, QED 0.66
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3nn(C(F)F)cc3Cl)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: LZAUUZOANIOYOF-UISHXFLQSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 13.7 nM (pChEMBL 7.860000133514404)
Descriptors: MW 449.77, ALogP 3.52, HBA 6, HBD 2, PSA 94.53, QED 0.68
Compound (SMILES): NC1=N[C@](CF)(c2cc(NC(=O)c3nn(C(F)F)cc3Cl)ccc2F)[C@H]2C[C@H]2O1
InChIKey: UNQHKFVRHXLGIN-DKRRZFASSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 23.2 nM (pChEMBL 7.630000114440918)
Descriptors: MW 431.78, ALogP 3.22, HBA 6, HBD 2, PSA 94.53, QED 0.71
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3cnc(OCc4nccs4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: PBOFUWPMJICINF-QURLWZIUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 19.2 nM (pChEMBL 7.71999979019165)
Descriptors: MW 490.47, ALogP 3.1, HBA 9, HBD 2, PSA 124.61, QED 0.52
Compound (SMILES): Cc1nc(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)co1
InChIKey: UENZQKOWSUZQRC-MNRXQERYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 61.3 nM (pChEMBL 7.210000038146973)
Descriptors: MW 380.33, ALogP 2.57, HBA 6, HBD 2, PSA 102.74, QED 0.85
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3cnc(OCc4ncco4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: MNJPSURDWKMEDQ-QURLWZIUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 12.4 nM (pChEMBL 7.909999847412109)
Descriptors: MW 474.4, ALogP 2.63, HBA 9, HBD 2, PSA 137.75, QED 0.53
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3coc(CF)n3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: ZMWQZZXSNRHAOY-DKRRZFASSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 398.32, ALogP 2.73, HBA 6, HBD 2, PSA 102.74, QED 0.75
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3cnc(OCc4cscn4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: DSGZYYDLHMDDDV-CQURBHOASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 36.6 nM (pChEMBL 7.440000057220459)
Descriptors: MW 490.47, ALogP 3.1, HBA 9, HBD 2, PSA 124.61, QED 0.52
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3cnc(OCc4cncs4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: JLJYQQNXSQRJBC-CQURBHOASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 86.7 nM (pChEMBL 7.059999942779541)
Descriptors: MW 490.47, ALogP 3.1, HBA 9, HBD 2, PSA 124.61, QED 0.52
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3cnc(OCc4cnco4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: VITNRXGBCGCIJP-CQURBHOASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 81.1 nM (pChEMBL 7.090000152587891)
Descriptors: MW 474.4, ALogP 2.63, HBA 9, HBD 2, PSA 137.75, QED 0.53
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3ccc(OCc4nccs4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: FCDRQLUQQGNTSM-WTBBCNCBSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 82.4 nM (pChEMBL 7.079999923706055)
Descriptors: MW 489.48, ALogP 3.7, HBA 8, HBD 2, PSA 111.72, QED 0.52
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3ccc(OCc4ncco4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: MVZJHTYGEYEXBX-WTBBCNCBSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 36.6 nM (pChEMBL 7.440000057220459)
Descriptors: MW 473.41, ALogP 3.23, HBA 8, HBD 2, PSA 124.86, QED 0.54
Compound (SMILES): NC1=N[C@@](c2cc(NC(=O)c3cnc(OCc4cocn4)cn3)ccc2F)(C(F)F)[C@H]2C[C@H]2O1
InChIKey: CSQREPJIQPTOLQ-CQURBHOASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 23.3 nM (pChEMBL 7.630000114440918)
Descriptors: MW 474.4, ALogP 2.63, HBA 9, HBD 2, PSA 137.75, QED 0.53
Compound (SMILES): C[C@H](F)c1nc(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)co1
InChIKey: UTYIZWMPBOJMLJ-DGOADCAFSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 2880 nM (pChEMBL 5.539999961853027)
Descriptors: MW 412.34, ALogP 3.29, HBA 6, HBD 2, PSA 102.74, QED 0.73
Compound (SMILES): Cc1csc(C(=O)Nc2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)c1
InChIKey: DPZOJXONVHUCFJ-WHWRDJHUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 = 190.5 nM (pChEMBL 6.71999979019165)
Descriptors: MW 395.41, ALogP 3.64, HBA 5, HBD 2, PSA 76.71, QED 0.83
Compound (SMILES): O[C@H](CNCC(Cc1ccccn1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1)C(F)(F)F
InChIKey: KWSWXVITIKXBHI-OAQYLSRUSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 568.44, ALogP 5.92, HBA 5, HBD 2, PSA 63.61, QED 0.3
Compound (SMILES): O[C@@H](CN(C[C@H](O)C(F)(F)F)CC(Cc1ccccc1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1)C(F)(F)F
InChIKey: BLYMRZJGKWXSTD-ZEQRLZLVSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 2811 nM (pChEMBL 5.550000190734863)
Descriptors: MW 679.5, ALogP 7.16, HBA 5, HBD 2, PSA 62.16, QED 0.2
Compound (SMILES): O[C@H](CNCC(Cc1ccccc1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1)C(F)(F)F
InChIKey: DEYLVZYDQPRONF-JOCHJYFZSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 567.45, ALogP 6.53, HBA 4, HBD 2, PSA 50.72, QED 0.27
Compound (SMILES): Cc1ccc(CC(CNC[C@@H](O)C(F)(F)F)(c2cccc(OC(F)(F)F)c2)c2cccc(OC(F)(F)F)c2)cc1
InChIKey: POXQHEFGTYZPRE-HSZRJFAPSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 581.48, ALogP 6.83, HBA 4, HBD 2, PSA 50.72, QED 0.26
Compound (SMILES): FC(F)(F)CCNCC(Cc1ccccc1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1
InChIKey: MMIXYPKSFYLMML-UHFFFAOYSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 551.45, ALogP 7.55, HBA 3, HBD 1, PSA 30.49, QED 0.21
Compound (SMILES): Oc1c(F)cccc1CNCC(Cc1ccccc1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1
InChIKey: XKTUHCZBSMFKJE-UHFFFAOYSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 579.51, ALogP 7.65, HBA 4, HBD 2, PSA 50.72, QED 0.19
Compound (SMILES): FC(F)(F)Oc1cccc(C(CNc2ncc(N3CCOCC3)cn2)(Cc2ccccc2)c2cccc(OC(F)(F)F)c2)c1
InChIKey: NBXOQHWYURABLM-UHFFFAOYSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 247.6 nM (pChEMBL 6.610000133514404)
Descriptors: MW 618.58, ALogP 6.75, HBA 7, HBD 1, PSA 68.74, QED 0.2
Compound (SMILES): O=S(=O)(CC(F)(F)F)NCC(Cc1ccccc1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1
InChIKey: HIGZSPIFWKSORN-UHFFFAOYSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 601.49, ALogP 6.49, HBA 4, HBD 1, PSA 64.63, QED 0.27
Compound (SMILES): CC(C)OC(=O)CCNCC(Cc1ccccc1)(c1cccc(OC(F)(F)F)c1)c1cccc(OC(F)(F)F)c1
InChIKey: GSNFIMJMAFEKLP-UHFFFAOYSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay: Compounds of the present invention inhibit CETP-dependent cholesterol ester transfer from HDL to LDL as described here. Dilutions of compounds in DMSO (1 μl) are added to BD plates (#353232). To this is added 20 μl of a mixture containing 3H-CE/HDL (0.15 μl), biotinylated LDL (5 μg protein/ml final concentration) and unlabeled HDL (16 μg/ml final concentration) in a buffer containing 50 mM HEPES, pH 7.4, 150 mM NaCl and 0.05% sodium azide. Reactions are initiated by the addition of 10 μl of buffer containing purified human recombinant CETP, and incubated at 37 C. At the end of the reaction, 60 μl of LEADseeker beads (#RPNQ0261, 2 mg/ml in buffer containing 1 mg/ml BSA and 0.05 mg protein/ml HDL) are added, the plates are covered and subsequently read. Background activity is determined in a set of wells that receive buffer but no CETP.
Measurement: IC50 = 1089 nM (pChEMBL 5.960000038146973)
Descriptors: MW 569.54, ALogP 6.94, HBA 5, HBD 1, PSA 56.79, QED 0.15
Compound (SMILES): O=S(=O)(Cl)CCCCCCCc1cccc(OCc2ccccc2)c1
InChIKey: KIACCMMCOMJSCP-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Enzyme Assay: All compound solutions are made to a concentration of 10 mM in DMSO. To test the stability of the compounds in enzyme assay conditions, 25 nmoles of the compound are incubated in TME buffer with 0.1% BSA (final volume of 250 uL) for 15 minutes at 37 C. Samples (100 uL) are taken at the start of the assay and after 15 minutes, diluted 1:5 with acetonitrile and centrifuged (20,000 RCF, five minutes, room temperature) to precipitate the proteins. The resulting supernatant is injected onto the HPLC. Calculations for determining the percent compound remaining are described in the following equation:% R=Peak Area (T15)/Peak Area (T0)To determine whether or not the compounds are good substrates for FAAH, 25 nmoles of the compound were incubated with 75 ug enzyme preparation in TME buffer with 0.1% BSA (final volume 250 uL). The reaction mixture is treated in the same manner as described above.
Measurement: Ki = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 380.94, ALogP 5.33, HBA 3, HBD 0, PSA 43.37, QED 0.39
Compound (SMILES): O=S(=O)(Cl)CCCCCCCc1ccccc1OCc1ccccc1
InChIKey: VFNANICQTWXKCU-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Enzyme Assay: All compound solutions are made to a concentration of 10 mM in DMSO. To test the stability of the compounds in enzyme assay conditions, 25 nmoles of the compound are incubated in TME buffer with 0.1% BSA (final volume of 250 uL) for 15 minutes at 37 C. Samples (100 uL) are taken at the start of the assay and after 15 minutes, diluted 1:5 with acetonitrile and centrifuged (20,000 RCF, five minutes, room temperature) to precipitate the proteins. The resulting supernatant is injected onto the HPLC. Calculations for determining the percent compound remaining are described in the following equation:% R=Peak Area (T15)/Peak Area (T0)To determine whether or not the compounds are good substrates for FAAH, 25 nmoles of the compound were incubated with 75 ug enzyme preparation in TME buffer with 0.1% BSA (final volume 250 uL). The reaction mixture is treated in the same manner as described above.
Measurement: Ki = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 380.94, ALogP 5.33, HBA 3, HBD 0, PSA 43.37, QED 0.39