lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1CN=C(n2cnc(Cl)c2)C=C2c3cccc(-c4cncc(F)c4)c3CCN12
InChIKey: VTWLXSUHZLOQIX-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 407.84, ALogP 3.42, HBA 5, HBD 0, PSA 63.38, QED 0.62
Compound (SMILES): COCCc1cn(C2=NCC(=O)N3CCc4c(cccc4-c4ccc(F)nc4)C3=C2)cn1
InChIKey: PFKGLLNLLQFKKB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 431.47, ALogP 2.96, HBA 6, HBD 0, PSA 72.61, QED 0.6
Compound (SMILES): C=Cc1cccc2c1CCN1C(=O)CN=C(n3cnc(COC)c3)C=C21
InChIKey: FCTBXASGWAKIAB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 348.41, ALogP 2.36, HBA 5, HBD 0, PSA 59.72, QED 0.86
Compound (SMILES): CCc1cn(C2=NCC(=O)N3CCc4c(cccc4-c4ccc(F)cc4)C3=C2)cn1
InChIKey: FGROCZOSPDQYJD-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 400.46, ALogP 3.94, HBA 4, HBD 0, PSA 50.49, QED 0.65
Compound (SMILES): Cc1cnc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)o1
InChIKey: RCNPMPFRYJOVFT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 399.45, ALogP 3.41, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)n2)C=C2c3cccc(-c4nccnc4F)c3CCN12
InChIKey: BQZQFDZRXQZAGE-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 415.43, ALogP 2.44, HBA 7, HBD 0, PSA 89.16, QED 0.64
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)n2)C=C2c3cccc(-c4ncccc4F)c3CCN12
InChIKey: HLUILDPLTLOJIW-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.44, ALogP 3.04, HBA 6, HBD 0, PSA 76.27, QED 0.65
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4cncs4)c3CCN12
InChIKey: JEVQKQPQVOOHMD-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 401.5, ALogP 3.57, HBA 6, HBD 0, PSA 63.38, QED 0.66
Compound (SMILES): Cc1ncc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)s1
InChIKey: ZZHJIIGEEWQXPG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 3881 nM (pChEMBL 5.409999847412109)
Descriptors: MW 415.52, ALogP 3.88, HBA 6, HBD 0, PSA 63.38, QED 0.64
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4cnccn4)c3CCN12
InChIKey: LZZDJGGNZRMJTC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 1953 nM (pChEMBL 5.710000038146973)
Descriptors: MW 396.45, ALogP 2.9, HBA 6, HBD 0, PSA 76.27, QED 0.67
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)n2)C=C2c3cccc(-c4nccs4)c3CCN12
InChIKey: DOLMPPAKPUQJRP-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 761 nM (pChEMBL 6.119999885559082)
Descriptors: MW 402.48, ALogP 2.97, HBA 7, HBD 0, PSA 76.27, QED 0.66
Compound (SMILES): COCCc1cn(C2=NCC(=O)N3CCc4c(cccc4-c4nccs4)C3=C2)cn1
InChIKey: FCCXJYITQHDTHC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 1053 nM (pChEMBL 5.980000019073486)
Descriptors: MW 419.51, ALogP 2.88, HBA 7, HBD 0, PSA 72.61, QED 0.65
Compound (SMILES): CCOCc1cn(C2=NCC(=O)N3CCc4c(cccc4-c4nc(C)cs4)C3=C2)cn1
InChIKey: PNGHTMBIJIFCGV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 433.54, ALogP 3.54, HBA 7, HBD 0, PSA 72.61, QED 0.63
Compound (SMILES): CCOCc1cn(C2=NCC(=O)N3CCc4c(cccc4-c4nccs4)C3=C2)cn1
InChIKey: RFNYROKTILDQQA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 1857 nM (pChEMBL 5.730000019073486)
Descriptors: MW 419.51, ALogP 3.23, HBA 7, HBD 0, PSA 72.61, QED 0.65
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4cnccc4F)c3CCN12
InChIKey: YKCQLQAONFBECQ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 5860 nM (pChEMBL 5.230000019073486)
Descriptors: MW 413.46, ALogP 3.65, HBA 5, HBD 0, PSA 63.38, QED 0.64
Compound (SMILES): CCc1cccc2c1CCN1C(=O)CN=C(n3cnc(C(C)C)c3)C=C21
InChIKey: ZDULCLFYDBDVDF-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 348.45, ALogP 3.25, HBA 4, HBD 0, PSA 50.49, QED 0.84
Compound (SMILES): CCCc1cccc2c1CCN1C(=O)CNC(n3cnc(C)c3)C=C21
InChIKey: ZREKQGANSVVZCG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 336.44, ALogP 2.67, HBA 4, HBD 1, PSA 50.16, QED 0.94
Compound (SMILES): COCc1cn(C2=NCC(=O)N3CCc4c(cccc4C4CCC4)C3=C2)cn1
InChIKey: XMXWQEOSRWRHAD-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 376.46, ALogP 2.98, HBA 5, HBD 0, PSA 59.72, QED 0.83
Compound (SMILES): Cc1ncn(C2=NCC(=O)N3CCc4c(cccc4C4CCC4)C3=C2)n1
InChIKey: DDWMQMPXDUENHH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 636 nM (pChEMBL 6.199999809265137)
Descriptors: MW 347.42, ALogP 2.54, HBA 5, HBD 0, PSA 63.38, QED 0.8
Compound (SMILES): COCc1ncn(C2=NCC(=O)N3CCc4c(cccc4C4CC4)C3=C2)n1
InChIKey: DRSBFTQQPIMGRO-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 363.42, ALogP 1.99, HBA 6, HBD 0, PSA 72.61, QED 0.84
Compound (SMILES): CC(C)c1cn(C2=NCC(=O)N3CCc4c(-c5ccc(F)nc5)ccnc4C3=C2)cn1
InChIKey: PEPXYJIHFLPBBZ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 416.46, ALogP 3.29, HBA 6, HBD 0, PSA 76.27, QED 0.6
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4cccnc4F)c3CCN12
InChIKey: STQRBUUKFGQBAK-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 413.46, ALogP 3.65, HBA 5, HBD 0, PSA 63.38, QED 0.6
Compound (SMILES): O=C1CN=C(n2cnc(C3CCC3)c2)C=C2c3cccc(-c4cccnc4F)c3CCN12
InChIKey: IWSHCMVSVZSTRY-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 427.48, ALogP 4.04, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cc1cn(C2=NCC(=O)N3CCc4c(cccc4-c4cnc(C)o4)C3=C2)cn1
InChIKey: PPSDHKKDSGMSTM-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.42, ALogP 2.84, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): COc1ccc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)cn1
InChIKey: IOOFWYZPFLWWHC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 425.49, ALogP 3.52, HBA 6, HBD 0, PSA 72.61, QED 0.64
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4cc[nH]n4)c3CCN12
InChIKey: HCVGVQZSMDHHLL-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 8261 nM (pChEMBL 5.079999923706055)
Descriptors: MW 384.44, ALogP 2.84, HBA 5, HBD 1, PSA 79.17, QED 0.74
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4cnc(F)nc4)c3CCN12
InChIKey: LPSCBFOKMBVBFD-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 11993 nM (pChEMBL 4.920000076293945)
Descriptors: MW 414.44, ALogP 3.04, HBA 6, HBD 0, PSA 76.27, QED 0.6
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccnc(F)c4)c3CCN12
InChIKey: WVFRQPCEUDYPFL-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 18193 nM (pChEMBL 4.739999771118164)
Descriptors: MW 413.46, ALogP 3.65, HBA 5, HBD 0, PSA 63.38, QED 0.6
Compound (SMILES): COCc1cn(C2=NCC(=O)N3CCc4c(C5CC5)ccc(F)c4C3=C2)cn1
InChIKey: VTJXVUYJMWDVSF-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 687 nM (pChEMBL 6.159999847412109)
Descriptors: MW 380.42, ALogP 2.73, HBA 5, HBD 0, PSA 59.72, QED 0.82
Compound (SMILES): CO[C@H](C)c1cn(C2=NCC(=O)N3CCc4c(C5CC5)ccc(F)c4C3=C2)cn1
InChIKey: RDYYIBJARKPHCO-CYBMUJFWSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 3206 nM (pChEMBL 5.489999771118164)
Descriptors: MW 394.45, ALogP 3.29, HBA 5, HBD 0, PSA 59.72, QED 0.8
Compound (SMILES): COCc1cn(C2=NCC(=O)N3CCc4c(cc(F)cc4C4CC4)C3=C2)cn1
InChIKey: CQQUHBDYEUOOMX-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 380.42, ALogP 2.73, HBA 5, HBD 0, PSA 59.72, QED 0.82
Compound (SMILES): C[C@@H]1CN2c3c(cc4c(N5CCOC5=O)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
InChIKey: CDAHTPNJGHKIRM-CEFVDNRUSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0AES4
Assay: Fluorescence Polarisation Assay: In a black, 384-well polystyrene assay plate, 30 microliters/well of 5 nM Escherichia coli DNA gyrase A/B tetramer and 130 micrograms/mL of topological^ relaxed plasmid containing the triplex-forming sequence TTCTTCTTCTTCTTCTTCTTCTTCTTC (SEQ ID NO: 1) in an assay buffer consisting of 35 mM Tris-HCI (pH 7.5), 24 mM KCI, 4 mM MgCI2, 2 mM dithiothreitol, 1.8 mM spermidine, 5% (v/v) glycerol, 200 nM bovine serum albumin, 0.8%dimethylsulfoxide, and 0.3 mM ATP were incubated at ambient temperature for (typically 30 minutes) in the absence or presence of 5 -10 different concentrations of test compound. The supercoiling reactions were quenched by the addition of 10 microliters/well of 40 nM oligodeoxynucleotide probe in 3X triplex-forming buffer consisting of 150 mM NaCI, and 150 mM sodium acetate at pH 3.5. The oligodeoxynucleotide probe was 5'-BODIPY-FL-labeled TTCTTCTTC (SEQ ID NO:2). After 60 minutes, the fluorescence anisotropy of the BODIPY- FL was measured in a Tecan Ultra plate.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 473.42, ALogP 0.81, HBA 9, HBD 2, PSA 143.31, QED 0.58
Compound (SMILES): COC[C@H]1COC(=O)N1c1noc2c(F)c3c(cc12)CC1(C(=O)NC(=O)NC1=O)[C@H]1[C@H](C)O[C@H](C)CN31
InChIKey: WDIBDPAHQXIEKL-YFEKEUHLSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0AES4
Assay: Fluorescence Polarisation Assay: In a black, 384-well polystyrene assay plate, 30 microliters/well of 5 nM Escherichia coli DNA gyrase A/B tetramer and 130 micrograms/mL of topological^ relaxed plasmid containing the triplex-forming sequence TTCTTCTTCTTCTTCTTCTTCTTCTTC (SEQ ID NO: 1) in an assay buffer consisting of 35 mM Tris-HCI (pH 7.5), 24 mM KCI, 4 mM MgCI2, 2 mM dithiothreitol, 1.8 mM spermidine, 5% (v/v) glycerol, 200 nM bovine serum albumin, 0.8%dimethylsulfoxide, and 0.3 mM ATP were incubated at ambient temperature for (typically 30 minutes) in the absence or presence of 5 -10 different concentrations of test compound. The supercoiling reactions were quenched by the addition of 10 microliters/well of 40 nM oligodeoxynucleotide probe in 3X triplex-forming buffer consisting of 150 mM NaCI, and 150 mM sodium acetate at pH 3.5. The oligodeoxynucleotide probe was 5'-BODIPY-FL-labeled TTCTTCTTC (SEQ ID NO:2). After 60 minutes, the fluorescence anisotropy of the BODIPY- FL was measured in a Tecan Ultra plate.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 517.47, ALogP 0.83, HBA 10, HBD 2, PSA 152.54, QED 0.56
Compound (SMILES): C[C@@H]1CN2c3c(cc4c(N5C(=O)OC[C@@H]5c5ncccn5)noc4c3F)CC3(C(=O)NC(=O)NC3=O)C2[C@H](C)O1
InChIKey: XNHIBFIYRMMRCU-MNYFDSNTSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0AES4
Assay: Fluorescence Polarisation Assay: In a black, 384-well polystyrene assay plate, 30 microliters/well of 5 nM Escherichia coli DNA gyrase A/B tetramer and 130 micrograms/mL of topological^ relaxed plasmid containing the triplex-forming sequence TTCTTCTTCTTCTTCTTCTTCTTCTTC (SEQ ID NO: 1) in an assay buffer consisting of 35 mM Tris-HCI (pH 7.5), 24 mM KCI, 4 mM MgCI2, 2 mM dithiothreitol, 1.8 mM spermidine, 5% (v/v) glycerol, 200 nM bovine serum albumin, 0.8%dimethylsulfoxide, and 0.3 mM ATP were incubated at ambient temperature for (typically 30 minutes) in the absence or presence of 5 -10 different concentrations of test compound. The supercoiling reactions were quenched by the addition of 10 microliters/well of 40 nM oligodeoxynucleotide probe in 3X triplex-forming buffer consisting of 150 mM NaCI, and 150 mM sodium acetate at pH 3.5. The oligodeoxynucleotide probe was 5'-BODIPY-FL-labeled TTCTTCTTC (SEQ ID NO:2). After 60 minutes, the fluorescence anisotropy of the BODIPY- FL was measured in a Tecan Ultra plate.
Measurement: IC50 > 2100 nM (pChEMBL 5.677999973297119)
Descriptors: MW 551.49, ALogP 1.35, HBA 11, HBD 2, PSA 169.09, QED 0.44
Compound (SMILES): C[C@@H]1CN2c3c(cc4c(N5C(=O)OC[C@H]5c5ncccn5)noc4c3F)CC3(C(=O)NC(=O)NC3=O)C2[C@H](C)O1
InChIKey: XNHIBFIYRMMRCU-KISLSHQNSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0AES4
Assay: Fluorescence Polarisation Assay: In a black, 384-well polystyrene assay plate, 30 microliters/well of 5 nM Escherichia coli DNA gyrase A/B tetramer and 130 micrograms/mL of topological^ relaxed plasmid containing the triplex-forming sequence TTCTTCTTCTTCTTCTTCTTCTTCTTC (SEQ ID NO: 1) in an assay buffer consisting of 35 mM Tris-HCI (pH 7.5), 24 mM KCI, 4 mM MgCI2, 2 mM dithiothreitol, 1.8 mM spermidine, 5% (v/v) glycerol, 200 nM bovine serum albumin, 0.8%dimethylsulfoxide, and 0.3 mM ATP were incubated at ambient temperature for (typically 30 minutes) in the absence or presence of 5 -10 different concentrations of test compound. The supercoiling reactions were quenched by the addition of 10 microliters/well of 40 nM oligodeoxynucleotide probe in 3X triplex-forming buffer consisting of 150 mM NaCI, and 150 mM sodium acetate at pH 3.5. The oligodeoxynucleotide probe was 5'-BODIPY-FL-labeled TTCTTCTTC (SEQ ID NO:2). After 60 minutes, the fluorescence anisotropy of the BODIPY- FL was measured in a Tecan Ultra plate.
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 551.49, ALogP 1.35, HBA 11, HBD 2, PSA 169.09, QED 0.44
Compound (SMILES): COC(=O)c1c(-c2ccc(Br)cc2)csc1N
InChIKey: FTCYGPXJXBDSIU-UHFFFAOYSA-N
Target: Protein kinase C zeta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q05513
Assay: Kinase-Glo End-Point Assay: The IC50 values for PKCl-diMeO and compounds described herein and illustrated in FIG. 6 are described in Table 2. The IC50 values were determined using a Kinase-Glo end-point assay with 125 ng/ml aPKCζ, 25 μM CREBtide, and 0.1 μM ATP.
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 312.19, ALogP 3.55, HBA 4, HBD 1, PSA 52.32, QED 0.86
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): CS(=O)(=O)c1cc(-c2ccc(C[C@@H](C#N)NC(=O)C34CCC(CC3)CN4)c(F)c2)ccc1C#N
InChIKey: WTFPMTZBRYAXAT-MHVXWQKQSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhbition Assay: The recombinant human DPPI was diluted in TAGZyme buffer to 1 U/ml (38.1 ug/ml, respectively), and then activated by mixing in a 1:2 ratio with a Cysteamine aqueous solution (2 mM) and incubating for 5 min at room temperature.Five uL test compound (final concentration 0.1 nM to 100 uM) in aqua bidest (containing 4% DMSO, final DMSO concentration 1%) were mixed with 10 uL of DPPI in MES buffer (final concentration 0.0125 ng/uL) and incubated for 10 min. Then, 5 uL of substrate in MES buffer (final concentration 50 uM) were added. The microtiter plates were then incubated at room temperature for 30 min. Then, the reaction was stopped by adding 10 uL of Gly-Phe-DMK in MES-buffer (final concentration 1 uM). The fluorescence in the wells was determined using a Molecular Devices SpectraMax M5 Fluorescence Reader (Ex 360 nm, Em 460 nm) or an Envision Fluorescence Reader (Ex 355 nm, Em 460 nm).
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 480.57, ALogP 2.85, HBA 6, HBD 2, PSA 122.85, QED 0.66
Compound (SMILES): CN1C(=O)Cc2ccc(-c3ccc(C[C@@H](C#N)NC(=O)C45CCC(CC4)CN5)cc3)cc21
InChIKey: FLUKFHZYRHSYID-ZRTADFRUSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhbition Assay: The recombinant human DPPI was diluted in TAGZyme buffer to 1 U/ml (38.1 ug/ml, respectively), and then activated by mixing in a 1:2 ratio with a Cysteamine aqueous solution (2 mM) and incubating for 5 min at room temperature.Five uL test compound (final concentration 0.1 nM to 100 uM) in aqua bidest (containing 4% DMSO, final DMSO concentration 1%) were mixed with 10 uL of DPPI in MES buffer (final concentration 0.0125 ng/uL) and incubated for 10 min. Then, 5 uL of substrate in MES buffer (final concentration 50 uM) were added. The microtiter plates were then incubated at room temperature for 30 min. Then, the reaction was stopped by adding 10 uL of Gly-Phe-DMK in MES-buffer (final concentration 1 uM). The fluorescence in the wells was determined using a Molecular Devices SpectraMax M5 Fluorescence Reader (Ex 360 nm, Em 460 nm) or an Envision Fluorescence Reader (Ex 355 nm, Em 460 nm).
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 428.54, ALogP 2.96, HBA 4, HBD 2, PSA 85.23, QED 0.77
Compound (SMILES): CS(=O)(=O)c1cc(-c2ccc(C[C@@H](C#N)NC(=O)C34CCC(CC3)CN4)cc2)ccc1C#N
InChIKey: KMWDHMSUUMKGQS-JMNVSDKBSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhbition Assay: The recombinant human DPPI was diluted in TAGZyme buffer to 1 U/ml (38.1 ug/ml, respectively), and then activated by mixing in a 1:2 ratio with a Cysteamine aqueous solution (2 mM) and incubating for 5 min at room temperature.Five uL test compound (final concentration 0.1 nM to 100 uM) in aqua bidest (containing 4% DMSO, final DMSO concentration 1%) were mixed with 10 uL of DPPI in MES buffer (final concentration 0.0125 ng/uL) and incubated for 10 min. Then, 5 uL of substrate in MES buffer (final concentration 50 uM) were added. The microtiter plates were then incubated at room temperature for 30 min. Then, the reaction was stopped by adding 10 uL of Gly-Phe-DMK in MES-buffer (final concentration 1 uM). The fluorescence in the wells was determined using a Molecular Devices SpectraMax M5 Fluorescence Reader (Ex 360 nm, Em 460 nm) or an Envision Fluorescence Reader (Ex 355 nm, Em 460 nm).
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 462.58, ALogP 2.71, HBA 6, HBD 2, PSA 122.85, QED 0.68
Compound (SMILES): CN1Cc2cc(-c3ccc(C[C@@H](C#N)NC(=O)C45CCC(CC4)CN5)cc3)ccc2C1=O
InChIKey: NOSUEQLRRACAQS-ZRTADFRUSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhbition Assay: The recombinant human DPPI was diluted in TAGZyme buffer to 1 U/ml (38.1 ug/ml, respectively), and then activated by mixing in a 1:2 ratio with a Cysteamine aqueous solution (2 mM) and incubating for 5 min at room temperature.Five uL test compound (final concentration 0.1 nM to 100 uM) in aqua bidest (containing 4% DMSO, final DMSO concentration 1%) were mixed with 10 uL of DPPI in MES buffer (final concentration 0.0125 ng/uL) and incubated for 10 min. Then, 5 uL of substrate in MES buffer (final concentration 50 uM) were added. The microtiter plates were then incubated at room temperature for 30 min. Then, the reaction was stopped by adding 10 uL of Gly-Phe-DMK in MES-buffer (final concentration 1 uM). The fluorescence in the wells was determined using a Molecular Devices SpectraMax M5 Fluorescence Reader (Ex 360 nm, Em 460 nm) or an Envision Fluorescence Reader (Ex 355 nm, Em 460 nm).
Measurement: IC50 = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 428.54, ALogP 3.02, HBA 4, HBD 2, PSA 85.23, QED 0.77
Compound (SMILES): CS(=O)(=O)c1ccc(-c2ccc(C[C@@H](C#N)NC(=O)C34CCC(CC3)CN4)c(F)c2)cc1
InChIKey: YLYRPDLKZYLBQM-XUGLNINTSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhbition Assay: The recombinant human DPPI was diluted in TAGZyme buffer to 1 U/ml (38.1 ug/ml, respectively), and then activated by mixing in a 1:2 ratio with a Cysteamine aqueous solution (2 mM) and incubating for 5 min at room temperature.Five uL test compound (final concentration 0.1 nM to 100 uM) in aqua bidest (containing 4% DMSO, final DMSO concentration 1%) were mixed with 10 uL of DPPI in MES buffer (final concentration 0.0125 ng/uL) and incubated for 10 min. Then, 5 uL of substrate in MES buffer (final concentration 50 uM) were added. The microtiter plates were then incubated at room temperature for 30 min. Then, the reaction was stopped by adding 10 uL of Gly-Phe-DMK in MES-buffer (final concentration 1 uM). The fluorescence in the wells was determined using a Molecular Devices SpectraMax M5 Fluorescence Reader (Ex 360 nm, Em 460 nm) or an Envision Fluorescence Reader (Ex 355 nm, Em 460 nm).
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 455.56, ALogP 2.98, HBA 5, HBD 2, PSA 99.06, QED 0.7