lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1cc(F)c(-c2ccncc2F)nc1C(=O)Nc1cnccc1[C@@H]1CCC[C@H](N)C1
InChIKey: NIGKYNBXMPAUEZ-OLZOCXBDSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 424.46, ALogP 3.64, HBA 6, HBD 3, PSA 119.81, QED 0.59
Compound (SMILES): CC1CC(c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)=CC(O)C1
InChIKey: MFQHDSGLLLJSPV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 439.44, ALogP 4.99, HBA 4, HBD 2, PSA 75.11, QED 0.6
Compound (SMILES): C[C@@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](O)[C@H]1O
InChIKey: AISMIGRIJQYZHW-OQHSJCBVSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 457.45, ALogP 4.05, HBA 5, HBD 3, PSA 95.34, QED 0.55
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1F
InChIKey: SKYIOLUXCWYHKN-AMWSZZEWSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 458.46, ALogP 4.99, HBA 4, HBD 2, PSA 80.9, QED 0.54
Compound (SMILES): COC1C(N)CCN(c2c(NC(=O)c3nc(-c4c(F)cccc4F)sc3N)cnn2C)CC12CC2
InChIKey: PXHLQMRYWVBLIJ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Pim Kinase Binding Activity: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.016 nM (pChEMBL 10.800000190734863)
Descriptors: MW 503.58, ALogP 2.99, HBA 9, HBD 3, PSA 124.32, QED 0.49
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CCCC(F)(CN)CC1
InChIKey: FZOYIDXYLVSURK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Pim Kinase Binding Activity: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.068 nM (pChEMBL 10.170000076293945)
Descriptors: MW 479.53, ALogP 3.31, HBA 8, HBD 3, PSA 115.09, QED 0.52
Compound (SMILES): COC1(CN)CCCN(c2c(NC(=O)c3nc(-c4c(F)cccc4F)sc3N)cnn2C)CC1
InChIKey: WUTWUAHPGGGZHA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Pim Kinase Binding Activity: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.103 nM (pChEMBL 9.989999771118164)
Descriptors: MW 491.57, ALogP 2.99, HBA 9, HBD 3, PSA 124.32, QED 0.48
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CC[C@](C)(N)CC(F)(F)C1
InChIKey: YLJCMWKIAARCQT-FQEVSTJZSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Pim Kinase Binding Activity: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.026 nM (pChEMBL 10.59000015258789)
Descriptors: MW 497.52, ALogP 3.61, HBA 8, HBD 3, PSA 115.09, QED 0.47
Compound (SMILES): Cc1cccnc1NC[C@H]1CC[C@H](NC(=O)c2cc(C(F)(F)F)ccc2Cl)CC1
InChIKey: UVHYWEIDDCPJSI-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 425.88, ALogP 5.46, HBA 3, HBD 2, PSA 54.02, QED 0.67
Compound (SMILES): Cc1ncccc1NC[C@H]1CC[C@H](NC(=O)c2cc(C(F)(F)F)ccc2Cl)CC1
InChIKey: WQQLZZFCXBPXGZ-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 425.88, ALogP 5.46, HBA 3, HBD 2, PSA 54.02, QED 0.67
Compound (SMILES): Cc1nc(NC[C@H]2CC[C@H](NC(=O)c3cc(Cl)cnc3Cl)CC2)sc1C
InChIKey: ZVNVSBYNJGKUBN-MQMHXKEQSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 413.37, ALogP 4.86, HBA 5, HBD 2, PSA 66.91, QED 0.69
Compound (SMILES): O=C(O)c1ccc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)nc1
InChIKey: NVNFYSIRDPSNEG-NNUKFRKNSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 6425 nM (pChEMBL 5.190000057220459)
Descriptors: MW 455.86, ALogP 4.85, HBA 4, HBD 3, PSA 91.32, QED 0.58
Compound (SMILES): CN(C)Cc1ccc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)nc1
InChIKey: RWPZVPQWHITMOL-RZDIXWSQSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 1241 nM (pChEMBL 5.909999847412109)
Descriptors: MW 468.95, ALogP 5.22, HBA 4, HBD 2, PSA 57.26, QED 0.58
Compound (SMILES): C[C@@H]1C[C@@H](NC(=O)c2cc(C(F)(F)F)ccc2Cl)CC[C@@H]1CNc1cc(-c2ccc(F)cc2)[nH]n1
InChIKey: RYGKCEUKVORYIA-OGWOLHLISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 508.95, ALogP 6.53, HBA 3, HBD 3, PSA 69.81, QED 0.33
Compound (SMILES): Cc1cnc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)s1
InChIKey: LRQOAOQISQHLMX-MQMHXKEQSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 431.91, ALogP 5.52, HBA 4, HBD 2, PSA 54.02, QED 0.65
Compound (SMILES): Cc1cc(C)nc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)c1
InChIKey: VFIJKRAYAOLSRK-JCNLHEQBSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 439.91, ALogP 5.77, HBA 3, HBD 2, PSA 54.02, QED 0.62
Compound (SMILES): Cc1ccc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)nc1
InChIKey: DPVLQYBEEUQDRO-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 425.88, ALogP 5.46, HBA 3, HBD 2, PSA 54.02, QED 0.67
Compound (SMILES): Cc1cccc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)n1
InChIKey: MCMLZOUDURNIIV-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 425.88, ALogP 5.46, HBA 3, HBD 2, PSA 54.02, QED 0.67
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2ccccc2Cl)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: YEDWIMCNMTWBHK-CTYIDZIISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 445.31, ALogP 6.41, HBA 2, HBD 2, PSA 41.13, QED 0.56
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNCc2cc(-c3ccccc3)on2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: RHHARZHZRKTXNS-RUCARUNLSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 491.94, ALogP 6.09, HBA 4, HBD 2, PSA 67.16, QED 0.42
Compound (SMILES): Cc1nc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)sc1C
InChIKey: FBDAJXKOBAVFEV-CTYIDZIISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 445.94, ALogP 5.83, HBA 4, HBD 2, PSA 54.02, QED 0.61
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2cc(-c3ccc(F)cc3)n[nH]2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: QFDRLKJTTYNBOX-PPUGGXLSSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 494.92, ALogP 6.29, HBA 3, HBD 3, PSA 69.81, QED 0.35
Compound (SMILES): CCCc1cc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)n[nH]1
InChIKey: JMKWIZNFXVNIDO-CTYIDZIISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 442.91, ALogP 5.44, HBA 3, HBD 3, PSA 69.81, QED 0.53
Compound (SMILES): CC(C)c1cc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)n[nH]1
InChIKey: DEEJQEXSVPUIPE-CTYIDZIISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 442.91, ALogP 5.61, HBA 3, HBD 3, PSA 69.81, QED 0.54
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2cccnc2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: TXMARZZBGFWVMT-CTYIDZIISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 411.86, ALogP 5.15, HBA 3, HBD 2, PSA 54.02, QED 0.71
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2ccccc2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: LYGMVXMHRDGOJK-CZIWCDLHSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 410.87, ALogP 5.76, HBA 2, HBD 2, PSA 41.13, QED 0.66
Compound (SMILES): Cc1ncc(Cl)cc1C(=O)N[C@H]1CC[C@H](CNc2nc(C)c(C)s2)CC1
InChIKey: MPZRUZLCKNUHAY-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 392.96, ALogP 4.52, HBA 5, HBD 2, PSA 66.91, QED 0.78
Compound (SMILES): O=C(N[C@H]1CC[C@H](Cn2ccc(N3CCNC3=O)n2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: YPJPOBMCXNYBOD-CTYIDZIISA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 469.9, ALogP 4.07, HBA 4, HBD 2, PSA 79.26, QED 0.69
Compound (SMILES): Cc1cc(C)n(C[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)n1
InChIKey: HSTHFIYASRGMSO-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 413.87, ALogP 5.16, HBA 3, HBD 1, PSA 46.92, QED 0.75
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2cc(C3CC3)n[nH]2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: DGGIRPOXDCLAAO-NNUKFRKNSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 440.9, ALogP 5.36, HBA 3, HBD 3, PSA 69.81, QED 0.57
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2cccc(F)c2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: GDIJRJMHPKMCNM-SAZUREKKSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 428.86, ALogP 5.9, HBA 2, HBD 2, PSA 41.13, QED 0.58
Compound (SMILES): Cc1cncc(NC[C@H]2CC[C@H](NC(=O)c3cc(C(F)(F)F)ccc3Cl)CC2)c1
InChIKey: BHPGCOVJDHVVNO-KOMQPUFPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 425.88, ALogP 5.46, HBA 3, HBD 2, PSA 54.02, QED 0.67
Compound (SMILES): CN(Cc1cc(-c2ccccc2)n[nH]1)C[C@H]1CC[C@H](NC(=O)c2cc(Cl)ccc2Cl)CC1
InChIKey: YPRYLHXVAFRJQF-IRJFHVNHSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 471.43, ALogP 5.8, HBA 3, HBD 2, PSA 61.02, QED 0.46
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2ccccc2)CC1)c1cccc(Cl)c1
InChIKey: BMHDAOMNPMWTER-RHDGDCLCSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 342.87, ALogP 4.74, HBA 2, HBD 2, PSA 41.13, QED 0.82
Compound (SMILES): O=C(N[C@H]1CC[C@H](CNc2cccc3ncccc23)CC1)c1cccc(C(F)(F)F)c1
InChIKey: GISASCVJDUCZHI-RUCARUNLSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 427.47, ALogP 5.65, HBA 3, HBD 2, PSA 54.02, QED 0.55
Compound (SMILES): O=C(N[C@H]1CC[C@@H](CNc2cc(-c3ccc(F)cc3)n[nH]2)CC1)c1cc(C(F)(F)F)ccc1Cl
InChIKey: QFDRLKJTTYNBOX-UJKQEGAGSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 3225 nM (pChEMBL 5.489999771118164)
Descriptors: MW 494.92, ALogP 6.29, HBA 3, HBD 3, PSA 69.81, QED 0.35
Compound (SMILES): Cc1ccncc1NC[C@H]1CC[C@@H](NC(=O)c2cc(C(F)(F)F)ccc2Cl)CC1
InChIKey: QDGKJWRDSBAYEX-FZNQNYSPSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 2205 nM (pChEMBL 5.659999847412109)
Descriptors: MW 425.88, ALogP 5.46, HBA 3, HBD 2, PSA 54.02, QED 0.67
Compound (SMILES): CC(Nc1ccccc1)[C@H]1CC[C@H](NC(=O)c2cc(C(F)(F)F)ccc2Cl)CC1
InChIKey: XKXGPCJOUDRYIM-UOUXQUKFSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: In Vitro Inhibition Assay: Chinese hamster ovary (CHO) cells expressing either the human recombinant CRF-1 or CRF-2a receptors (Chen et al., Proc Natl Acad Sci USA 90, 8967-8971, 1993; Liaw et al., Endocrinology 137, 72-77, 1996) are propagated in Dulbecco's modified Eagle medium supplemented with 10% foetal calf serum, non-essential amino acids, 100 U/ml penicillin, 100 mg/l streptomycin and 1 g/l geneticin (G418). For cyclic AMP determinations the Homogeneous Time-Resolved Fluoresce (HTRF) cAMP dynamic 2 kit (Cisbio International, France) was used as per manufacturers' instructions. CHO cells, previously cryopreserved, were thawed, centrifuged for 7 mins at 1200 rpm and resuspended in serum free media, then pipetted out onto clear bottomed black tissue culture treated 384-well microtitre plates (Corning Inc, US) at 2,000 cells per well. Compounds of the invention, prepared in DMSO, and subsequently diluted 50 fold in assay buffer (1x Hanks balanced salt solution, 0.2% (w/v) bovine serum albumin.
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 424.89, ALogP 6.15, HBA 2, HBD 2, PSA 41.13, QED 0.6