lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(c1cccc(F)c1-n1nccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: VEJWAVKRPRJLDD-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 447.39, ALogP 3.5, HBA 6, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): Cc1cccc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c1-n1nccn1
InChIKey: VMCVDMDKIAUUAU-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 443.43, ALogP 3.67, HBA 6, HBD 0, PSA 73.14, QED 0.62
Compound (SMILES): O=C(c1c(F)cccc1-n1nccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: SGBSAQGVDFRKJX-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 447.39, ALogP 3.5, HBA 6, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): O=C(c1ccc(F)cc1-c1ncccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: AXZNZGVQOXKZLA-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 458.42, ALogP 4.38, HBA 5, HBD 0, PSA 68.21, QED 0.54
Compound (SMILES): O=C(c1ccccc1-n1cnnc1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: CTAUDMRXJCJSKS-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 429.4, ALogP 3.36, HBA 6, HBD 0, PSA 73.14, QED 0.64
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)n1
InChIKey: DIVFYQCMVDWPOD-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 444.42, ALogP 3.07, HBA 7, HBD 0, PSA 86.03, QED 0.61
Compound (SMILES): Cc1ccc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c(-n2nccn2)n1
InChIKey: FTIPLKXQDISZMV-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 444.42, ALogP 3.07, HBA 7, HBD 0, PSA 86.03, QED 0.61
Compound (SMILES): O=C(c1ncccc1-n1nccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: FLULXEHMBMNJCY-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 430.39, ALogP 2.76, HBA 7, HBD 0, PSA 86.03, QED 0.63
Compound (SMILES): COc1c(F)cccc1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: RYMOHHYAOSEKIU-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: Receptor Radioligand Binding Assay: Human Orexin 2 Receptor:HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 410.37, ALogP 3.93, HBA 4, HBD 0, PSA 51.66, QED 0.72
Compound (SMILES): Cc1cccc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c1-c1ncco1
InChIKey: IIVBMGSJEAWDEA-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Human Orexin 1 Receptor Ca2+ Mobilization Assay: CHO cells stably transfected with the human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12, 10% FBS, 1×pen-strep, 400 μg/ml G418. Cells were seeded on to 384-well Packard viewplates at a density of 10,000 cells/well and incubated overnight at 37° C., 5% CO2. The cells were dye-loaded with BD Calcium Assay kit (BD, cat #640178) in HBSS (Gibco, cat #14025-092) with 2.5 mM probenecid and incubated at 37° C., 5% CO2 for 45 min. Cells were pre-incubated with compounds (diluted in DMEM/F-12) for 15-30 minutes before agonist (orexin A, 10 nM) stimulation. Ligand-induced Ca2+ release was measured using a Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices, Sunnyvale, Calif.). Functional responses were measured as peak fluorescence intensity minus basal. The concentration of agonist that produced a half-maximal response is represented by the EC50 value. Antagonistic potency values were converted to apparent pKB values using a modified Cheng-Prusoff correction. Apparent pKB=−log IC50/1+[conc agonist/EC50].
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 443.43, ALogP 4.75, HBA 5, HBD 0, PSA 68.46, QED 0.58
Compound (SMILES): O=C(c1cccc(F)c1-n1ccnn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: RNUWTSJVSRFNSZ-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: Receptor Radioligand Binding Assay: Human Orexin 2 Receptor:HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 447.39, ALogP 3.5, HBA 6, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): Cc1ccc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c(-n2ccnn2)n1
InChIKey: ICOFMFLOEJHBPA-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 462 nM (pChEMBL 6.329999923706055)
Descriptors: MW 444.42, ALogP 3.07, HBA 7, HBD 0, PSA 86.03, QED 0.61
Compound (SMILES): CCOc1ccc(C)nc1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: HBQVLSLDECXOPX-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 421.42, ALogP 3.88, HBA 5, HBD 0, PSA 64.55, QED 0.73
Compound (SMILES): O=C(c1c(F)cccc1-c1ncccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: IGPUBGBQVDTOBH-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 633 nM (pChEMBL 6.199999809265137)
Descriptors: MW 458.42, ALogP 4.38, HBA 5, HBD 0, PSA 68.21, QED 0.54
Compound (SMILES): COc1cccc(-c2ccn[nH]2)c1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: CTMWEIJXXSCTJH-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 458.44, ALogP 4.18, HBA 5, HBD 1, PSA 80.34, QED 0.62
Compound (SMILES): COc1cccc(-c2ncccn2)c1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: YREUWZWUXFUQNJ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 470.45, ALogP 4.25, HBA 6, HBD 0, PSA 77.44, QED 0.56
Compound (SMILES): Cc1cnn(C)c1-c1ccccc1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: JHIBIGDVURAFGJ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 4399 nM (pChEMBL 5.360000133514404)
Descriptors: MW 456.47, ALogP 4.49, HBA 5, HBD 0, PSA 60.25, QED 0.58
Compound (SMILES): O=C(c1cccc2cc[nH]c12)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: BHDOEKBJNYFWML-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 401.39, ALogP 4.26, HBA 3, HBD 1, PSA 58.22, QED 0.71
Compound (SMILES): O=C(c1ccc(F)cc1-n1nccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: NOXUACCAWHVGCM-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 447.39, ALogP 3.5, HBA 6, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): O=C(c1cccc(F)c1Br)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: QSCWUOPMXMROKO-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: Receptor Radioligand Binding Assay: Human Orexin 2 Receptor:HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 459.24, ALogP 4.68, HBA 3, HBD 0, PSA 42.43, QED 0.63
Compound (SMILES): O=C(c1c(F)cccc1-c1ncccn1)N1CC2CC(Oc3ccc(Br)cn3)C1C2
InChIKey: DZJNFUJQJJPNEW-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 469.31, ALogP 4.12, HBA 5, HBD 0, PSA 68.21, QED 0.58
Compound (SMILES): O=C(c1cccc(F)c1-c1ncccn1)N1CC2CC(Oc3ccc(Br)cn3)C1C2
InChIKey: WHPVXNLPYOHPJB-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 469.31, ALogP 4.12, HBA 5, HBD 0, PSA 68.21, QED 0.58
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CC2CC(Oc3ccc(Br)cn3)C1C2
InChIKey: NLAPFONDAXCHAY-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 440.3, ALogP 3.11, HBA 6, HBD 0, PSA 73.14, QED 0.62
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CC3CC(Oc4ccc(Br)cn4)C2C3)n1
InChIKey: GOUAQCADINSCHG-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4x C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol).
Measurement: Ki = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 455.32, ALogP 2.81, HBA 7, HBD 0, PSA 86.03, QED 0.6
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CC2CC(Oc3ncccc3C(F)(F)F)C1C2
InChIKey: XPOSFFXHDZGZMB-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 294 nM (pChEMBL 6.53000020980835)
Descriptors: MW 429.4, ALogP 3.36, HBA 6, HBD 0, PSA 73.14, QED 0.64
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CC3CC(Oc4ncccc4C(F)(F)F)C2C3)n1
InChIKey: ZAUBOSKPBRXIFA-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4x C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol).
Measurement: Ki = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 444.42, ALogP 3.07, HBA 7, HBD 0, PSA 86.03, QED 0.61
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CC2CC(Nc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: YCPPLHONVRZFSC-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 428.42, ALogP 3.4, HBA 6, HBD 1, PSA 75.94, QED 0.69
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CC3CC(Nc4ccc(C(F)(F)F)cn4)C2C3)n1
InChIKey: DUSWDGIUZGEZMC-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4x C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol).
Measurement: Ki = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 443.43, ALogP 3.1, HBA 7, HBD 1, PSA 88.83, QED 0.67
Compound (SMILES): Cc1cccc(C(=O)N2CC3CC(Nc4ccc(C(F)(F)F)cn4)C2C3)c1-n1nccn1
InChIKey: TWMWEJVSFZPUFN-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 442.45, ALogP 3.7, HBA 6, HBD 1, PSA 75.94, QED 0.67
Compound (SMILES): CCOc1ccc2cccnc2c1C(=O)N1CC2CC(Nc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: UODSZXVZFBKAGJ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 456.47, ALogP 4.76, HBA 5, HBD 1, PSA 67.35, QED 0.6
Compound (SMILES): O=C(c1cc(F)ccc1-n1nccn1)N1CC2CC(Nc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: DMOGSWQIKPEGKH-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 446.41, ALogP 3.54, HBA 6, HBD 1, PSA 75.94, QED 0.62
Compound (SMILES): O=C(c1cc(F)ccc1-c1ncccn1)N1CC2CC(Nc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: CKIBODIXGNACEX-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Human Orexin 1 Receptor Ca2+ Mobilization Assay: CHO cells stably transfected with the human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12, 10% FBS, 1×pen-strep, 400 μg/ml G418. Cells were seeded on to 384-well Packard viewplates at a density of 10,000 cells/well and incubated overnight at 37° C., 5% CO2. The cells were dye-loaded with BD Calcium Assay kit (BD, cat #640178) in HBSS (Gibco, cat #14025-092) with 2.5 mM probenecid and incubated at 37° C., 5% CO2 for 45 min. Cells were pre-incubated with compounds (diluted in DMEM/F-12) for 15-30 minutes before agonist (orexin A, 10 nM) stimulation. Ligand-induced Ca2+ release was measured using a Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices, Sunnyvale, Calif.). Functional responses were measured as peak fluorescence intensity minus basal. The concentration of agonist that produced a half-maximal response is represented by the EC50 value. Antagonistic potency values were converted to apparent pKB values using a modified Cheng-Prusoff correction. Apparent pKB=−log IC50/1+[conc agonist/EC50].
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 457.43, ALogP 4.41, HBA 5, HBD 1, PSA 71.01, QED 0.59
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CC2CC(Nc3cnc(C(F)(F)F)cn3)C1C2
InChIKey: FFRFKFZPBDAESX-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 429.41, ALogP 2.79, HBA 7, HBD 1, PSA 88.83, QED 0.69
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1CNC(=O)[C@@H](N)Cc1ccccc1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CCN1CC1CC1)[C@H]2O5
InChIKey: WNIILMDFKJINIT-LZDVKRKESA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Binding Assay: ORL-1 Receptor Binding Assay Procedure: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Perkin Elmer, Shelton, Conn.) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 ml/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 mM at 4 C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/ml. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of the ORL-1 receptor membranes were stored at -80 C.Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (Perkin Elmer, Shelton, Conn.; 87.7 Ci/mmole) with 12 ug membrane protein in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4).
Measurement: Ki = 228.55 nM (pChEMBL 6.639999866485596)
Descriptors: MW 543.71, ALogP 3.3, HBA 6, HBD 3, PSA 97.05, QED 0.47