lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): [C-]#[N+]c1cccc([C@@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ccc54)C[C@H]3CO2)c1C
InChIKey: VCMCFFKBVWQCLM-FLOOPIEZSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 470.54, ALogP 2.23, HBA 8, HBD 0, PSA 93.63, QED 0.54
Compound (SMILES): Cc1c([C@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@H]3CS2)ccc2c1COC2=O
InChIKey: NNNUGBUDVVUHRD-MDGGQCKNSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37 C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 517.62, ALogP 2.07, HBA 10, HBD 0, PSA 106.34, QED 0.48
Compound (SMILES): [C-]#[N+]c1c(OC)ccc([C@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@@H]3CO2)c1C
InChIKey: XOBWXKWLNFYMLG-ZBOFDPRTSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 500.56, ALogP 2.24, HBA 9, HBD 0, PSA 102.86, QED 0.5
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4Cc5cnc(-n6cnnn6)nc5C4)C[C@@H]3CO2)c1C
InChIKey: FKMWVXBCDWWRBS-IDLMPWNNSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 489.52, ALogP 1.45, HBA 9, HBD 0, PSA 106.52, QED 0.51
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@H]2CN3CCN(C(=O)C4Cc5cnc(-n6cnnn6)nc5C4)C[C@H]3CO2)c1C
InChIKey: FKMWVXBCDWWRBS-GPIDFBCLSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 489.52, ALogP 1.45, HBA 9, HBD 0, PSA 106.52, QED 0.51
Compound (SMILES): [C-]#[N+]c1cc([C@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ccc54)C[C@@H]3CO2)c(F)cc1OC
InChIKey: KTJYUESWBDTEQG-SWNJZGHLSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 504.53, ALogP 2.07, HBA 9, HBD 0, PSA 102.86, QED 0.5
Compound (SMILES): O=C1OCCc2c1ccc([C@@H]1CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ccc54)C[C@H]3CO1)c2F
InChIKey: WRTPQTJWYSLXQR-YXHQUHRKSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 519.54, ALogP 1.22, HBA 10, HBD 0, PSA 115.57, QED 0.47
Compound (SMILES): [C-]#[N+]c1cc([C@@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ncc54)C[C@H]3CO2)ccc1F
InChIKey: UYACTOHYTKXHNZ-BTLCHPSKSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 475.49, ALogP 1.46, HBA 9, HBD 0, PSA 106.52, QED 0.52
Compound (SMILES): [C-]#[N+]c1cc([C@@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ncc54)C[C@@H]3CO2)ccc1F
InChIKey: UYACTOHYTKXHNZ-RWPZGMTISA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 475.49, ALogP 1.46, HBA 9, HBD 0, PSA 106.52, QED 0.52
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ncc54)C[C@@H]3CO2)c1Cl
InChIKey: KWBYMUBAIAICGT-QWYDSHIESA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37 C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 509.93, ALogP 2.11, HBA 9, HBD 0, PSA 106.52, QED 0.49
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ncc54)C[C@@H]3CO2)c1Cl
InChIKey: KWBYMUBAIAICGT-BOOUNLCJSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 509.93, ALogP 2.11, HBA 9, HBD 0, PSA 106.52, QED 0.49
Compound (SMILES): C[C@H]1Cc2c(ccc([C@@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@@H]4CO3)c2F)C(=O)O1
InChIKey: SOSQLHPGHQRBCR-HMEYJTGQSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37 C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 533.56, ALogP 1.61, HBA 10, HBD 0, PSA 115.57, QED 0.46
Compound (SMILES): C[C@H]1Cc2c(ccc([C@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@@H]4CO3)c2F)C(=O)O1
InChIKey: SOSQLHPGHQRBCR-NKKMHXQMSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 533.56, ALogP 1.61, HBA 10, HBD 0, PSA 115.57, QED 0.46
Compound (SMILES): C[C@H]1Cc2c(ccc([C@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@H]4CO3)c2F)C(=O)O1
InChIKey: SOSQLHPGHQRBCR-LJHDBQRISA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 533.56, ALogP 1.61, HBA 10, HBD 0, PSA 115.57, QED 0.46
Compound (SMILES): C[C@H]1Cc2c(ccc([C@@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@H]4CO3)c2F)C(=O)O1
InChIKey: SOSQLHPGHQRBCR-PKQDRTFPSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 533.56, ALogP 1.61, HBA 10, HBD 0, PSA 115.57, QED 0.46
Compound (SMILES): C[C@@H]1Cc2c(ccc([C@@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@@H]4CO3)c2F)C(=O)O1
InChIKey: SOSQLHPGHQRBCR-DQSLTDSHSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 533.56, ALogP 1.61, HBA 10, HBD 0, PSA 115.57, QED 0.46
Compound (SMILES): C[C@@H]1Cc2c(ccc([C@@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@H]4CO3)c2F)C(=O)O1
InChIKey: SOSQLHPGHQRBCR-XDHOFOIASA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 533.56, ALogP 1.61, HBA 10, HBD 0, PSA 115.57, QED 0.46
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)cnc54)C[C@@H]3CO2)c1C
InChIKey: HZNNIDAPNRQITQ-PJDJYQKSSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 488.53, ALogP 2.37, HBA 8, HBD 0, PSA 93.63, QED 0.52
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@H]3CS2)c1C
InChIKey: BIXAMJUQSVEREZ-RLPNNEDTSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 504.6, ALogP 3.09, HBA 8, HBD 0, PSA 84.4, QED 0.51
Compound (SMILES): [C-]#[N+]c1ccc([C@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@H]3CO2)c(C)c1F
InChIKey: FLDUIMICEOVVQD-JJKBQAIRSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 488.53, ALogP 2.37, HBA 8, HBD 0, PSA 93.63, QED 0.52
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@H]3CN2)c1C
InChIKey: IIZMZERPGJMMLW-KKGGMLHBSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 487.54, ALogP 1.94, HBA 8, HBD 1, PSA 96.43, QED 0.56
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@H]3CN2)c1C
InChIKey: IIZMZERPGJMMLW-MVPHGSNYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 487.54, ALogP 1.94, HBA 8, HBD 1, PSA 96.43, QED 0.56
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ccc54)C[C@H]3CN2)c1C
InChIKey: QYTGXCCUHMQTDO-QXGTWOLJSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 487.54, ALogP 1.94, HBA 8, HBD 1, PSA 96.43, QED 0.56
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)cnc54)C[C@H]3CN2)c1C
InChIKey: ZIBROJNRLAFASA-PJDJYQKSSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37 C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 487.54, ALogP 1.94, HBA 8, HBD 1, PSA 96.43, QED 0.56
Compound (SMILES): Cc1c([C@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@H]3CN2)ccc2c1COC2=O
InChIKey: KAIVPFKYDYSHMJ-QKLBRSPYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 500.56, ALogP 0.92, HBA 10, HBD 1, PSA 118.37, QED 0.52
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@H]2CN3CCN(C(=O)C4CCc5nc(-n6cnnn6)ncc54)C[C@H]3CN2)c1C
InChIKey: BNDARHVEYNVOHK-IKZMBGHXSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 488.53, ALogP 1.34, HBA 9, HBD 1, PSA 109.32, QED 0.55
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@@H]3CN2)c1C
InChIKey: IIZMZERPGJMMLW-JJKBQAIRSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37 C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 487.54, ALogP 1.94, HBA 8, HBD 1, PSA 96.43, QED 0.56
Compound (SMILES): [C-]#[N+]c1c(F)ccc([C@@H]2CN3CCN(C(=O)C4CCc5cc(-n6cnnn6)ncc54)C[C@@H]3CN2)c1C
InChIKey: IIZMZERPGJMMLW-RLPNNEDTSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37 C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37 C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 487.54, ALogP 1.94, HBA 8, HBD 1, PSA 96.43, QED 0.56
Compound (SMILES): C[C@H]1Cc2cc([C@H]3CN4CCN(C(=O)C5CCc6nc(-n7cnnn7)ccc65)C[C@H]4CO3)ccc2C(=O)O1
InChIKey: ZQXLHKNJQHWMKP-BCKPUZMFSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Thallium Flux Assay: The ROMK channel functional thallium flux assay is performed in 384 wells, using the FLIPR-Tetra instrument. HEK-hKir1.1 cells are seeded in Poly-D-Lysine microplates and kept in a 37 C.-10% CO2 incubator overnight. On the day of the experiment, the growth media is replaced with the FluxOR reagent loading buffer and incubated, protected from light, at ambient temperature (23-25 C.) for 90 min. The loading buffer is replaced with assay buffer+/-test compound followed by 30 min incubation at ambient temperature, where the Thallium/Potassium stimulant is added to the microplate.Step Protocol  1. Seed HEK-hKir1.1 cells (50 ul at 20,000 cells/well) in 384-well PDL coated Microplates  2. Allow cells to adhere overnight in humidified 37 C./10% CO2 incubator  3. Completely remove cell growth media from microplate and replace with 25 ul loading buffer  4. Incubate Microplate at room temperature, protected form light, for 90 min  5.
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 515.57, ALogP 1.47, HBA 10, HBD 0, PSA 115.57, QED 0.48
Compound (SMILES): O=C(c1cc(F)ccc1-c1ncccn1)N1C2CCC1C(COc1ccccn1)C2
InChIKey: NUFXKJOWPLPSAQ-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 NM001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM001526) 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 (2K xG, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -800 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 404.45, ALogP 3.75, HBA 5, HBD 0, PSA 68.21, QED 0.65
Compound (SMILES): Cc1ccc(-c2ncccn2)c(C(=O)N2C3CCC2C(COc2ccccn2)C3)n1
InChIKey: WKBJARZMMUKHBI-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 NM001526) 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 (2K xG, 5 min at 40 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 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 401.47, ALogP 3.31, HBA 6, HBD 0, PSA 81.1, QED 0.65
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C3CCC2C(COc2ccccn2)C3)n1
InChIKey: SPNVMISESJDLQJ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM001526) 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 (2K xG, 5 min at 40 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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 390.45, ALogP 2.44, HBA 7, HBD 0, PSA 86.03, QED 0.67
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C3CCC2C(COc2ccc(F)cn2)C3)n1
InChIKey: WGJDXEJAXMDTDU-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM001526) 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 (2K xG, 5 min at 40 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 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.44, ALogP 2.58, HBA 7, HBD 0, PSA 86.03, QED 0.65
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C3CCC2C(COc2ccc(F)cn2)C3)c1
InChIKey: FNSBFXNNFNCHOW-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 NM001526) 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 (2K xG, 5 min at 40 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 = 32 nM (pChEMBL 7.5)
Descriptors: MW 407.45, ALogP 3.18, HBA 6, HBD 0, PSA 73.14, QED 0.65
Compound (SMILES): O=C(c1ccccc1-c1cccs1)N1C2CCC1C(COc1ccc(F)cn1)C2
InChIKey: JIEFEDOEWSOKJT-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 NM001526) 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 (2K xG, 5 min at 40 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 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 408.5, ALogP 5.02, HBA 4, HBD 0, PSA 42.43, QED 0.6
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C3CCC2C(COc2nccc(C(F)(F)F)n2)C3)c1
InChIKey: YAXZYROJSIUFJX-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 NM001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM001526) 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 (2K xG, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -800 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 458.44, ALogP 3.46, HBA 7, HBD 0, PSA 86.03, QED 0.58