lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC(=O)Nc1ccc2c(c1)CCCCc1ccc(cc1)C[C@H](NC(=O)/C=C/c1cc(Cl)ccc1-n1cnnn1)c1nc-2c[nH]1
InChIKey: XEKAKHSPWFHNNZ-FCPABOFRSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 623.12, ALogP 5.88, HBA 8, HBD 3, PSA 139.71, QED 0.21
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCc1nc(ccc1F)CC(NC(=O)/C=C/c1cc(Cl)ccc1C(C)=O)c1nc-2c[nH]1
InChIKey: SLXTVVGRZHVWMZ-QDEBKDIKSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 631.06, ALogP 5.64, HBA 7, HBD 4, PSA 155.17, QED 0.16
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCc1nc(ccc1F)CC(NC(=O)c1c(F)cc(C)cc1F)c1nc-2c[nH]1
InChIKey: QIKNPZZVNNZICR-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 578.55, ALogP 4.97, HBA 6, HBD 4, PSA 138.1, QED 0.27
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCc1nc(ccc1F)CC(NC(=O)[C@H]1CC[C@H](C)CC1)c1nc-2c[nH]1
InChIKey: ILYOESZRECBNAD-CCERHYJRSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki = 1309 nM (pChEMBL 5.880000114440918)
Descriptors: MW 548.62, ALogP 4.9, HBA 6, HBD 4, PSA 138.1, QED 0.37
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCc1nc(ccc1F)CC(NC(=O)/C=C/c1cc(Cl)ccc1-n1cnnn1)c1nc-2cn1C
InChIKey: LEKTYHNLYAWFRQ-QDEBKDIKSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 671.09, ALogP 4.43, HBA 11, HBD 3, PSA 170.84, QED 0.23
Compound (SMILES): CNc1ccc2c(c1)NC(=O)CCc1nc(ccc1F)CC(NC(=O)/C=C/c1cc(Cl)ccc1-n1cnnn1)c1nc-2c(Cl)[nH]1
InChIKey: CYKYWLCXBBYQIN-WTDSWWLTSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki = 7428 nM (pChEMBL 5.130000114440918)
Descriptors: MW 647.5, ALogP 4.93, HBA 9, HBD 4, PSA 155.4, QED 0.2
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCCC[C@H](NC(=O)/C=C/c1cc(Cl)ccc1-n1cnnn1)c1nc-2c[nH]1
InChIKey: RUNFYOCZSWNWFH-OJWOGGGRSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition. Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 576.02, ALogP 4.27, HBA 9, HBD 4, PSA 168.81, QED 0.26
Compound (SMILES): CC(C)c1ncc2c(=O)[nH]c3cc(Cl)ccc3n12
InChIKey: VJVYCJIULNTODR-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 261.71, ALogP 2.95, HBA 3, HBD 1, PSA 50.16, QED 0.73
Compound (SMILES): CC(C)c1ncc2c(=O)[nH]c3cc(C(=O)N(C)C)ccc3n12
InChIKey: AMPVKPFOYDLLCK-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 298.35, ALogP 2, HBA 4, HBD 1, PSA 70.47, QED 0.79
Compound (SMILES): COc1cc2c(cc1C(=O)N(C)C)[nH]c(=O)c1cnc(C3CCCCC3)n12
InChIKey: ZWNYSNVANDAZPD-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 368.44, ALogP 2.93, HBA 5, HBD 1, PSA 79.7, QED 0.77
Compound (SMILES): CCOc1cc2c(cc1C(=O)N(C)C)[nH]c(=O)c1cnc(C3CCCCC3)n12
InChIKey: UMWUUQQFTIUJRG-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 382.46, ALogP 3.32, HBA 5, HBD 1, PSA 79.7, QED 0.75
Compound (SMILES): CN(C)C(=O)c1cc2[nH]c(=O)c3cnc(C4CCCCC4)n3c2cc1Cl
InChIKey: WMOSXRMMUWZZPL-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 372.86, ALogP 3.58, HBA 4, HBD 1, PSA 70.47, QED 0.75
Compound (SMILES): O=C(c1cc2[nH]c(=O)c3cnc(C4CCCCC4)n3c2cc1Cl)N1CCN(CCO)CC1
InChIKey: HEKFKHONEGWJMR-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 457.96, ALogP 2.63, HBA 6, HBD 2, PSA 93.94, QED 0.63
Compound (SMILES): O=C(O)CCc1ncc2c(=O)[nH]c3cc(Br)ccc3n12
InChIKey: ZEDCCDVXWIERFN-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 336.15, ALogP 1.96, HBA 4, HBD 2, PSA 87.46, QED 0.77
Compound (SMILES): CCc1ccc2c(c1)[nH]c(=O)c1cnc(CCC(=O)O)n12
InChIKey: PKAAQRQMANZTPV-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 285.3, ALogP 1.76, HBA 4, HBD 2, PSA 87.46, QED 0.76
Compound (SMILES): O=C(O)CCc1ncc2c(=O)[nH]c3cc(C(F)(F)F)ccc3n12
InChIKey: UFPCPUIJYWTAEM-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 325.25, ALogP 2.21, HBA 4, HBD 2, PSA 87.46, QED 0.77
Compound (SMILES): O=C(O)/C=C/c1ccc2c(=O)[nH]c3cc(C(F)(F)F)ccc3n12
InChIKey: ZKGGCZGXEZKASH-ZZXKWVIFSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: To 150 uL of buffer B (70 mmol/L Tris-HCl, pH7.5, 16.7 mmol/L MgCl2, 33.3 nmol/L [3H]-cGMP) solution containing [3H]-cGMP (specific activity=244.2 GBq/mmol) at a concentration of 33.3 nmol/L, 50 uL of a solution of the compound to be evaluated (formed by dissolving the compound in DMSO and diluting it with distilled water to DMSO concentration of 5%) and 50 uL of the PDE9 protein solution as prepared in the above, as diluted with buffer C (40 mmol/L Tris-HCl, pH7.5, 15 mmol/L benzamidine, 15 mmol/L 2-mercaptoethanol, 1 ug/mL Pepstatin A, 1 ug/mL Leupeptin) by 1,500x, were added under cooling with ice. This mixed solution was incubated at 30 C. for 30 minutes and the enzymatic reaction of PDE9 was terminated by heating the system in boiling water for 90 seconds. Returning the system to room temperature, 50 uL of Snake venom (SIGMA: 1 mg/mL) was added, followed by 10 minutes' incubation at 30 C.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 322.24, ALogP 2.9, HBA 3, HBD 2, PSA 74.57, QED 0.71
Compound (SMILES): Cc1ccc(-c2c(-c3nn(C)c4ncnc(N5CCC5)c34)cnn2C)cc1
InChIKey: SCCSYDABXJGYAW-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 < 6.79 nM (pChEMBL 8.168000221252441)
Descriptors: MW 359.44, ALogP 2.95, HBA 7, HBD 0, PSA 64.66, QED 0.56
Compound (SMILES): Cn1ncc(-c2nn(C)c3ncnc(N4CC(F)C4)c23)c1-c1ccc(C2CC2)cc1
InChIKey: XJZABDREPNZAQR-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 < 1.31 nM (pChEMBL 8.883000373840332)
Descriptors: MW 403.47, ALogP 3.47, HBA 7, HBD 0, PSA 64.66, QED 0.52
Compound (SMILES): CCc1ccc(-n2cncc2-c2nn(C)c3ncnc(N4CC[C@@H](N(C)C)C4)c23)cc1
InChIKey: WGEDBIQFFXBVEU-GOSISDBHSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 416.53, ALogP 2.92, HBA 8, HBD 0, PSA 67.9, QED 0.5
Compound (SMILES): Cn1ncc(-c2nn(C)c3ncnc(N4CCC4)c23)c1-c1ccc(C(F)F)cc1
InChIKey: WGBSVRDVQHBPQJ-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 5.25 nM (pChEMBL 8.279999732971191)
Descriptors: MW 395.42, ALogP 3.58, HBA 7, HBD 0, PSA 64.66, QED 0.53
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC[C@@H](N(C)C)C5)c34)cnn2C)cc1
InChIKey: CRNMQZGODAGJNN-GOSISDBHSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 < 5.84 nM (pChEMBL 8.234000205993652)
Descriptors: MW 430.56, ALogP 3.13, HBA 8, HBD 0, PSA 67.9, QED 0.48
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC(F)C5)c34)cnn2C)cc1
InChIKey: JDMKZMZRNRRQDF-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 3.16 nM (pChEMBL 8.5)
Descriptors: MW 391.45, ALogP 3.15, HBA 7, HBD 0, PSA 64.66, QED 0.53
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CCC5)c34)cnn2C)cc1
InChIKey: MLERDBQFQWJIBU-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 1.64 nM (pChEMBL 8.789999961853027)
Descriptors: MW 373.46, ALogP 3.2, HBA 7, HBD 0, PSA 64.66, QED 0.55
Compound (SMILES): Cc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC(c6ccn(C)n6)C5)c34)cnn2C)cc1
InChIKey: MRPNSMNORVBWJU-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 6.33 nM (pChEMBL 8.199999809265137)
Descriptors: MW 439.53, ALogP 3.08, HBA 9, HBD 0, PSA 82.48, QED 0.43
Compound (SMILES): Cc1ccc(-c2c(-c3nn(C)c4ncnc(N5CCC(S(=O)(=O)C6CC6)C5)c34)cnn2C)cc1
InChIKey: LEQAMAVQEFXEOM-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 4.29 nM (pChEMBL 8.369999885559082)
Descriptors: MW 477.59, ALogP 2.9, HBA 9, HBD 0, PSA 98.8, QED 0.44
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CCC(S(C)(=O)=O)C5)c34)cnn2C)cc1
InChIKey: HQJXEKCFKZVKHI-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 7.08 nM (pChEMBL 8.149999618530273)
Descriptors: MW 465.58, ALogP 2.62, HBA 9, HBD 0, PSA 98.8, QED 0.45
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CCC(S(=O)(=O)N(C)C)C5)c34)cnn2C)cc1
InChIKey: VZBNLRIJKKIZTN-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 494.63, ALogP 2.46, HBA 9, HBD 0, PSA 102.04, QED 0.41
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC(c6ccn(C)n6)C5)c34)cnn2C)cc1
InChIKey: MRAFIYAYCCXWEC-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 4.47 nM (pChEMBL 8.350000381469727)
Descriptors: MW 453.55, ALogP 3.33, HBA 9, HBD 0, PSA 82.48, QED 0.41
Compound (SMILES): COC(=O)NC1CN(c2ncnc3c2c(-c2cnn(C)c2-c2ccc(C)cc2)nn3C)C1
InChIKey: OYNNREXPOYOAAM-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 9.89 nM (pChEMBL 8.010000228881836)
Descriptors: MW 432.49, ALogP 2.28, HBA 9, HBD 1, PSA 102.99, QED 0.53
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC[C@H](NC(C)=O)C5)c34)cnn2C)cc1
InChIKey: JGDAUMIXIUXNIR-SFHVURJKSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 9.87 nM (pChEMBL 8.010000228881836)
Descriptors: MW 444.54, ALogP 2.71, HBA 8, HBD 1, PSA 93.76, QED 0.51
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC(NC(=O)OC)C5)c34)cnn2C)cc1
InChIKey: RAYJVXURIYGMSY-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 5.48 nM (pChEMBL 8.260000228881836)
Descriptors: MW 446.52, ALogP 2.54, HBA 9, HBD 1, PSA 102.99, QED 0.5
Compound (SMILES): COc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC(NC(=O)OC(C)(C)C)C5)c34)cnn2C)cc1
InChIKey: GOCMPYZGHHOJBN-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 9.34 nM (pChEMBL 8.029999732971191)
Descriptors: MW 490.57, ALogP 3.15, HBA 10, HBD 1, PSA 112.22, QED 0.45
Compound (SMILES): Cn1ccc(C2CN(c3ncnc4c3c(-c3cnn(C)c3-c3ccc(Cl)c(F)c3)nn4C)C2)n1
InChIKey: NODIDANHSRWCTM-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 < 2.87 nM (pChEMBL 8.541999816894531)
Descriptors: MW 477.94, ALogP 3.56, HBA 9, HBD 0, PSA 82.48, QED 0.39
Compound (SMILES): CN(C)S(=O)(=O)C1CCN(c2ncnc3c2c(-c2cnn(C)c2-c2ccc(Cl)c(F)c2)nn3C)C1
InChIKey: IMRHJXOHXUVYEY-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 3.59 nM (pChEMBL 8.449999809265137)
Descriptors: MW 519.01, ALogP 2.69, HBA 9, HBD 0, PSA 102.04, QED 0.4
Compound (SMILES): COc1ccc(-c2c(-c3nn(C)c4ncnc(-c5ccn(N)n5)c34)cnn2C)cc1F
InChIKey: FJSIXZSCBKBVQQ-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 9.47 nM (pChEMBL 8.020000457763672)
Descriptors: MW 419.42, ALogP 2.16, HBA 10, HBD 1, PSA 114.49, QED 0.44
Compound (SMILES): Cn1ncc(-c2nn(C)c3ncnc(N4CCC(S(=O)(=O)CC5CC5)C4)c23)c1-c1ccc(Cl)c(F)c1
InChIKey: WPHAWSOFZZNEJI-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Scintillation Proximity Assay: In the present assay, the activity of the test substances on human full-length PDE2A3 enzyme was determined using the [3H]-cGMP scintillation proximity assay (SPA) modified from the Amersham TRKQ7100 instructions (GE Healthcare, Arlington Heights, Ill., USA). PDE2A3 protein was obtained from FLAG purification of sf21 insect cells using standard affinity purification procedures for this tag (anti-FLAG M2, Sigma Aldrich, St. Louis, Mo., USA). Briefly, the SPA assays were performed using PDE SPA yttrium silicate beads (Perkin Elmer RPNQ0024; PerkinElmer, Inc., Waltham, Mass., USA) which bind preferentially to the linear nucleotide, GMP, compared to the cyclic nucleotide, cGMP. The, 3H-GMP product was detected using a Wallac MicroBeta scintillation counter. The reaction time was chosen with respect to the amount of time in which 10-20% of substrate was hydrolyzed by the enzyme. The assay was validated using PDE2-selective literature compounds.
Measurement: IC50 = 9.89 nM (pChEMBL 8.010000228881836)
Descriptors: MW 530.03, ALogP 3.63, HBA 9, HBD 0, PSA 98.8, QED 0.38