lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): [C-]#[N+]c1ccc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3CC#CC)N3CCN=C23)cc1
InChIKey: UPZODHXRHDMMSV-GOSISDBHSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 442.53, ALogP 2.22, HBA 7, HBD 1, PSA 87.35, QED 0.58
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3Cc3cc(F)ccc3F)N3CCN=C23)nc2ccccc12
InChIKey: DWBILHVCBQIJKX-HXUWFJFHSA-N
Target: Prolyl endopeptidase FAP (SINGLE PROTEIN), Homo sapiens
UniProt: Q12884
Assay: Inhibition of FAP (unknown origin) using Nle-Pro-AMC as substrate preincubated for 20 mins followed by substrate addition measured after 40 mins by fluorescence assay
Measurement: IC50 = 9920 nM (pChEMBL 5)
Descriptors: MW 557.61, ALogP 3.22, HBA 9, HBD 1, PSA 108.77, QED 0.4
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3Cc3cc(F)ccc3C#N)N3CCCN=C23)nc2ccccc12
InChIKey: YSYJCCSDMXIAMA-HSZRJFAPSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 99 nM (pChEMBL 7)
Descriptors: MW 578.66, ALogP 3.34, HBA 10, HBD 1, PSA 132.56, QED 0.38
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1nc(C)c3ccccc3n1)C1=NCCCN12
InChIKey: ZRWMIHVRYPKICQ-LJQANCHMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 497.61, ALogP 2.31, HBA 9, HBD 1, PSA 108.77, QED 0.55
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3C)N3CCN=C23)nc2ccccc12
InChIKey: GNDKRRZPFBIOFL-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 539 nM (pChEMBL 6.269999980926514)
Descriptors: MW 445.53, ALogP 1.43, HBA 9, HBD 1, PSA 108.77, QED 0.65
Compound (SMILES): CC(C)=CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1nc(C)c3ccccc3n1)C1=NCCN12
InChIKey: ZWKWPVARAOYCNW-LJQANCHMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 499.62, ALogP 2.86, HBA 9, HBD 1, PSA 108.77, QED 0.54
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3Cc3cccc(F)c3)N3CCN=C23)nc2ccccc12
InChIKey: PUUKUAAIHRSDSZ-OAQYLSRUSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 539.62, ALogP 3.08, HBA 9, HBD 1, PSA 108.77, QED 0.42
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3Cc3ccccc3)N3CCN=C23)nc2ccccc12
InChIKey: MNNYDJITSGUEIZ-OAQYLSRUSA-N
Target: Prolyl endopeptidase FAP (SINGLE PROTEIN), Homo sapiens
UniProt: Q12884
Assay: Inhibition of FAP (unknown origin) using Nle-Pro-AMC as substrate preincubated for 20 mins followed by substrate addition measured after 40 mins by fluorescence assay
Measurement: IC50 = 4640 nM (pChEMBL 5.329999923706055)
Descriptors: MW 521.63, ALogP 2.94, HBA 9, HBD 1, PSA 108.77, QED 0.43
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3CC3CC3)N3CCN=C23)nc2ccccc12
InChIKey: ZCLGDGHKXSQCOW-GOSISDBHSA-N
Target: Prolyl endopeptidase FAP (SINGLE PROTEIN), Homo sapiens
UniProt: Q12884
Assay: Inhibition of FAP (unknown origin) using Nle-Pro-AMC as substrate preincubated for 20 mins followed by substrate addition measured after 40 mins by fluorescence assay
Measurement: IC50 = 3122 nM (pChEMBL 5.510000228881836)
Descriptors: MW 485.6, ALogP 2.3, HBA 9, HBD 1, PSA 108.77, QED 0.59
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1ccc(OC)cc1)C1=NCCCN12
InChIKey: NMVRFVWHJJQLAA-LJQANCHMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 461.57, ALogP 2.06, HBA 8, HBD 1, PSA 92.22, QED 0.69
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)NC1=NCCCN12
InChIKey: RTUFWRJADRECCG-GFCCVEGCSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 6113 nM (pChEMBL 5.210000038146973)
Descriptors: MW 341.42, ALogP 0.14, HBA 7, HBD 2, PSA 91.78, QED 0.75
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1cccc3ccccc13)C1=NCCCN12
InChIKey: RIMHBNSDKFHPQR-JOCHJYFZSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 481.6, ALogP 3.21, HBA 7, HBD 1, PSA 82.99, QED 0.58
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1nccc(C#N)n1)C1=NCCN12
InChIKey: XQTUCZKSICNQRA-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 444.5, ALogP 0.33, HBA 10, HBD 1, PSA 132.56, QED 0.67
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1ccccc1C#N)C1=NCCN12
InChIKey: SCLSQCJVZCJCFD-LJQANCHMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 442.53, ALogP 1.54, HBA 8, HBD 1, PSA 106.78, QED 0.72
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3Cc3sccc3F)N3CCN=C23)nc2ccccc12
InChIKey: GRKJNKLGCBWLFP-QGZVFWFLSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 545.65, ALogP 3.14, HBA 10, HBD 1, PSA 108.77, QED 0.41
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3CC3CC3(F)F)N3CCN=C23)nc2ccccc12
InChIKey: HKOBPFKUFXOBBK-ZYMOGRSISA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 521.58, ALogP 2.55, HBA 9, HBD 1, PSA 108.77, QED 0.55
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3CC3CCC3)N3CCN=C23)nc2ccccc12
InChIKey: BFDQAZAVLYSIPZ-LJQANCHMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 499.62, ALogP 2.69, HBA 9, HBD 1, PSA 108.77, QED 0.57
Compound (SMILES): Cc1nc(CN2C(=O)c3c(nc(N4CCC[C@@H](N)C4)n3Cc3ccccc3C#N)N3CCN=C23)nc2ccccc12
InChIKey: DSAKKFXFAOKZAC-JOCHJYFZSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 546.64, ALogP 2.81, HBA 10, HBD 1, PSA 132.56, QED 0.4
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1C(=O)N(Cc1nc(C)c3ccccc3n1)C1=N[C@@H](C)CN12
InChIKey: ZNXHHGJSWDHYAH-PKOBYXMFSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Inhibition Assay : DPP4 activity was measured using a continuous fluorometric assay. The substrate, Gly-Pro-AMC, was cleaved by DPP4 to release the fluorescent AMC group. The reaction was monitored at the excitation wavelength of 360 nm and emission wavelength of 460 nm in a black 384-well plate using a PHERAstar Plus plate reader (BMG Labtech., Inc.) set at 37° C. The 30 μl assay solution contained 20 pM recombinant human DPP4 and 50 μM Gly-Pro-AMC substrate in assay buffer (100 mM HEPES, 100 mM NaCl, 0.1 mg/ml BSA, pH 7.5). The reaction was linear for at least 30 min (initial velocity) after addition of the substrate (no inhibitor control). All materials and reagents were pre-incubated at 37° C. prior to start of the experiment.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 497.61, ALogP 2.31, HBA 9, HBD 1, PSA 108.77, QED 0.55
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2ccc(NC(=O)[C@H]3CN4CCC3CC4)cc2)cc1
InChIKey: WRYXVNSFNTZSKG-FQEVSTJZSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. (Neuropharmacol. 1999, 38, 679-690). The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000×g, 4° C., 30 min). The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 μl (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 2.5 h. The non-specific binding is determined by incubation in the presence of 1 μM □-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine).
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 399.52, ALogP 3.01, HBA 4, HBD 2, PSA 78.51, QED 0.81
Compound (SMILES): O=C(Nc1ccc(-c2ccc(NS(=O)(=O)c3ccccc3)cc2)cc1)[C@H]1CN2CCC1CC2
InChIKey: QTXMZYJUSISXGH-VWLOTQADSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. (Neuropharmacol. 1999, 38, 679-690). The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000×g, 4° C., 30 min). The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 μl (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 2.5 h. The non-specific binding is determined by incubation in the presence of 1 μM □-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine).
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 461.59, ALogP 4.43, HBA 4, HBD 2, PSA 78.51, QED 0.57
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ccc(NC(=O)[C@H]3CN4CCC3CC4)cc2)cc1
InChIKey: ZHQNSRKFVGKLAO-IBGZPJMESA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. (Neuropharmacol. 1999, 38, 679-690). The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000×g, 4° C., 30 min). The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 μl (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 2.5 h. The non-specific binding is determined by incubation in the presence of 1 μM □-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine).
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 385.49, ALogP 2.28, HBA 4, HBD 2, PSA 92.5, QED 0.84
Compound (SMILES): O=C(Nc1ccc(-c2ccc(NC(=O)[C@H]3CN4CCC3CC4)cc2)cc1)NC1CCCC1
InChIKey: IEGHTUHBRDLAEZ-DEOSSOPVSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. (Neuropharmacol. 1999, 38, 679-690). The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000×g, 4° C., 30 min). The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 μl (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 2.5 h. The non-specific binding is determined by incubation in the presence of 1 μM □-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine).
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 432.57, ALogP 4.7, HBA 3, HBD 3, PSA 73.47, QED 0.64
Compound (SMILES): O=C(Nc1ccc(-c2ccc(NC(=O)[C@H]3CN4CCC3CC4)cc2)cc1)c1cccc(F)c1
InChIKey: QYIZSBHVENFHLS-VWLOTQADSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. (Neuropharmacol. 1999, 38, 679-690). The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000×g, 4° C., 30 min). The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 μl (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 2.5 h. The non-specific binding is determined by incubation in the presence of 1 μM □-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine).
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 443.52, ALogP 5.03, HBA 3, HBD 2, PSA 61.44, QED 0.58
Compound (SMILES): Cc1cc(OC(CCC(F)(F)F)c2ccc(C(=O)NCc3nnn[nH]3)cc2)cc(C)c1-c1ccc(C(C)(C)C)cc1
InChIKey: ZQTIEFGJUPAYBC-UHFFFAOYSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Binding Assay: The binding assays are carried out using a Scintillation Proximity Assay (Amersham) with WGA beads previously blocked with 1% fatty acid free BSA (ICN). The binding buffer contains 25 mM Hepes, pH 7.4, 2.5 mM CaCl2, 1 mM MgCl2, 0.1% fatty acid free BSA, (ICN), 0.003% tween-20, and Roche Complete Inhibitors without EDTA. Glucagon is dissolved in 0.01 N HCl at 1 mg/mL and immediately frozen at −80 degrees C. in 30 μl aliquots. The glucagon aliquot is diluted and used in binding assays within an hour. Test compounds are dissolved in DMSO and serially diluted in DMSO. 10 ul diluted compounds or DMSO is transferred into Corning 3632, opaque clear bottom assay plates containing 90 μl assay binding buffer or cold glucagon (NSB at 1 μM final). 50 μl of 1-125 glucagon (0.15 nM final in reaction), 50 μl of membranes (300 μg/well), and 40 μl of WGA beads (150 mgs/well) are added, covered, and mixed end over end.
Measurement: Ki = 63.4 nM (pChEMBL 7.199999809265137)
Descriptors: MW 565.64, ALogP 7.17, HBA 5, HBD 2, PSA 92.79, QED 0.22
Compound (SMILES): Cc1cc(OC(CCC(C)(C)C)c2ccc(C(=O)Nc3nnn[nH]3)cc2)cc(C)c1-c1ccc(C(F)(F)F)cc1
InChIKey: SGOVBKMRAJLULN-UHFFFAOYSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Binding Assay: The binding assays are carried out using a Scintillation Proximity Assay (Amersham) with WGA beads previously blocked with 1% fatty acid free BSA (ICN). The binding buffer contains 25 mM Hepes, pH 7.4, 2.5 mM CaCl2, 1 mM MgCl2, 0.1% fatty acid free BSA, (ICN), 0.003% tween-20, and Roche Complete Inhibitors without EDTA. Glucagon is dissolved in 0.01 N HCl at 1 mg/mL and immediately frozen at −80 degrees C. in 30 μl aliquots. The glucagon aliquot is diluted and used in binding assays within an hour. Test compounds are dissolved in DMSO and serially diluted in DMSO. 10 ul diluted compounds or DMSO is transferred into Corning 3632, opaque clear bottom assay plates containing 90 μl assay binding buffer or cold glucagon (NSB at 1 μM final). 50 μl of 1-125 glucagon (0.15 nM final in reaction), 50 μl of membranes (300 μg/well), and 40 μl of WGA beads (150 mgs/well) are added, covered, and mixed end over end.
Measurement: Ki = 93.3 nM (pChEMBL 7.03000020980835)
Descriptors: MW 551.61, ALogP 7.7, HBA 5, HBD 2, PSA 92.79, QED 0.23
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CCN(c3ccc4ccc(Cl)cc4n3)CC2)cc1F
InChIKey: LEBCYBIUSVYALI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 28.7 nM (pChEMBL 7.539999961853027)
Descriptors: MW 475.96, ALogP 5.23, HBA 5, HBD 1, PSA 71.01, QED 0.44
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CCN(c3ccc4ccc(F)cc4n3)CC2)cc1F
InChIKey: DLYLBQBKLQHKEF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 459.5, ALogP 4.71, HBA 5, HBD 1, PSA 71.01, QED 0.48
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CCN(c3ccc4ccccc4n3)CC2)cc1F
InChIKey: DWFAXOJYNLLLLH-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 441.51, ALogP 4.57, HBA 5, HBD 1, PSA 71.01, QED 0.5
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CCN(c3ccc4cc(F)ccc4n3)CC2)cc1F
InChIKey: WZEAPCRPXBGWOP-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 459.5, ALogP 4.71, HBA 5, HBD 1, PSA 71.01, QED 0.48
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CCN(c3ccc4cccc(F)c4n3)CC2)cc1F
InChIKey: DYHRIJWMZMUEHD-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 459.5, ALogP 4.71, HBA 5, HBD 1, PSA 71.01, QED 0.48
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ncc4ccccc4n3)C2)cc1F
InChIKey: XCTBRJCCTRHIJI-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 414.44, ALogP 3.19, HBA 6, HBD 1, PSA 83.9, QED 0.55
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ccc4ccccc4n3)C2)cc1F
InChIKey: LYQWROUQCSVXLE-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 413.46, ALogP 3.79, HBA 5, HBD 1, PSA 71.01, QED 0.55
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ccc4ccc(F)cc4n3)C2)cc1F
InChIKey: DFTZHTWXSASTML-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 431.45, ALogP 3.93, HBA 5, HBD 1, PSA 71.01, QED 0.53
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ncc4ccc(F)cc4n3)C2)cc1F
InChIKey: NPWHYCUJWVCDKS-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 432.43, ALogP 3.33, HBA 6, HBD 1, PSA 83.9, QED 0.53
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ncc4ccc(Cl)cc4n3)C2)cc1F
InChIKey: MLXZHNCPMBZZCF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 448.89, ALogP 3.84, HBA 6, HBD 1, PSA 83.9, QED 0.51
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ncc4cc(F)ccc4n3)C2)cc1F
InChIKey: WYLIHYRUCMLVLP-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 432.43, ALogP 3.33, HBA 6, HBD 1, PSA 83.9, QED 0.53
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ncc4cc(F)c(Cl)cc4n3)C2)cc1F
InChIKey: BTTPLKWZTJDMBV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 466.88, ALogP 3.98, HBA 6, HBD 1, PSA 83.9, QED 0.49
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ccc4cc(F)ccc4n3)C2)cc1F
InChIKey: JAJGVKKQUXUOSF-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 431.45, ALogP 3.93, HBA 5, HBD 1, PSA 71.01, QED 0.53
Compound (SMILES): CNC(=O)c1ccc(-c2nccnc2C2CN(c3ccc4ncc(Cl)cc4n3)C2)cc1F
InChIKey: IYDGGEUTAVPCGP-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 448.89, ALogP 3.84, HBA 6, HBD 1, PSA 83.9, QED 0.51
Compound (SMILES): NC(=O)c1ccc(-c2nccnc2C2CN(c3ccc4ccccc4n3)C2)cc1F
InChIKey: IXLQVIIYZMHIQJ-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 3304 nM (pChEMBL 5.480000019073486)
Descriptors: MW 399.43, ALogP 3.53, HBA 5, HBD 1, PSA 85, QED 0.57
Compound (SMILES): CNC(=O)c1cccc(-c2nccnc2C2CN(c3ccc4ccccc4n3)C2)c1
InChIKey: QJRPNOFJBOCSJG-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 2163 nM (pChEMBL 5.670000076293945)
Descriptors: MW 395.47, ALogP 3.66, HBA 5, HBD 1, PSA 71.01, QED 0.57
Compound (SMILES): NC(=O)c1ccc(-c2nccnc2C2CN(c3ccc4ccccc4n3)C2)cc1
InChIKey: PFAVUEZQRHCZTK-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET Assay: IMAP TR-FRET progressive binding system, FAM-cAMP substrate were from Molecular Devices (Sunnyvale, Calif.). The PDE IMAP assay was conducted in a 384-well black Greiner polypropylene plate (Sigma, St. Louis, Mo.). PDE inhibitors were serial diluted in 100% DMSO and dispensed into assay plate at 200 mL per well using Echo® Liquid Handling System from LABCYTE. Ten μL of PDE enzyme in IMAP reaction buffer (10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.01% Tween-20) was added into the assay wells. The PDE enzyme concentration used was based on each lot of enzyme activity, to ensure enzyme reaction falls in a linear range under assay condition. 1.4 nM of PDE2 or 8 μM PDE10 were used in the assay system. Enzyme was pre-incubated with inhibitors for 60 minutes at room temperature before addition of 10 uL of substrate addition, which results in 100 nM of FAM-cAMP in the reaction.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 381.44, ALogP 3.39, HBA 5, HBD 1, PSA 85, QED 0.59