lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(NC(=O)c2cnn3ccc(N4CCC[C@@H]4c4cc(F)cn(C)c4=O)nc23)cn1
InChIKey: SICRRVUVAIRMQG-LJQANCHMSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 447.47, ALogP 2.86, HBA 8, HBD 1, PSA 97.42, QED 0.52
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)NC4CCC4)c3n2)c1=O
InChIKey: KKQVKLFNDUPHNK-QGZVFWFLSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 665.6 nM (pChEMBL 6.179999828338623)
Descriptors: MW 410.45, ALogP 2.19, HBA 7, HBD 1, PSA 84.53, QED 0.71
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)Nc4cccnc4)c3n2)c1=O
InChIKey: XURYENAZODILKN-GOSISDBHSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 433.45, ALogP 2.56, HBA 8, HBD 1, PSA 97.42, QED 0.53
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)NCC4CC4)c3n2)c1=O
InChIKey: CTGZXMASDOJLIY-QGZVFWFLSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 410.45, ALogP 2.05, HBA 7, HBD 1, PSA 84.53, QED 0.7
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)N[C@H](CO)C(C)(C)C)c3n2)c1=O
InChIKey: DXCATLCGJNNZIB-QZTJIDSGSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.52, ALogP 2.05, HBA 8, HBD 2, PSA 104.76, QED 0.61
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)N[C@@H]4CCCC[C@H]4O)c3n2)c1=O
InChIKey: GNHQMDGKASSYQR-GUDVDZBRSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.51, ALogP 1.94, HBA 8, HBD 2, PSA 104.76, QED 0.62
Compound (SMILES): C[C@@H](NC(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)cn(C)c3=O)nc12)C1CC1
InChIKey: ISCJKTYZQXHEBM-FZKQIMNGSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 = 311 nM (pChEMBL 6.510000228881836)
Descriptors: MW 424.48, ALogP 2.44, HBA 7, HBD 1, PSA 84.53, QED 0.68
Compound (SMILES): C[C@H](NC(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)cn(C)c3=O)nc12)C1CC1
InChIKey: ISCJKTYZQXHEBM-SCLBCKFNSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 = 419 nM (pChEMBL 6.380000114440918)
Descriptors: MW 424.48, ALogP 2.44, HBA 7, HBD 1, PSA 84.53, QED 0.68
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)NC4(C)CC4)c3n2)c1=O
InChIKey: DGVVSWFLMBWPNY-MRXNPFEDSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 616 nM (pChEMBL 6.210000038146973)
Descriptors: MW 410.45, ALogP 2.19, HBA 7, HBD 1, PSA 84.53, QED 0.71
Compound (SMILES): Cn1cc(F)cc([C@H]2CCCN2c2ccn3ncc(C(=O)Nc4ccc(F)cn4)c3n2)c1=O
InChIKey: OSIRKNSRCSGLDC-QGZVFWFLSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: TrkA ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 μM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking. The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 μg/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL). After the addition of 1M phosphoric acid, the chromogenic substrate color intensity was quantitated via absorbance at 450 nm. IC50 values were calculated using either a 4 or 5-parameter logistic curve fit.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 451.44, ALogP 2.7, HBA 8, HBD 1, PSA 97.42, QED 0.51
Compound (SMILES): COc1ncc(F)cc1[C@H]1CCCN1c1ccn2ncc(C(=O)Nc3ccn(C)n3)c2n1
InChIKey: SPBLOIGTOGQHKL-MRXNPFEDSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia® Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 21.8 nM (pChEMBL 7.659999847412109)
Descriptors: MW 436.45, ALogP 2.6, HBA 9, HBD 1, PSA 102.47, QED 0.51
Compound (SMILES): COc1ncc(F)cc1[C@H]1CCCN1c1ccn2ncc(C(=O)Nc3cc(C4CC4)n[nH]3)c2n1
InChIKey: HRXHRVGEOCMYJD-GOSISDBHSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 462.49, ALogP 3.47, HBA 8, HBD 2, PSA 113.33, QED 0.45
Compound (SMILES): COc1ncc(F)cc1[C@H]1CCCN1c1ccn2ncc(C(=O)Nc3ccn(C(C)C)n3)c2n1
InChIKey: YHWLSZUFSOTFQF-GOSISDBHSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 38.2 nM (pChEMBL 7.420000076293945)
Descriptors: MW 464.51, ALogP 3.64, HBA 9, HBD 1, PSA 102.47, QED 0.46
Compound (SMILES): CCCCOC(=O)CCC(=O)N[C@@H](CC(=O)O)Cc1ccc(-c2cccc(Cl)c2)cc1
InChIKey: JZPSPJKNLFZTJU-OAQYLSRUSA-N
Target: Membrane metallo-endopeptidase-like 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q495T6
Assay: Inhibition Assay: Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 μM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 μM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 445.94, ALogP 4.63, HBA 4, HBD 2, PSA 92.7, QED 0.37
Compound (SMILES): O=C(O)CCC(=O)N[C@@H](CC(=O)O)Cc1ccc(-c2cccc(F)c2)cc1
InChIKey: GKNJPJZPAMDYBU-QGZVFWFLSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: Inhibition of recombinant human NEP expressed in insect cells preincubated for 1 hr using Cys(PT14)-Arg-Arg-Leu-Trp-OH as substrate and measured after 1 hr by fluorescence based assay
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 373.38, ALogP 2.86, HBA 3, HBD 3, PSA 103.7, QED 0.63
Compound (SMILES): COc1ccccc1-c1ccc(C[C@H](CC(=O)O)NC(=O)CCC(=O)O)cc1
InChIKey: KNWZFVOURZCFAD-MRXNPFEDSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: Inhibition of recombinant human NEP expressed in insect cells preincubated for 1 hr using Cys(PT14)-Arg-Arg-Leu-Trp-OH as substrate and measured after 1 hr by fluorescence based assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 385.42, ALogP 2.73, HBA 4, HBD 3, PSA 112.93, QED 0.58
Compound (SMILES): COc1ccc(Cl)cc1-c1ccc(C[C@H](CC(=O)O)NC(=O)CCC(=O)O)cc1
InChIKey: QLCPDIVEFVTPQJ-MRXNPFEDSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: Inhibition of recombinant human NEP expressed in insect cells preincubated for 1 hr using Cys(PT14)-Arg-Arg-Leu-Trp-OH as substrate and measured after 1 hr by fluorescence based assay
Measurement: IC50 = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 419.86, ALogP 3.38, HBA 4, HBD 3, PSA 112.93, QED 0.54
Compound (SMILES): O=C(O)CCC(=O)N[C@@H](CC(=O)O)Cc1ccc(-c2cccc(Cl)c2)cc1
InChIKey: ZBGYPMPWJWNWEA-QGZVFWFLSA-N
Target: Membrane metallo-endopeptidase-like 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q495T6
Assay: Inhibition Assay: Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 μM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 μM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 389.83, ALogP 3.37, HBA 3, HBD 3, PSA 103.7, QED 0.61
Compound (SMILES): O=C(O)CCC(=O)N[C@@H](CC(=O)O)Cc1ccc(-c2ccccc2)cc1
InChIKey: XBIYMMZPQYOOJC-QGZVFWFLSA-N
Target: Membrane metallo-endopeptidase-like 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q495T6
Assay: Inhibition Assay: Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 μM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 μM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 355.39, ALogP 2.72, HBA 3, HBD 3, PSA 103.7, QED 0.64
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 = 107 nM (pChEMBL 6.96999979019165)
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 VII (SINGLE PROTEIN), Homo sapiens
UniProt: P08709
Assay: Inhibition of human coagulation factor 7a using H-(D)-Ile-Pro-Arg-pNA as substrate after 10 to 120 mins at 25 degC by spectrophotometric method
Measurement: Ki = 3190 nM (pChEMBL 5.5)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 = 1259 nM (pChEMBL 5.900000095367432)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 = 7544 nM (pChEMBL 5.119999885559082)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 = 2814 nM (pChEMBL 5.550000190734863)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 = 6371 nM (pChEMBL 5.199999809265137)
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: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition Assay: By a method similar to the measurement of PDE9-inhibiting activity, PDE5-inhibiting activity of each of the test compounds was measured, percent inhibition was calculated and IC50 value against PDE5 was determined. 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.
Measurement: IC50 = 4561 nM (pChEMBL 5.340000152587891)
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: Inhibition of full length recombinant human FLAG-tagged PDE2A3 expressed in sf21 cells using [3H]cGMP as substrate by scintillation proximity assay
Measurement: IC50 = 17.7 nM (pChEMBL 7.75)
Descriptors: MW 359.44, ALogP 2.95, HBA 7, HBD 0, PSA 64.66, QED 0.56
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: Inhibition of full length recombinant human FLAG-tagged PDE2A3 expressed in sf21 cells using [3H]cGMP as substrate by scintillation proximity assay
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 430.56, ALogP 3.13, HBA 8, HBD 0, PSA 67.9, QED 0.48
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: Inhibition of full length recombinant human FLAG-tagged PDE2A3 expressed in sf21 cells using [3H]cGMP as substrate by scintillation proximity assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 373.46, ALogP 3.2, HBA 7, HBD 0, PSA 64.66, QED 0.55
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: Inhibition of full length recombinant human FLAG-tagged PDE2A3 expressed in sf21 cells using [3H]cGMP as substrate by scintillation proximity assay
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 446.52, ALogP 2.54, HBA 9, HBD 1, PSA 102.99, QED 0.5
Compound (SMILES): CCc1ccc(-c2c(-c3nn(C)c4ncnc(N5CC(OC)C5)c34)cnn2C)cc1
InChIKey: PKEUSYAXAXEPBM-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of full length recombinant human FLAG-tagged PDE2A3 expressed in sf21 cells using [3H]cGMP as substrate by scintillation proximity assay
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 403.49, ALogP 2.83, HBA 8, HBD 0, PSA 73.89, QED 0.51
Compound (SMILES): CNc1ncnc2c1c(-c1cnn(C)c1-c1ccc(C(F)(F)F)cc1)nn2C
InChIKey: RCPKOFJPUJIKJL-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 = 13.7 nM (pChEMBL 7.860000133514404)
Descriptors: MW 387.37, ALogP 3.49, HBA 7, HBD 1, PSA 73.45, QED 0.58
Compound (SMILES): N[C@H]1CCCN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C1
InChIKey: DRSGGAHSPDXOOW-LBPRGKRZSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 415.47, ALogP 3.66, HBA 6, HBD 2, PSA 84.14, QED 0.68
Compound (SMILES): N[C@@H]1CN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)CC[C@H]1O
InChIKey: LQASHUDUJOBHMP-CXAGYDPISA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 431.47, ALogP 2.63, HBA 7, HBD 3, PSA 104.37, QED 0.59
Compound (SMILES): N[C@@H]1CN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)CC[C@H]1F
InChIKey: QQRNXNZMTIFVNK-BXUZGUMPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 433.46, ALogP 3.61, HBA 6, HBD 2, PSA 84.14, QED 0.66
Compound (SMILES): N[C@H]1C[C@@H](O)CN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C1
InChIKey: PRLYAWMVWDZNRR-NWDGAFQWSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 431.47, ALogP 2.63, HBA 7, HBD 3, PSA 104.37, QED 0.59
Compound (SMILES): N[C@@H]1CN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)CC[C@@H]1O
InChIKey: LQASHUDUJOBHMP-DYVFJYSZSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 431.47, ALogP 2.63, HBA 7, HBD 3, PSA 104.37, QED 0.59
Compound (SMILES): COC1CCN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)CC1N
InChIKey: RWRRKKBGTAZXGP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 243 nM (pChEMBL 6.610000133514404)
Descriptors: MW 445.5, ALogP 3.29, HBA 7, HBD 2, PSA 93.37, QED 0.63
Compound (SMILES): CO[C@@H]1C[C@H](N)CN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C1
InChIKey: WXIKUAVDMWNARE-QWHCGFSZSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 piper well. To start the reaction, 10 μl of 10 nM Pim2 kinase and 20 μM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, and 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 μl of 8 μM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 μM ATP, 10 μM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 μl KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 445.5, ALogP 3.29, HBA 7, HBD 2, PSA 93.37, QED 0.63