lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(C(N)=O)cc1-c1nncc2nc(Oc3ccc(F)cc3)ccc12
InChIKey: DZIGXCDENKQNHR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Biological Assay: Kinase reaction buffer for p38alpha HTRF assays consists of 50 mM Tris-pH 7.5, 5 mM MgCl2, 0.1 mg/mL BSA, 100 uM Na3VO4 and 0.5 mM DTT. HTRF Detection Buffer:HTRF detection buffer contains 100 mM HEPES-pH 7.5, 100 mM NaCl, 0.1% BSA, 0.05% Tween-20, and 10 mM EDTA. Serial Dilution of Compounds: Compounds were dissolved in 100% DMSO and serially diluted (3 fold, 10 point) in a polypropylene 96-well microtiter plate (drug plate). The final starting concentration of compounds in the p38alpha enzymatic assays was 1 uM. Columns 6 and 12 (HI controls and LO controls respectively) in the drug plate were reserved as controls and contained only DMSO.Kinase Reaction: The p38alpha kinase reactions were carried out in a polypropylene 96-well black round bottom assay plate in total volume of 30 uL kinase reaction buffer.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 374.38, ALogP 4.03, HBA 5, HBD 1, PSA 90.99, QED 0.58
Compound (SMILES): Cc1noc(C)c1-c1nncc2nc(Oc3ccc(F)cc3F)ccc12
InChIKey: GEISKBROGLLIKZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Biological Assay: Kinase reaction buffer for p38alpha HTRF assays consists of 50 mM Tris-pH 7.5, 5 mM MgCl2, 0.1 mg/mL BSA, 100 uM Na3VO4 and 0.5 mM DTT. HTRF Detection Buffer:HTRF detection buffer contains 100 mM HEPES-pH 7.5, 100 mM NaCl, 0.1% BSA, 0.05% Tween-20, and 10 mM EDTA. Serial Dilution of Compounds: Compounds were dissolved in 100% DMSO and serially diluted (3 fold, 10 point) in a polypropylene 96-well microtiter plate (drug plate). The final starting concentration of compounds in the p38alpha enzymatic assays was 1 uM. Columns 6 and 12 (HI controls and LO controls respectively) in the drug plate were reserved as controls and contained only DMSO.Kinase Reaction: The p38alpha kinase reactions were carried out in a polypropylene 96-well black round bottom assay plate in total volume of 30 uL kinase reaction buffer.
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 354.32, ALogP 4.37, HBA 6, HBD 0, PSA 73.93, QED 0.54
Compound (SMILES): Cc1cc(F)ccc1Oc1ccc2c(-c3ccccc3C)nncc2n1
InChIKey: RCXHFYUMRAIQDJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Biological Assay: Kinase reaction buffer for p38alpha HTRF assays consists of 50 mM Tris-pH 7.5, 5 mM MgCl2, 0.1 mg/mL BSA, 100 uM Na3VO4 and 0.5 mM DTT. HTRF Detection Buffer:HTRF detection buffer contains 100 mM HEPES-pH 7.5, 100 mM NaCl, 0.1% BSA, 0.05% Tween-20, and 10 mM EDTA. Serial Dilution of Compounds: Compounds were dissolved in 100% DMSO and serially diluted (3 fold, 10 point) in a polypropylene 96-well microtiter plate (drug plate). The final starting concentration of compounds in the p38alpha enzymatic assays was 1 uM. Columns 6 and 12 (HI controls and LO controls respectively) in the drug plate were reserved as controls and contained only DMSO.Kinase Reaction: The p38alpha kinase reactions were carried out in a polypropylene 96-well black round bottom assay plate in total volume of 30 uL kinase reaction buffer.
Measurement: IC50 = 168 nM (pChEMBL 6.78000020980835)
Descriptors: MW 345.38, ALogP 5.24, HBA 4, HBD 0, PSA 47.9, QED 0.51
Compound (SMILES): Cc1cc(F)ccc1Oc1ccc2c(-c3cc(C(N)=O)ccc3C)nncc2n1
InChIKey: FGPHNSWRZKDUOC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Biological Assay: Kinase reaction buffer for p38alpha HTRF assays consists of 50 mM Tris-pH 7.5, 5 mM MgCl2, 0.1 mg/mL BSA, 100 uM Na3VO4 and 0.5 mM DTT. HTRF Detection Buffer:HTRF detection buffer contains 100 mM HEPES-pH 7.5, 100 mM NaCl, 0.1% BSA, 0.05% Tween-20, and 10 mM EDTA. Serial Dilution of Compounds: Compounds were dissolved in 100% DMSO and serially diluted (3 fold, 10 point) in a polypropylene 96-well microtiter plate (drug plate). The final starting concentration of compounds in the p38alpha enzymatic assays was 1 uM. Columns 6 and 12 (HI controls and LO controls respectively) in the drug plate were reserved as controls and contained only DMSO.Kinase Reaction: The p38alpha kinase reactions were carried out in a polypropylene 96-well black round bottom assay plate in total volume of 30 uL kinase reaction buffer.
Measurement: IC50 = 417 nM (pChEMBL 6.380000114440918)
Descriptors: MW 388.4, ALogP 4.34, HBA 5, HBD 1, PSA 90.99, QED 0.56
Compound (SMILES): COc1ccc(N/C(=C/[N+](=O)[O-])NCCCn2cncc2C)c(OC)c1
InChIKey: PCLRPJYQKLMMKX-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 361.4, ALogP 2.38, HBA 8, HBD 2, PSA 103.48, QED 0.38
Compound (SMILES): COc1cc(N/C(=C/[N+](=O)[O-])NCCCn2cncc2C)cc(OC)c1OC
InChIKey: DRBBILLFANXMKL-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 391.43, ALogP 2.38, HBA 9, HBD 2, PSA 112.71, QED 0.34
Compound (SMILES): COc1ccc(N/C(=C/[N+](=O)[O-])NCCCn2cncc2C)cc1OC
InChIKey: XGSCKLKAQKSJDK-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 361.4, ALogP 2.38, HBA 8, HBD 2, PSA 103.48, QED 0.38
Compound (SMILES): Cc1cncn1CCCCN/C(=C\[N+](=O)[O-])NC1CCCCC1
InChIKey: KJDYILRPNDWKLG-FOWTUZBSSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 321.43, ALogP 2.56, HBA 6, HBD 2, PSA 85.02, QED 0.41
Compound (SMILES): Cc1cncn1CCCN/C(=C\[N+](=O)[O-])Nc1ccc2c(c1)OCO2
InChIKey: JUISCZDVYAJMBT-CXUHLZMHSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 345.36, ALogP 2.09, HBA 8, HBD 2, PSA 103.48, QED 0.43
Compound (SMILES): Cc1cn(CCCN/C(=C\[N+](=O)[O-])Nc2ccc(Cl)cc2)cn1
InChIKey: HYOMTYOMNXAQKB-XNTDXEJSSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 335.8, ALogP 3.01, HBA 6, HBD 2, PSA 85.02, QED 0.44
Compound (SMILES): COc1ccc(N/C(=C/[N+](=O)[O-])NCCCn2cnc(C)c2)cc1OC
InChIKey: WEHWOHAOZUUTLE-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 8730 nM (pChEMBL 5.059999942779541)
Descriptors: MW 361.4, ALogP 2.38, HBA 8, HBD 2, PSA 103.48, QED 0.38
Compound (SMILES): COc1cc(N/C(=C/[N+](=O)[O-])NCCCn2cnc(C)c2)cc(OC)c1OC
InChIKey: QXWLNJOMXZMNTB-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 9680 nM (pChEMBL 5.010000228881836)
Descriptors: MW 391.43, ALogP 2.38, HBA 9, HBD 2, PSA 112.71, QED 0.34
Compound (SMILES): COc1ccc(N/C(=C/[N+](=O)[O-])NCCCn2cnc(C)c2)c(OC)c1
InChIKey: HJEWLERUZOGYCA-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 9450 nM (pChEMBL 5.03000020980835)
Descriptors: MW 361.4, ALogP 2.38, HBA 8, HBD 2, PSA 103.48, QED 0.38
Compound (SMILES): Cc1cn(CCCN/C(=C\[N+](=O)[O-])Nc2ccc3c(c2)OCO3)cn1
InChIKey: DRDRFTRZLLMRCL-CXUHLZMHSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 10400 nM (pChEMBL 4.980000019073486)
Descriptors: MW 345.36, ALogP 2.09, HBA 8, HBD 2, PSA 103.48, QED 0.43
Compound (SMILES): Cc1cn(CCCN/C(=C\[N+](=O)[O-])Nc2cccc3ccccc23)cn1
InChIKey: GZQGQPXNGNLMNL-CPNJWEJPSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 7460 nM (pChEMBL 5.130000114440918)
Descriptors: MW 351.41, ALogP 3.51, HBA 6, HBD 2, PSA 85.02, QED 0.37
Compound (SMILES): Cc1cn(CCCN/C(C[N+](=O)[O-])=N/c2ccc3c(c2)OCCO3)cn1
InChIKey: KJIVXLFFKWSWIW-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 8790 nM (pChEMBL 5.059999942779541)
Descriptors: MW 359.39, ALogP 1.95, HBA 7, HBD 1, PSA 103.81, QED 0.27
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])NC1CCCCC1
InChIKey: YAPJFJYUXSGRHO-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 307.4, ALogP 2.18, HBA 5, HBD 1, PSA 85.35, QED 0.27
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1ccc(Cl)cc1
InChIKey: OVKWACFPXWSZFC-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 335.8, ALogP 3.02, HBA 5, HBD 1, PSA 85.35, QED 0.28
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1ccc(C(F)(F)F)cc1
InChIKey: GPQHOIQTHKOAGY-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 369.35, ALogP 3.39, HBA 5, HBD 1, PSA 85.35, QED 0.27
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1cccc2ccccc12
InChIKey: AMQXTNLKQTXNJU-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 351.41, ALogP 3.52, HBA 5, HBD 1, PSA 85.35, QED 0.23
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1ccc2c(c1)OCCO2
InChIKey: MZYLSVFGZFWYEJ-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 359.39, ALogP 2.14, HBA 7, HBD 1, PSA 103.81, QED 0.27
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1cn2ccccc2n1
InChIKey: RZHIROLSHLFRRS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 86.6 nM (pChEMBL 7.059999942779541)
Descriptors: MW 352.4, ALogP 0.89, HBA 6, HBD 1, PSA 84.53, QED 0.74
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc2ccccc2n1C
InChIKey: RDRUHVXSVRSDJK-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 366.43, ALogP 1.13, HBA 6, HBD 1, PSA 85.05, QED 0.73
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc(-c2ccccc2)no1
InChIKey: JBNVUPZXIUSIFD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 380.41, ALogP 1.29, HBA 7, HBD 1, PSA 106.15, QED 0.69
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc(-c2cccnc2)n[nH]1
InChIKey: JDKJKCDNSKZJDD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 380.41, ALogP 0.42, HBA 7, HBD 2, PSA 121.69, QED 0.64
Compound (SMILES): Cc1cccn2cc(CCNC(=O)c3c(C(=O)N4CCC4)cnn3C)nc12
InChIKey: NSEYRCCDASJGOP-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 417.7 nM (pChEMBL 6.380000114440918)
Descriptors: MW 366.43, ALogP 1.19, HBA 6, HBD 1, PSA 84.53, QED 0.74
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc(-c2ccc(Cl)cc2)no1
InChIKey: AFQLNMAETZMENR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 399.9 nM (pChEMBL 6.400000095367432)
Descriptors: MW 414.85, ALogP 1.94, HBA 7, HBD 1, PSA 106.15, QED 0.66
Compound (SMILES): Cn1cc(-c2ccccc2)nc1CCNC(=O)c1c(C(=O)N2CCC2)cnn1C
InChIKey: PPQVWRNRKSICPC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 392.46, ALogP 1.64, HBA 6, HBD 1, PSA 85.05, QED 0.69
Compound (SMILES): Cc1nc(C(=O)N2CCOCC2)c(C(=O)NCCc2nc3ccccc3n2C)n1C
InChIKey: FBZZTAQIQRPQIU-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 1085.4 nM (pChEMBL 5.960000038146973)
Descriptors: MW 410.48, ALogP 1.06, HBA 7, HBD 1, PSA 94.28, QED 0.68
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc2ccccc2s1
InChIKey: VMGMXJGJSYTSCA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 189.4 nM (pChEMBL 6.71999979019165)
Descriptors: MW 369.45, ALogP 1.85, HBA 6, HBD 1, PSA 80.12, QED 0.74
Compound (SMILES): Cn1cnc(C(=O)N2CCC2)c1C(=O)NCCc1nc2ccccc2n1C
InChIKey: NYAIYQIOXQNCIM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 2251.3 nM (pChEMBL 5.650000095367432)
Descriptors: MW 366.43, ALogP 1.13, HBA 6, HBD 1, PSA 85.05, QED 0.73
Compound (SMILES): Cc1ccc2c(c1)nc(CCNC(=O)c1c(C(=O)N3CCC3)cnn1C)n2C
InChIKey: HUTBBLNYUSOTNN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 380.45, ALogP 1.43, HBA 6, HBD 1, PSA 85.05, QED 0.73
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCn1ccc(-c2ccccc2)n1
InChIKey: ZSLQULNTCKVERZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 378.44, ALogP 1.56, HBA 6, HBD 1, PSA 85.05, QED 0.71
Compound (SMILES): Cn1c(Cl)nc(C(=O)N2CCC2)c1C(=O)NCCc1nc2ccccc2n1C
InChIKey: JCSSSICHZLJDBM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 658.7 nM (pChEMBL 6.179999828338623)
Descriptors: MW 400.87, ALogP 1.78, HBA 6, HBD 1, PSA 85.05, QED 0.71
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc(-c2ccncc2)n[nH]1
InChIKey: QQHIJVCYUAPNDD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 714.3 nM (pChEMBL 6.150000095367432)
Descriptors: MW 380.41, ALogP 0.42, HBA 7, HBD 2, PSA 121.69, QED 0.64
Compound (SMILES): Cn1nc(-c2cccnc2)nc1CCNC(=O)c1c(C(=O)N2CCC2)cnn1C
InChIKey: FGKGRFUSWDDSPS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 207.2 nM (pChEMBL 6.679999828338623)
Descriptors: MW 394.44, ALogP 0.43, HBA 8, HBD 1, PSA 110.83, QED 0.65
Compound (SMILES): Cn1ncc(C(=O)N2CCC2)c1C(=O)NCCc1nc2cc(Cl)ccc2n1C
InChIKey: KTJSWFOUCQJZPW-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707).The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 ul contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme.
Measurement: IC50 = 20.5 nM (pChEMBL 7.690000057220459)
Descriptors: MW 400.87, ALogP 1.78, HBA 6, HBD 1, PSA 85.05, QED 0.71