lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCN(Cc2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4CC(N)=O)n3)cc2)CC1
InChIKey: ACIBTFUWZHGTPF-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Phospho ELISA Assay: Adult human dermal lymphatic microvascular endothelial cells (HMVEC-dLyAD) (Cat# CC-2810, Lonza) were seeded into clear-bottom, TC treated 12 well plates (Cat #665180, Greiner Bio-One) in Endogro MV complete (Cat#SCME004, Millipore) at 200,000 cells/well (volume 1 mL), and the plates incubated at 37 C. and 5% CO2 for 6 hours. The media was replaced with Endogro Basal (Cat # SCME-BM, Millipore)+0.1% BSA (Cat# A8412, Sigma) and cells incubated for a further period (overnight at 37 C. and 5% CO2).96 well Maxisorp immuno plates (Cat #439454, Nunc) were coated with 100 uL of Total VEGFR2 capture antibody (Part #841888, Human Total VEGFR3/Flt4 ELISA Kit, Cat # DYC3491, R&D Systems), or Phospho VEGF R3Capture antibody (Part #841885, Human Phospho VEGF R3/Flt4 ELISA Kit, Cat# DYC2724, R&D Systems). The plates were covered and incubated at room temperature overnight. The coating antibody was flicked out and the plates washed three times with Wash Buffer.
Measurement: IC50 = 169 nM (pChEMBL 6.769999980926514)
Descriptors: MW 512.58, ALogP 3.8, HBA 6, HBD 2, PSA 87.38, QED 0.45
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](C=CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CCO1
InChIKey: NNEWMMFHUDIZPO-XUDSTZEESA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 310.44, ALogP 4.23, HBA 2, HBD 0, PSA 26.3, QED 0.63
Compound (SMILES): C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(C)[C@@H](CC[C@@]34C=CCO4)[C@@H]21
InChIKey: QLCLQHCJXWSVTF-JGUZPDMNSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 326.48, ALogP 4.7, HBA 2, HBD 0, PSA 26.3, QED 0.6
Compound (SMILES): CC[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(C)[C@@H](CC[C@@]34C=CCO4)[C@H]12
InChIKey: USLUSBGRSPWYFF-NLQREHEDSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 340.51, ALogP 5.09, HBA 2, HBD 0, PSA 26.3, QED 0.62
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC1(CC1)[C@@]21C=CCO1
InChIKey: QGNJUOXZTPPCOF-YYGBOFOUSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 338.49, ALogP 4.84, HBA 2, HBD 0, PSA 26.3, QED 0.59
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H]([C@H](C)CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CCO1
InChIKey: FXOBRTHYLJLPSC-NLQREHEDSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 340.51, ALogP 5.09, HBA 2, HBD 0, PSA 26.3, QED 0.62
Compound (SMILES): CC[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(CC)[C@@H](CC[C@@]34C=CCO4)[C@H]12
InChIKey: KSBBSPJEGUHNTP-YCZZPANZSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 354.53, ALogP 5.48, HBA 2, HBD 0, PSA 26.3, QED 0.61
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H](C[C@@H](CO)C4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CCO1
InChIKey: HZRWBHDMULHBAO-PHRMCSLUSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Receptor Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 356.51, ALogP 4.06, HBA 3, HBD 1, PSA 46.53, QED 0.76
Compound (SMILES): CNC(=O)c1c(C(N)=O)nc2n1CCOc1ccc(C#C[C@@](C)(O)c3cc(C)on3)cc1-2
InChIKey: HYLUNVLDXOSFLG-JOCHJYFZSA-N
Target: Transcription factor p65 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04206
Assay: Inhibition of TNF-alpha-stimulated RELA translocation from cytoplasm to nucleus in human HeLa cells preincubated for 4.5 hrs followed by TNF-alpha stimulation measured after 30 mins
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 435.44, ALogP 0.96, HBA 8, HBD 3, PSA 145.5, QED 0.52
Compound (SMILES): CN1CCN(C(=O)c2ccc(-c3noc(C(F)(F)F)n3)cc2)CC1
InChIKey: MNYTWBQGSPDBNG-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using Boc-Lys-(Tfa)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 90 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 16100 nM (pChEMBL 4.789999961853027)
Descriptors: MW 340.31, ALogP 2.14, HBA 5, HBD 0, PSA 62.47, QED 0.84
Compound (SMILES): O=C(NC1CCNC1)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: UHMRHXFYCAGYDK-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition Assay: Human recombinant HDAC4 was expressed in full length form (aa 2-1084) in Sf9 insect cells (obtained from ATCC) using baculovirus generated with Bac-to-Bac system (Invitrogen). Test compounds were serially diluted to reach final test concentrations from 0.000128 uM to 10 uM. HDAC4 and test compounds were incubated in 25 mM Tris buffer pH 8.0 containing 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 0.05% (w/v) bovine serum albumine and 0.005% (v/v) Triton-X-100 for 2 hours at room temperature in presence of 5 uM of acetyl-Gly-Ala-Lys(E-trifluoroacetyl)-AMC (AMC=7-amino-4-methyl coumarin) in a final volume of 9 ul. Control wells with HDAC4 only (positive control) and without HDAC4 (negative control) were included on the microplate. Bovine trypsin (4.5 ul of a 300 nM solution) was added and the plate incubated for additional 15 minutes at room temperature. The plate was placed in a fluorescence microplate reader, and read at an excitation wavelength of 360 nm.
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 326.28, ALogP 1.85, HBA 5, HBD 2, PSA 80.05, QED 0.9
Compound (SMILES): C[C@H](CN1CCCC1)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: GPAXDYNOSUVDDO-LLVKDONJSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin) using Boc Lys(TFA) as substrate by fluorogenic assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 368.36, ALogP 2.97, HBA 5, HBD 1, PSA 71.26, QED 0.88
Compound (SMILES): C[C@H](CN1CCCCC1)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: WTZFUFARAWDPGC-GFCCVEGCSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of Class 2A HDAC4 in human Jurkat E6.1 cells using Boc-Lys-(TFA)-AMC as substrate by fluorogenic assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 382.39, ALogP 3.36, HBA 5, HBD 1, PSA 71.26, QED 0.86
Compound (SMILES): CCCN(CCC)C[C@@H](C)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: HMXFCVJIASWKMB-CYBMUJFWSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin) using Boc Lys(TFA) as substrate by fluorogenic assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 398.43, ALogP 4, HBA 5, HBD 1, PSA 71.26, QED 0.69
Compound (SMILES): CCN(CC)CCNC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: PZAVITOFPPUOOH-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 4020 nM (pChEMBL 5.400000095367432)
Descriptors: MW 356.35, ALogP 2.83, HBA 5, HBD 1, PSA 71.26, QED 0.83
Compound (SMILES): C[C@H](CN(C)Cc1ccccc1)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: RESDVUQVZOJNSO-CQSZACIVSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human HDAC9 using fluorogenic substrate by fluorescence microplate reader assay
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 418.42, ALogP 4.01, HBA 5, HBD 1, PSA 71.26, QED 0.63
Compound (SMILES): Cc1c(CCN2CCN(C(=O)Cc3ccc(-n4cnnn4)nc3)CC2)ccc2c1COC2=O
InChIKey: PDBQDSXSCZPLNA-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology analysis
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 447.5, ALogP 0.97, HBA 9, HBD 0, PSA 106.34, QED 0.51
Compound (SMILES): C[C@H](O)CNS(=O)(=O)c1ccccc1-c1ccc(-c2cnc(N)nc2)c(F)c1
InChIKey: WVRMEAAIRKEPMP-LBPRGKRZSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 402.45, ALogP 2.19, HBA 6, HBD 3, PSA 118.2, QED 0.58
Compound (SMILES): C[C@@H](CO)NS(=O)(=O)c1ccccc1-c1ccc(-c2ccc(N)nc2)c(F)c1
InChIKey: UIRUYUXLIJYMMM-ZDUSSCGKSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 401.46, ALogP 2.8, HBA 5, HBD 3, PSA 105.31, QED 0.59
Compound (SMILES): CC#Cc1cncc(-c2ccc(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)c1
InChIKey: PYKIYRAPQBZWOP-XAUMDUMWSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Fluorescence Resonance Energy Transfer Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 91600 nM (pChEMBL 4.039999961853027)
Descriptors: MW 371.36, ALogP 3.45, HBA 4, HBD 1, PSA 60.5, QED 0.84
Compound (SMILES): COc1cnc(C(=O)Nc2ccc(F)c([C@]3(C)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: LUOFRFUNXXGHFC-FVMIAERFSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Fluorescence Resonance Energy Transfer Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 42800 nM (pChEMBL 4.369999885559082)
Descriptors: MW 371.37, ALogP 1.83, HBA 7, HBD 2, PSA 111.72, QED 0.85
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(O)ccc3Cl)nnc12
InChIKey: OOMWWAGKPLNKNM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 311.73, ALogP 3.01, HBA 6, HBD 1, PSA 76.2, QED 0.58
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(O)ccc4Cl)n3c2n1
InChIKey: WREDJOGPAYNGKD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 325.76, ALogP 3.32, HBA 6, HBD 1, PSA 76.2, QED 0.58
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(O)ccc3F)nnc12
InChIKey: GWNXVUOBUDPUMJ-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 295.28, ALogP 2.49, HBA 6, HBD 1, PSA 76.2, QED 0.58
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OCCCO)ccc3Cl)nnc12
InChIKey: RZEAWYYGBJVDMD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 2190 nM (pChEMBL 5.659999847412109)
Descriptors: MW 369.81, ALogP 3.06, HBA 7, HBD 1, PSA 85.43, QED 0.54
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OCCO)ccc3Cl)nnc12
InChIKey: MNZFNMJZWDCKKG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 355.79, ALogP 2.67, HBA 7, HBD 1, PSA 85.43, QED 0.61
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OCC(C)O)ccc3Cl)nnc12
InChIKey: VOEFMCIEHPUNPS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 1876 nM (pChEMBL 5.730000019073486)
Descriptors: MW 369.81, ALogP 3.06, HBA 7, HBD 1, PSA 85.43, QED 0.59
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OC[C@@H](C)O)ccc3Cl)nnc12
InChIKey: VOEFMCIEHPUNPS-SNVBAGLBSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 5720 nM (pChEMBL 5.239999771118164)
Descriptors: MW 369.81, ALogP 3.06, HBA 7, HBD 1, PSA 85.43, QED 0.59
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OC[C@H](C)O)ccc3Cl)nnc12
InChIKey: VOEFMCIEHPUNPS-JTQLQIEISA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 3010 nM (pChEMBL 5.519999980926514)
Descriptors: MW 369.81, ALogP 3.06, HBA 7, HBD 1, PSA 85.43, QED 0.59
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OC4CCOCC4)ccc3Cl)nnc12
InChIKey: OADAUDWHZOSPMI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 8162 nM (pChEMBL 5.090000152587891)
Descriptors: MW 395.85, ALogP 3.86, HBA 7, HBD 0, PSA 74.43, QED 0.52
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OC4CCC(F)(F)CC4)ccc3Cl)nnc12
InChIKey: NLLOXUYIVDWUMQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 2820 nM (pChEMBL 5.550000190734863)
Descriptors: MW 429.86, ALogP 5.26, HBA 6, HBD 0, PSA 65.2, QED 0.44
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OC4CCOC4)ccc3Cl)nnc12
InChIKey: RBIPQUPPQHENAE-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Radioactive Assay: For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount with a recording time of 3 min/well.PDE 2A protein is expressed upon baculovirus infection in SF9 cells. The cells have been incubated upon infection for 3 days and protein production was confirmed.
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 381.82, ALogP 3.47, HBA 7, HBD 0, PSA 74.43, QED 0.54
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OCC4CCOC4)ccc3Cl)nnc12
InChIKey: AZQAPZPQRNXTJY-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 395.85, ALogP 3.72, HBA 7, HBD 0, PSA 74.43, QED 0.52
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OCCCO)ccc4Cl)n3c2n1
InChIKey: MYTWOYABQDJPSU-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 383.84, ALogP 3.37, HBA 7, HBD 1, PSA 85.43, QED 0.53
Compound (SMILES): COCCOc1ccc(Cl)c(-c2nnc3c(C)nc4ccc(C)nc4n23)c1
InChIKey: YTXVHBVKSXOZAK-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 2380 nM (pChEMBL 5.619999885559082)
Descriptors: MW 383.84, ALogP 3.63, HBA 7, HBD 0, PSA 74.43, QED 0.49
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OC5CCC(F)(F)CC5)ccc4Cl)n3c2n1
InChIKey: WTZCQCTWMAHHPH-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 3920 nM (pChEMBL 5.409999847412109)
Descriptors: MW 443.89, ALogP 5.57, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COCCCOc1ccc(Cl)c(-c2nnc3c(C)nc4ccc(C)nc4n23)c1
InChIKey: XXOXYYIHSNWLAR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 397.87, ALogP 4.03, HBA 7, HBD 0, PSA 74.43, QED 0.46
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OC5CCOCC5)ccc4Cl)n3c2n1
InChIKey: SZDKYLLVLPNRMF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 1760 nM (pChEMBL 5.75)
Descriptors: MW 409.88, ALogP 4.17, HBA 7, HBD 0, PSA 74.43, QED 0.51
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OCCCOC(F)(F)F)ccc4Cl)n3c2n1
InChIKey: LCIONKYVFWJFMY-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 451.84, ALogP 4.92, HBA 7, HBD 0, PSA 74.43, QED 0.39
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OC[C@H](C)O)ccc4Cl)n3c2n1
InChIKey: IQKUDFYGJLMDTB-NSHDSACASA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 1890 nM (pChEMBL 5.71999979019165)
Descriptors: MW 383.84, ALogP 3.37, HBA 7, HBD 1, PSA 85.43, QED 0.58
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OC[C@@H](C)O)ccc4Cl)n3c2n1
InChIKey: IQKUDFYGJLMDTB-LLVKDONJSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Radioactive Assay: For assessing activity of compounds on PDE10 inhibition, the following modifications of the protocol described below are applied:  protein amount: 3 ng  protein concentration: 75 ug/ul.For all experiments the Phosphodiesterase [3H]cAMP SPA Enzyme Assay (TRKQ7090, GE Healthcare Europe GmbH) were used. The enzymatic activity of the PDE2 and the inhibitory potency of compounds was measured by the conversion of [3H]cAMP to [3H]AMP. [3H]AMP associate to the scintillator soaked yttrium-silicate beads resulting in an increase in scintillation events. Compounds that inhibit the respective enzymes decrease the generation of [3H]AMP and accordingly the number of counts detected.SF9 lysate containing PDE2A is incubated at room temperature for 1 h with [3H]cAMP and the reaction is terminated by addition of SPA beads in 18 mM zinc sulphate. The [3H]AMP bound to SPA beads is determined after at least 3 hours of sedimentation of the beads, the signal is recorded using the TopCount.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 383.84, ALogP 3.37, HBA 7, HBD 1, PSA 85.43, QED 0.58
Compound (SMILES): Cc1nc2cccnc2n2c(-c3cc(OC4CCC(O)C4)ccc3Cl)nnc12
InChIKey: IOLGYGMKMVZBTC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 8707 nM (pChEMBL 5.059999942779541)
Descriptors: MW 395.85, ALogP 3.59, HBA 7, HBD 1, PSA 85.43, QED 0.57
Compound (SMILES): Cc1ccc2nc(C)c3nnc(-c4cc(OC5CCOC5)ccc4Cl)n3c2n1
InChIKey: IPHFTQNPLVTVML-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Fluorescence Polarization Assay: The inhibition of PDE 2A or 10 enzyme activity was assessed using IMAP-Phosphodiesterase-cAMP fluorescence labeled substrate (Molecular Devices, Order No. R7506), IMAP TR-FRET screening express (Molecular Devices, Order No. R8160, the TR-FRET component will not be used) and PDE 2A or PDE10 protein expressed upon baculovirus infection in SF9 cells. The cells were incubated after infection for ~3 days and protein production was confirmed by Western Blot. The cells were collected by centrifugation and the pellet frozen in liquid nitrogen before it was resuspended in PBS containing 1% Triton X-100 and protease inhibitors. After 45 min incubation on ice, the cell debris was removed by centrifugation (13.000 rpm, 30 min). Since SF 9 cells do not express cAMP hydrolyzing enzymes to a high extent, no further purification of the protein was needed.All reactions were performed in 384 well plates, Perkin Elmer black optiplates and IMAP reaction buffer with 0.1% Tween20 (kit component).
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 395.85, ALogP 3.78, HBA 7, HBD 0, PSA 74.43, QED 0.53