lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1Oc1ccccn1
InChIKey: ROWCDUKNAFYOMJ-VEAWDGRHSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.03 nM (pChEMBL 10.520000457763672)
Descriptors: MW 533.55, ALogP 5.5, HBA 6, HBD 2, PSA 103.02, QED 0.34
Compound (SMILES): COCCOc1cc(F)c(-c2nc(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@H](OC)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: CKRMSGUCWWVREC-GZDINDOJSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 544.57, ALogP 4.69, HBA 7, HBD 2, PSA 108.59, QED 0.38
Compound (SMILES): CCOCc1cc(F)c(-c2nc(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@@H](OCCS(C)(=O)=O)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: LPJZLEGMOKXVFB-HEBSFQMOSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.79 nM (pChEMBL 8.75)
Descriptors: MW 620.69, ALogP 4.62, HBA 8, HBD 2, PSA 133.5, QED 0.32
Compound (SMILES): CO[C@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2nc(-c3cc(C(=O)NC(C)C)ccc3F)ccc2N)C[C@@H]1C
InChIKey: JAVVLMYHUYZZDN-JCCCCHRMSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 2.56 nM (pChEMBL 8.59000015258789)
Descriptors: MW 534.64, ALogP 4.11, HBA 7, HBD 4, PSA 145.25, QED 0.36
Compound (SMILES): CO[C@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(C4(F)CCOCC4)cc3F)n2)C[C@@H]1C
InChIKey: ZCTSKEOHMXXIST-XCPDJCNPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.98 nM (pChEMBL 8.699999809265137)
Descriptors: MW 572.6, ALogP 5.64, HBA 6, HBD 2, PSA 99.36, QED 0.37
Compound (SMILES): CC(C)NC(=O)c1ccc(F)c(-c2ccc(N)c(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@@H](OCCS(C)(=O)=O)[C@@H](C)C3)n2)c1
InChIKey: WUOXBBAOJFCZKX-BEXDQNPLSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.21 nM (pChEMBL 8.920000076293945)
Descriptors: MW 626.76, ALogP 3.53, HBA 9, HBD 4, PSA 179.39, QED 0.26
Compound (SMILES): COc1cc(C(F)(F)F)ccc1-c1ncnc2cc(S(=O)(=O)Nc3nccs3)ccc12
InChIKey: VSUDRCZPHWUXEW-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: In Vitro PX Assay: 293 cells stably transfected with Nav 1.5 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system according the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, Calif.). Cells were held at a holding potential of −50 mV to inactivate sodium channels. To elicit sodium currents the voltage was changed to −120 mV to recover a portion of the channels, followed by delivery of test pulses of 20 msec duration to 0 mV, at 0.1 Hz. A single concentration of test compound was applied to cells for a duration of 5 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 466.47, ALogP 4.58, HBA 7, HBD 1, PSA 94.07, QED 0.46
Compound (SMILES): COc1cc(C(F)(F)F)ccc1-c1ccnc2cc(S(=O)(=O)Nc3nccs3)ccc12
InChIKey: OEXUGFJXGSYFJL-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: In Vitro PX Assay: 293 cells stably transfected with Nav 1.5 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system according the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, Calif.). Cells were held at a holding potential of −50 mV to inactivate sodium channels. To elicit sodium currents the voltage was changed to −120 mV to recover a portion of the channels, followed by delivery of test pulses of 20 msec duration to 0 mV, at 0.1 Hz. A single concentration of test compound was applied to cells for a duration of 5 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 465.48, ALogP 5.19, HBA 6, HBD 1, PSA 81.18, QED 0.44
Compound (SMILES): COc1cc(-c2cccc(F)c2)ccc1-c1ncnc2cc(S(=O)(=O)Nc3ccncn3)ccc12
InChIKey: UCTIWUWTSINRLP-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: In Vitro PX Assay: 293 cells stably transfected with Nav 1.5 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system according the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, Calif.). Cells were held at a holding potential of −50 mV to inactivate sodium channels. To elicit sodium currents the voltage was changed to −120 mV to recover a portion of the channels, followed by delivery of test pulses of 20 msec duration to 0 mV, at 0.1 Hz. A single concentration of test compound was applied to cells for a duration of 5 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 487.52, ALogP 4.7, HBA 7, HBD 1, PSA 106.96, QED 0.37
Compound (SMILES): COc1cc(-c2cccc(F)c2)c(Cl)cc1-c1nccc2cc(S(=O)(=O)Nc3ncns3)ccc12
InChIKey: BXXHSWZOLFWSPZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 527, ALogP 6.02, HBA 7, HBD 1, PSA 94.07, QED 0.29
Compound (SMILES): COc1cc(-c2cccc(F)c2)c(Cl)cc1-c1nccc2cc(S(=O)(=O)Nc3ccncn3)ccc12
InChIKey: CUAWFKPONCJPMJ-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells assessed as reduction in peak inward current by ionworks quattro electrophysiology assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 520.97, ALogP 5.96, HBA 6, HBD 1, PSA 94.07, QED 0.3
Compound (SMILES): COc1cc(-c2cccc(F)c2)c(Cl)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12
InChIKey: PLEDPBLRULDFLA-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells assessed as reduction in peak inward current by ionworks quattro electrophysiology assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.95, ALogP 6.16, HBA 6, HBD 1, PSA 94.32, QED 0.29
Compound (SMILES): COc1ccc(C(=O)N[C@@H](CC(=O)O)c2ccccc2Cl)nc1-c1cccnc1
InChIKey: RENWHBZDKJUWMV-KRWDZBQOSA-N
Target: Lysosomal protective protein (SINGLE PROTEIN), Homo sapiens
UniProt: P10619
Assay: Inhibition Assay: The activated cathepsin A was diluted in assay buffer (25 mM MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound (dissolved in assay buffer containing (v/v) 3% DMSO) or, in the control experiments, with the vehicle in a multiple assay plate. After incubation for 15 min at room temperature, as substrate then bradykinin carrying an N-terminal ®Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) label (JPT Peptide Technologies GmbH; dissolved in assay buffer) was added to the mixture. The final concentration of cathepsin A was 833 ng/ml and the final concentration of labeled bradykinin 2 μM. After incubation for 15 min at room temperature the reaction was stopped by the addition of stop buffer (130 mM 2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4, containing (v/v) 0.013% ®Triton X-100, 0.13% Coating Reagent 3 (Caliper Life Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, #E0886)).
Measurement: IC50 = 7540 nM (pChEMBL 5.119999885559082)
Descriptors: MW 411.85, ALogP 3.75, HBA 5, HBD 2, PSA 101.41, QED 0.61
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CCO1
InChIKey: VXKBREQCYRAEHY-XUDSTZEESA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
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 mineralocorticoid receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-aldosterone.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 312.45, ALogP 4.45, HBA 2, HBD 0, PSA 26.3, QED 0.62
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C(F)(F)F)c1c2=O
InChIKey: OICPOZZKXXBDTD-CYBMUJFWSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of QPP (unknown origin) preincubated for 30 mins followed by Nle-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 479.44, ALogP 1.7, HBA 8, HBD 1, PSA 102.28, QED 0.57
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3ccccc3C#N)c1c2=O
InChIKey: PNGZLJFKFMSBJO-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin) preincubated for 20 mins followed by Gly-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 418.46, ALogP 0.42, HBA 9, HBD 1, PSA 126.07, QED 0.65
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3F)c1c2=O
InChIKey: YAWOUZPWJKYFDX-CYBMUJFWSA-N
Target: Dipeptidyl peptidase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6V1X1
Assay: Inhibition of recombinant DPP8 (unknown origin) preincubated for 20 mins followed by Ala-Pro-AFC addition measured for 40 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 429.43, ALogP 0.82, HBA 8, HBD 1, PSA 102.28, QED 0.66
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2nc3n(c(=O)c21)CC(=O)N3C
InChIKey: PPMZXTYNICRHMC-LLVKDONJSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of QPP (unknown origin) preincubated for 30 mins followed by Nle-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 355.4, ALogP -0.48, HBA 8, HBD 1, PSA 102.28, QED 0.73
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3F)c1c2=O
InChIKey: ULGAIQGMBBLSSH-CQSZACIVSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of QPP (unknown origin) preincubated for 30 mins followed by Nle-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 443.46, ALogP 1.21, HBA 8, HBD 1, PSA 102.28, QED 0.65
Compound (SMILES): CCN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C(F)(F)F)c1c2=O
InChIKey: NHQURNPIJLKKLF-CQSZACIVSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of QPP (unknown origin) preincubated for 30 mins followed by Nle-Pro-AMC addition measured for 50 mins by continuous fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 493.47, ALogP 2.09, HBA 8, HBD 1, PSA 102.28, QED 0.56
Compound (SMILES): CN1C(=O)Cn2c1nc1nc(N3CCC[C@@H](N)C3)n(Cc3cc(F)ccc3C#N)c1c2=O
InChIKey: KMOYVYIQCXEQDG-OAHLLOKOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]MK499 from human ERG
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 436.45, ALogP 0.56, HBA 9, HBD 1, PSA 126.07, QED 0.64
Compound (SMILES): CN(C)C(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: HPOCHXQWZPPNBY-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 285.23, ALogP 2.46, HBA 4, HBD 0, PSA 59.23, QED 0.85
Compound (SMILES): CNC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: OUMSNRPZKWUWES-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 271.2, ALogP 2.12, HBA 4, HBD 1, PSA 68.02, QED 0.91
Compound (SMILES): CNC(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: HDIGXHQTAVNCES-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 285.23, ALogP 2.04, HBA 4, HBD 1, PSA 68.02, QED 0.94
Compound (SMILES): CN(C)C(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: DOZQOPCRFHELFA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 299.25, ALogP 2.39, HBA 4, HBD 0, PSA 59.23, QED 0.87
Compound (SMILES): CC(C)NC(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: MLBIBJOCXAUCPH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 313.28, ALogP 2.82, HBA 4, HBD 1, PSA 68.02, QED 0.94
Compound (SMILES): CCCCNC(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: FGWWMUDKFJLEEP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 327.31, ALogP 3.21, HBA 4, HBD 1, PSA 68.02, QED 0.83
Compound (SMILES): COCCNC(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: OLHZABUSLVLNQH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 329.28, ALogP 2.06, HBA 5, HBD 1, PSA 77.25, QED 0.82
Compound (SMILES): CCOC(=O)CNC(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: ONDBNZKXBIECQO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 357.29, ALogP 1.98, HBA 6, HBD 1, PSA 94.32, QED 0.79
Compound (SMILES): O=C(Cc1ccc(-c2noc(C(F)(F)F)n2)cc1)N1CCOCC1
InChIKey: CFKSFKXROKZYDV-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 341.29, ALogP 2.16, HBA 5, HBD 0, PSA 68.46, QED 0.86
Compound (SMILES): CN1CCN(C(=O)Cc2ccc(-c3noc(C(F)(F)F)n3)cc2)CC1
InChIKey: FHPYVAJINGPABL-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 354.33, ALogP 2.07, HBA 5, HBD 0, PSA 62.47, QED 0.84
Compound (SMILES): CON(C)C(=O)Cc1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: RHOWMWOUFAJXKQ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 315.25, ALogP 2.32, HBA 5, HBD 0, PSA 68.46, QED 0.81
Compound (SMILES): CCNC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: WWCPMLUISCRKPF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 285.23, ALogP 2.51, HBA 4, HBD 1, PSA 68.02, QED 0.94
Compound (SMILES): O=C(NCCO)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: NCMUYLGLYZSHBA-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 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 301.22, ALogP 1.48, HBA 5, HBD 2, PSA 88.25, QED 0.89
Compound (SMILES): CCN(C)C(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: OWYUDNFHZRLOQM-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 299.25, ALogP 2.85, HBA 4, HBD 0, PSA 59.23, QED 0.87
Compound (SMILES): CN(CCO)C(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: DUONAKZCSCVNFH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 315.25, ALogP 1.82, HBA 5, HBD 1, PSA 79.46, QED 0.93
Compound (SMILES): COCCNC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: GUJZIRUOIWKNCQ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 315.25, ALogP 2.13, HBA 5, HBD 1, PSA 77.25, QED 0.86
Compound (SMILES): COCCN(C)C(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: FZARNFAFIAPTIY-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 329.28, ALogP 2.47, HBA 5, HBD 0, PSA 68.46, QED 0.84
Compound (SMILES): CC(C)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: YGJGXPWYQMDHLZ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 299.25, ALogP 2.89, HBA 4, HBD 1, PSA 68.02, QED 0.95
Compound (SMILES): COCCCNC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: HDUDAIBDRVYJPA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 329.28, ALogP 2.52, HBA 5, HBD 1, PSA 77.25, QED 0.82
Compound (SMILES): O=C(NCCF)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: QODBUGGODSSXSA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 303.21, ALogP 2.45, HBA 4, HBD 1, PSA 68.02, QED 0.88
Compound (SMILES): O=C(c1ccc(-c2noc(C(F)(F)F)n2)cc1)N1CCCC1
InChIKey: LDCGWTBLKGMXOU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 311.26, ALogP 2.99, HBA 4, HBD 0, PSA 59.23, QED 0.86
Compound (SMILES): CC(C)N(C)C(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: OBPARYKTAQRTGU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 313.28, ALogP 3.24, HBA 4, HBD 0, PSA 59.23, QED 0.87
Compound (SMILES): O=C(NC1CCC1)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: RCIALLJWGLHRGI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: A similar assay procedure as described in Test 2 was used for HDAC6. Human recombinant full length HDAC6 expressed in a baculovirus expression system was purchased from BPS BioSciences (San Diego, Calif., U.S.A.). The substrate used in the HDAC1 assay was 5 uM of acetyl-Gly-Ala-Lys(acetyl)-AMC. TEST 2: 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).
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 311.26, ALogP 3.04, HBA 4, HBD 1, PSA 68.02, QED 0.95