lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(F)c(O)c4F)c3c2)ccc1O
InChIKey: SUBDZIRWBNUWKU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 395.37, ALogP 4.74, HBA 6, HBD 3, PSA 87.5, QED 0.46
Compound (SMILES): Oc1c(F)ccc(Nc2ncnc3ccc(-c4ccc5[nH]ncc5c4)cc23)c1F
InChIKey: XEVJFJCQCIMXTL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 389.37, ALogP 4.9, HBA 5, HBD 3, PSA 86.72, QED 0.41
Compound (SMILES): Oc1c(F)ccc(Nc2ncnc3ccc(-c4ccc(Cl)cc4)cc23)c1F
InChIKey: MBPYRSULCBJQEY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 383.79, ALogP 5.68, HBA 4, HBD 2, PSA 58.04, QED 0.48
Compound (SMILES): Cc1nc(C)c(CNc2nc(OC[C@H]3C[C@@H]3c3ccccn3)nc(Cl)c2C)s1
InChIKey: MAFLAYQHEPPOKU-CABCVRRESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 415.95, ALogP 4.7, HBA 7, HBD 1, PSA 72.82, QED 0.56
Compound (SMILES): Cc1c(Cl)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1NCc1cnn(C)c1
InChIKey: KIYBJKHIYOZLEC-CABCVRRESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 384.87, ALogP 3.36, HBA 7, HBD 1, PSA 77.75, QED 0.63
Compound (SMILES): CSc1nn(-c2ccccc2C)c2cc(C3=CCNCC3)ccc12
InChIKey: CXRDFIBCRNVOFH-UHFFFAOYSA-N
Target: Ketohexokinase (SINGLE PROTEIN), Homo sapiens
UniProt: P50053
Assay: Enzyme Assay: An enzymatic assay was developed to measure KHK-mediated conversion of D-fructose to Fructose-1-P (F-1-P) using High Throughput Mass Spectroscopy (HTMS) as a means of product detection. This assay served as a primary screen to evaluate the ability to inhibit KHK enzyme activity and it has been adapted to high throughput mass spectrometry (HTMS, BioTrove RapidFire) format for higher throughput.The compounds to be tested were dosed in 12-points concentration from 511 μM to 0.5 μM. Inhibition of the fragment, IC50, was determined in a dose-response curve under the established steady-state conditions of 200 M fructose, 100 μM ATP and 2 nM KHK for 60 min at 25° C. The assay was carried out in 384-well plate format.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 335.48, ALogP 4.43, HBA 4, HBD 1, PSA 29.85, QED 0.72
Compound (SMILES): CC(C)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cc3)c2)c2cnc(N)nc21
InChIKey: ZJGWNGRVSUFGBL-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 448.91, ALogP 4.06, HBA 7, HBD 2, PSA 115.79, QED 0.43
Compound (SMILES): CC(C)n1cc(C(=O)c2cncc(NC(=O)Cn3ccc(C4CC4)n3)c2)c2cnc(N)nc21
InChIKey: YCLNSIOZHCMOPZ-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 444.5, ALogP 2.93, HBA 9, HBD 2, PSA 133.61, QED 0.42
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(n3)-c3c(c(C(N)=O)nn3C)CCC4)cc2)CC1
InChIKey: ACMMEMWMPLSEFY-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Kinase Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds were determined using a trans-phosphorylation assay.Specific peptide or protein substrates are trans-phosphorylated by their specific ser-thr or tyr kinase in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors.At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP is captured by an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity.Supernatant is subsequently withdrawn and transferred into a counting plate, then evaluated by P-counting.Reagents/Assay Conditionsi. Dowex Resin Preparation500 g of wet resin (SIGMA, custom prepared resin DOWEX 1x8 200-400 mesh, 2.5 Kg) are weighed out and diluted to 2 L in 150 mM sodium formate, pH 3.00.The resin is allowed to settle down (some hours) and then the supernatant is discarded.
Measurement: IC50 = 1196 nM (pChEMBL 5.920000076293945)
Descriptors: MW 432.53, ALogP 1.96, HBA 8, HBD 2, PSA 105.2, QED 0.65
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc2c(n1)-c1c(c(C(N)=O)nn1C)CCC2
InChIKey: GEMLZQBJYPNJIS-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Kinase Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds were determined using a trans-phosphorylation assay.Specific peptide or protein substrates are trans-phosphorylated by their specific ser-thr or tyr kinase in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors.At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP is captured by an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity.Supernatant is subsequently withdrawn and transferred into a counting plate, then evaluated by P-counting.Reagents/Assay Conditionsi. Dowex Resin Preparation500 g of wet resin (SIGMA, custom prepared resin DOWEX 1x8 200-400 mesh, 2.5 Kg) are weighed out and diluted to 2 L in 150 mM sodium formate, pH 3.00.The resin is allowed to settle down (some hours) and then the supernatant is discarded.
Measurement: IC50 = 194 nM (pChEMBL 6.710000038146973)
Descriptors: MW 462.56, ALogP 1.97, HBA 9, HBD 2, PSA 114.43, QED 0.59
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc2c(n1)-c1c(c(C(=O)N[C@H](CN)c3ccccc3)nn1C)CCC2
InChIKey: NAGOZOOVQLAGAY-HHHXNRCGSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Kinase Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds were determined using a trans-phosphorylation assay.Specific peptide or protein substrates are trans-phosphorylated by their specific ser-thr or tyr kinase in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors.At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP is captured by an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity.Supernatant is subsequently withdrawn and transferred into a counting plate, then evaluated by P-counting.Reagents/Assay Conditionsi. Dowex Resin Preparation500 g of wet resin (SIGMA, custom prepared resin DOWEX 1x8 200-400 mesh, 2.5 Kg) are weighed out and diluted to 2 L in 150 mM sodium formate, pH 3.00.The resin is allowed to settle down (some hours) and then the supernatant is discarded.
Measurement: IC50 = 469 nM (pChEMBL 6.329999923706055)
Descriptors: MW 623.76, ALogP 3.37, HBA 10, HBD 4, PSA 152.32, QED 0.22
Compound (SMILES): O=C(CC1CC1)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3OCO4)CC2)CC1
InChIKey: WTONWMINNVVDTM-XGAFWQRZSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Biochemical Assay: The ability of the compounds to bind to the 5-HT2A, D3 and D2 receptors was determined using radioligand binding to cloned receptors selectively expressed in HEK-293 EBNA cells.
Measurement: Ki = 302.84 nM (pChEMBL 6.519999980926514)
Descriptors: MW 412.57, ALogP 4.46, HBA 4, HBD 1, PSA 50.8, QED 0.72
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(CCCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: AMZWCCRFPBPFAY-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of recombinant 6His-tagged GLS1 KGA isoform (unknown origin) (63 to 669 residues) expressed in Escherichia coli using glutamine as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by amplex red staining-based horseradish peroxidase/glutamate oxidase coupled assay
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 492.63, ALogP 4.32, HBA 8, HBD 2, PSA 109.76, QED 0.3
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(CCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: COSPOTYTNSRZGK-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Allosteric inhibition of human kidney glutaminase using [3H]-Glutamine as substrate in presence of inhibitor incubated for 45 mins by Perkin Elmer based assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 478.6, ALogP 3.93, HBA 8, HBD 2, PSA 109.76, QED 0.36
Compound (SMILES): CCOC(=O)c1ccc(-c2ccc3c(C=O)c(O)ccc3c2)s1
InChIKey: OVMSLXCDVVLIPE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 326.37, ALogP 4.26, HBA 5, HBD 1, PSA 63.6, QED 0.57
Compound (SMILES): O=Cc1c(O)ccc2cc(-c3cccc(C(=O)O)n3)ccc12
InChIKey: XDSPFOAMCKFUPU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 293.28, ALogP 3.12, HBA 4, HBD 2, PSA 87.49, QED 0.72
Compound (SMILES): O=c1[nH]c2ccccc2n(C2CCN(C3CCCCCCC3)CC2)c1=O
InChIKey: NMRCIXCOZCASLP-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 355.48, ALogP 3.44, HBA 4, HBD 1, PSA 58.1, QED 0.84
Compound (SMILES): CC(C)C1CCC(N2CCC(n3c(=O)c(=O)[nH]c4ccccc43)CC2)CC1
InChIKey: GBRKRVVJROXVMX-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 369.51, ALogP 3.54, HBA 4, HBD 1, PSA 58.1, QED 0.84
Compound (SMILES): O=c1[nH]c2ccccc2n(C2CCN(C3Cc4cccc5cccc3c45)CC2)c1=O
InChIKey: UIPRRHHCLMYFHJ-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 4050 nM (pChEMBL 5.389999866485596)
Descriptors: MW 397.48, ALogP 3.78, HBA 4, HBD 1, PSA 58.1, QED 0.52
Compound (SMILES): NC(=O)Cn1c(=O)c(=O)n(C2CCN(C3Cc4cccc5cccc3c45)CC2)c2ccccc21
InChIKey: YCKODQWAIKYAQB-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 5450 nM (pChEMBL 5.260000228881836)
Descriptors: MW 454.53, ALogP 2.74, HBA 6, HBD 1, PSA 90.33, QED 0.48
Compound (SMILES): O=C1CC(=O)N(C2CCN(C3CCCCCCC3)CC2)c2ccccc2N1
InChIKey: ZAUHABBHHZLCNE-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 16200 nM (pChEMBL 4.789999961853027)
Descriptors: MW 369.51, ALogP 3.94, HBA 3, HBD 1, PSA 52.65, QED 0.8
Compound (SMILES): N#CCn1c(=O)c(=O)n(C2CCN(C3CCCCCCC3)CC2)c2ccccc21
InChIKey: NDTRDFOMRIWMBU-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 65660 nM (pChEMBL 4.179999828338623)
Descriptors: MW 394.52, ALogP 3.44, HBA 6, HBD 0, PSA 71.03, QED 0.75
Compound (SMILES): O=c1[nH]c2ncccc2n(C2CCN(C3CCCCCCC3)CC2)c1=O
InChIKey: CIMVAXZTJNDDRS-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 54760 nM (pChEMBL 4.260000228881836)
Descriptors: MW 356.47, ALogP 2.83, HBA 5, HBD 1, PSA 70.99, QED 0.84
Compound (SMILES): O=c1[nH]c2ccc(N3CCOCC3)cc2n(C2CCN(C3CCCCCCC3)CC2)c1=O
InChIKey: DUYDGIOXNYEFHX-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 52100 nM (pChEMBL 4.28000020980835)
Descriptors: MW 440.59, ALogP 3.28, HBA 6, HBD 1, PSA 70.57, QED 0.74
Compound (SMILES): O=c1[nH]c2ccccc2n([C@@H]2C[C@H]3CCC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: QVJLNGKSPRALSV-ACDBMABISA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 21900 nM (pChEMBL 4.659999847412109)
Descriptors: MW 395.55, ALogP 4.36, HBA 4, HBD 1, PSA 58.1, QED 0.77
Compound (SMILES): O=c1[nH]c2ccccc2n([C@H]2C[C@H]3C=C[C@@H](C2)N3C2/C=C\CCCCC2)c1=O
InChIKey: IQQOBQHEIOGKDI-IZVKAGQKSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 23400 nM (pChEMBL 4.630000114440918)
Descriptors: MW 377.49, ALogP 3.52, HBA 4, HBD 1, PSA 58.1, QED 0.64
Compound (SMILES): O=c1[nH]c2ccccc2n([C@@H]2C[C@H]3C=C[C@@H](C2)N3C2/C=C\CCCCC2)c1=O
InChIKey: IQQOBQHEIOGKDI-VNRYDWCLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 22800 nM (pChEMBL 4.639999866485596)
Descriptors: MW 377.49, ALogP 3.52, HBA 4, HBD 1, PSA 58.1, QED 0.64
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(F)c2F)[C@]12C(=O)Nc1cc(Cl)ccc12
InChIKey: CUMRPCQMSXHYEE-GRRGFIRHSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-Polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide.The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-beta Ala-beta Ala-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) Garcia-Echeverria et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. The Kd value of PMDM6-F with the recombinant MDM2 protein was determined from the saturation curve. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 ug/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 532.03, ALogP 4.4, HBA 4, HBD 4, PSA 90.46, QED 0.47
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2F)[C@]12C(=O)Nc1cc(F)c(F)cc12
InChIKey: MZLPNMUZFAVXQN-SDJDJFSXSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-Polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide.The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-beta Ala-beta Ala-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) Garcia-Echeverria et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. The Kd value of PMDM6-F with the recombinant MDM2 protein was determined from the saturation curve. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 ug/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 550.02, ALogP 4.54, HBA 4, HBD 4, PSA 90.46, QED 0.45
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2)[C@]12C(=O)Nc1cc(Cl)ccc12
InChIKey: DFNKYRCFAIHHQB-KCEIGVIJSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-Polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide.The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-beta Ala-beta Ala-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) Garcia-Echeverria et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. The Kd value of PMDM6-F with the recombinant MDM2 protein was determined from the saturation curve. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 ug/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 530.5, ALogP 4.77, HBA 4, HBD 4, PSA 90.46, QED 0.46
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2)[C@]12C(=O)Nc1cc(Cl)c(F)cc12
InChIKey: GRCKTMFGZSJBOA-ZYCFHTJLSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-Polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide.The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-beta Ala-beta Ala-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) Garcia-Echeverria et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. The Kd value of PMDM6-F with the recombinant MDM2 protein was determined from the saturation curve. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 ug/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 548.49, ALogP 4.91, HBA 4, HBD 4, PSA 90.46, QED 0.44
Compound (SMILES): O=C(c1ccccc1-c1ccccc1)N1CCC2CN(c3cnc4ccccc4n3)C2C1
InChIKey: HWBHNCKNXGKGOR-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat #SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 420.52, ALogP 4.65, HBA 4, HBD 0, PSA 49.33, QED 0.48
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(-c4ncccc4F)nn(C)c3n2)cc1
InChIKey: VHPHJZXOLJJSPJ-INIZCTEOSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 433.49, ALogP 4.04, HBA 6, HBD 1, PSA 81.93, QED 0.5
Compound (SMILES): Cc1ccc2c(n1)CC[C@@H]2NC(=O)COc1cc(C(F)F)c2c(C3CC3)nn(C)c2n1
InChIKey: BEZZNQFBPGIIIH-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 427.46, ALogP 3.67, HBA 6, HBD 1, PSA 81.93, QED 0.65
Compound (SMILES): COc1ccc2c(c1)CCC2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: NHKDZRLVFDFWKF-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 101 nM (pChEMBL 7)
Descriptors: MW 406.49, ALogP 3.35, HBA 6, HBD 1, PSA 78.27, QED 0.68
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: MJVATLQDOLXSMC-ZDUSSCGKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 414.46, ALogP 4.35, HBA 5, HBD 1, PSA 69.04, QED 0.62
Compound (SMILES): Cc1c(Cl)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1NCc1cnn(C)c1
InChIKey: KIYBJKHIYOZLEC-CABCVRRESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 384.87, ALogP 3.36, HBA 7, HBD 1, PSA 77.75, QED 0.63
Compound (SMILES): CC(C)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cc3)c2)c2cnc(N)nc21
InChIKey: ZJGWNGRVSUFGBL-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of human TrkC expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 448.91, ALogP 4.06, HBA 7, HBD 2, PSA 115.79, QED 0.43
Compound (SMILES): CC(C)n1cc(C(=O)c2cncc(NC(=O)Cn3ccc(C4CC4)n3)c2)c2cnc(N)nc21
InChIKey: YCLNSIOZHCMOPZ-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of human TrkC expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 444.5, ALogP 2.93, HBA 9, HBD 2, PSA 133.61, QED 0.42
Compound (SMILES): O=C(CC1COCCO1)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3OCO4)CC2)CC1
InChIKey: CFTKIUKLSZSRGT-LFKXIUMZSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Biochemical Assay: The ability of the compounds to bind to the 5-HT2A, D3 and D2 receptors was determined using radioligand binding to cloned receptors selectively expressed in HEK-293 EBNA cells.
Measurement: Ki = 529.67 nM (pChEMBL 6.28000020980835)
Descriptors: MW 458.6, ALogP 3.47, HBA 6, HBD 1, PSA 69.26, QED 0.67
Compound (SMILES): O=C(C[C@@H]1CCCO1)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3OCO4)CC2)CC1
InChIKey: LAGLIYNPBAJZEJ-BVSLBCMMSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Biochemical Assay: The ability of the compounds to bind to the 5-HT2A, D3 and D2 receptors was determined using radioligand binding to cloned receptors selectively expressed in HEK-293 EBNA cells.
Measurement: Ki = 531.19 nM (pChEMBL 6.28000020980835)
Descriptors: MW 442.6, ALogP 4.23, HBA 5, HBD 1, PSA 60.03, QED 0.68
Compound (SMILES): CC(C)(O)CC(=O)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3OCO4)CC2)CC1
InChIKey: TVKYQCPWDDYVLL-KESTWPANSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Biochemical Assay: The ability of the compounds to bind to the 5-HT2A, D3 and D2 receptors was determined using radioligand binding to cloned receptors selectively expressed in HEK-293 EBNA cells.
Measurement: Ki = 281.84 nM (pChEMBL 6.550000190734863)
Descriptors: MW 430.59, ALogP 3.82, HBA 5, HBD 2, PSA 71.03, QED 0.69
Compound (SMILES): O=C(CC1CCOCC1)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3OCO4)CC2)CC1
InChIKey: SGABQHZVZUGQTC-JKIUYZKVSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Biochemical Assay: The ability of the compounds to bind to the 5-HT2A, D3 and D2 receptors was determined using radioligand binding to cloned receptors selectively expressed in HEK-293 EBNA cells.
Measurement: Ki = 351.77 nM (pChEMBL 6.449999809265137)
Descriptors: MW 456.63, ALogP 4.48, HBA 5, HBD 1, PSA 60.03, QED 0.66
Compound (SMILES): CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3OCO4)CC2)CC1
InChIKey: WMLONRUBOXAPOV-UAPYVXQJSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Biochemical Assay: The ability of the compounds to bind to the 5-HT2A, D3 and D2 receptors was determined using radioligand binding to cloned receptors selectively expressed in HEK-293 EBNA cells.
Measurement: Ki = 52.74 nM (pChEMBL 7.28000020980835)
Descriptors: MW 401.55, ALogP 3.81, HBA 4, HBD 1, PSA 54.04, QED 0.82
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(CCCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: AMZWCCRFPBPFAY-UHFFFAOYSA-N
Target: Glutaminase liver isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UI32
Assay: Inhibition of GLS2 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 492.63, ALogP 4.32, HBA 8, HBD 2, PSA 109.76, QED 0.3
Compound (SMILES): Cc1c(Cl)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1NCc1cnn(C)c1
InChIKey: KIYBJKHIYOZLEC-CABCVRRESA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 384.87, ALogP 3.36, HBA 7, HBD 1, PSA 77.75, QED 0.63
Compound (SMILES): CC(C)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cc3)c2)c2cnc(N)nc21
InChIKey: ZJGWNGRVSUFGBL-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of dofetilide binding to human ERG
Measurement: Ki = 16900 nM (pChEMBL 4.769999980926514)
Descriptors: MW 448.91, ALogP 4.06, HBA 7, HBD 2, PSA 115.79, QED 0.43
Compound (SMILES): CC(C)n1cc(C(=O)c2cncc(NC(=O)Cn3ccc(C4CC4)n3)c2)c2cnc(N)nc21
InChIKey: YCLNSIOZHCMOPZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of dofetilide binding to human ERG
Measurement: Ki = 38900 nM (pChEMBL 4.409999847412109)
Descriptors: MW 444.5, ALogP 2.93, HBA 9, HBD 2, PSA 133.61, QED 0.42
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(CCCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: AMZWCCRFPBPFAY-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of human KGA preincubated for 15 to 30 mins followed by substrate addition and measured after 3 to 4 hrs by GDH-EZMTT reagent-based GDH coupled assay
Measurement: IC50 > 13000 nM (pChEMBL 4.886000156402588)
Descriptors: MW 492.63, ALogP 4.32, HBA 8, HBD 2, PSA 109.76, QED 0.3
Compound (SMILES): Cc1c(Cl)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1NCc1cnn(C)c1
InChIKey: KIYBJKHIYOZLEC-CABCVRRESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 384.87, ALogP 3.36, HBA 7, HBD 1, PSA 77.75, QED 0.63
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(CCCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: AMZWCCRFPBPFAY-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of human recombinant GAC (72 to 598 residues) expressed in Escherichia coli BL21(DE3) after 10 mins by GluO-horseradish peroxidase coupled assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 492.63, ALogP 4.32, HBA 8, HBD 2, PSA 109.76, QED 0.3
Compound (SMILES): Cc1c(Cl)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1NCc1cnn(C)c1
InChIKey: KIYBJKHIYOZLEC-CABCVRRESA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 384.87, ALogP 3.36, HBA 7, HBD 1, PSA 77.75, QED 0.63
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(CCCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: AMZWCCRFPBPFAY-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of GLS1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 492.63, ALogP 4.32, HBA 8, HBD 2, PSA 109.76, QED 0.3
Compound (SMILES): C[C@H](NC(=O)C1CC1)c1ccc(CN2CCc3cc(OCC(F)F)ccc3C2)cc1
InChIKey: VVDXIENLGSAKEJ-INIZCTEOSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/ml BSA, 3.75 mM reduced L-glutathione, 15 U/ml lactate dehydrogenase, 0.5 mM phosphoenolpyruvate, 15 U/ml pyruvate kinase, compounds at different concentrations at final DMSO concentrations of 1%.The enzymatic reaction is then started by addition of a mixture of NADH, acetyl Coenzyme A (both 2000 f.c.) and ATP (500 uM f.c.). The decrease of the optical density (slope S) is then determined at 25° C. at a wavelength of 340 nm over 15 minutes in a spectrophotometric reader.Each assay microtiter plate contains wells with vehicle instead of compound as controls for the non-inhibited enzyme (100% CTL; HIGH) and wells without acetyl-CoA as controls for non-specific NADH degradation (0% CTL; LOW).
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 414.5, ALogP 4.48, HBA 3, HBD 1, PSA 41.57, QED 0.69
Compound (SMILES): CC(C)(CO)C(=O)N(CCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)Cc1c(F)cccc1F.O=C(O)C(F)(F)F
InChIKey: MVZZEFFLPAQQJW-XQJPQCLXSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-diprenorphine from guinea pig kappa opioid receptor expressed in CHOK1 cell membranes
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 499.6, ALogP 3.82, HBA 4, HBD 2, PSA 86.87, QED 0.55
Compound (SMILES): COc1ccc(C2(c3cccc(NC(=O)c4ncc(Cl)cc4Cl)c3)CSC(N)=N2)cc1
InChIKey: GMISMHJPBMSIFP-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: 48.5 μL of substrate peptide solution (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) was added to each well of 96-hole half-area plate (a black plate: Corning Incorporated), and after addition of 0.5 μl of the test sample (dissolved in N,N′-dimethylformaldehyde) and 1 μl of Recombinant human BACE-1 (R&D Systems), the reaction mixture was incubated at 30° C. for 3 hours. The substrate peptide was synthesized by reacting Cryptate TBPCOOH mono SMP (CIS bio international) with Biotin-XSEVNLDAEFRHDSGC (Peptide Institute, Inc.). The final concentrations of the substrate peptide and Recombinant human BACE-1 were adjusted to 18 nM and 7.4 nM respectively, and the reaction was performed in sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-10).After the incubation for reaction, 50 μl of 8.0 μg/ml Streptavidin-XL665 (CIS bio international) dissolved in phosphate buffer (150 mM K2HPO4¿KH2PO4, pH 7.0, 0.008% Trit
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 473.39, ALogP 4.95, HBA 6, HBD 2, PSA 89.6, QED 0.55
Compound (SMILES): CN1CCC(Nc2nnc(C(=O)c3nc4ccc(-c5ccccc5)cc4s3)o2)C1=O
InChIKey: QTMQGCKSVSPKHX-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Enzymatic Assay: The enzymatic assay was measured using white, opaque 96-well half area plates. Each well contained 60 μL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 2 ul of a DMSO solution containing compound of interest. Conditioned media obtained from HT-1080 cells, which were transformed by RAGE technology (Athersys) to overexpress endogenous EL, was added and the reaction was allowed to incubate for 20 min at 37° C. with gentle agitation. The reaction was started by the addition of 20 μL of a 1:4 dilution of vesicles. The final total reaction volume was 100 μL. The reaction rates were measured on a Gemini plate reader with an excitation wavelength of 488 nm and an emission of 530 nm. Readings were taken every 20 seconds for 10 min with agitation between each reading.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 419.47, ALogP 3.22, HBA 8, HBD 1, PSA 101.22, QED 0.5