lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCN(/C(=N/O)c3ccc(O)cc3)CC2)cc1
InChIKey: OGXFNEAZYVDSMA-HTXNQAPBSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 1179.4 nM (pChEMBL 5.929999828338623)
Descriptors: MW 376.44, ALogP 1, HBA 6, HBD 3, PSA 119.46, QED 0.32
Compound (SMILES): CC[C@H]1CN(Cc2cc(C)cc(CC(=O)O)c2)CCN1c1nc2ccc(C(F)(F)F)cc2s1
InChIKey: ZBKXSRSXIGZPCY-IBGZPJMESA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 477.55, ALogP 5.35, HBA 5, HBD 1, PSA 56.67, QED 0.52
Compound (SMILES): CCCCOc1nc(N)c2[nH]cc(Cc3ccc(CN4CCCC4)cc3)c2n1
InChIKey: VMDGIQUJSYPMLF-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: In Vitro Receptor Binding Activity Screening Assay: Reagents:HEK-blue hTLR7 cell and HEK-blue hTLR8 cell (available from InvivoGen)DMEM mediumheat inactivated fetal bovine serumAnti Mycoplasma reagent Normocin bleomycinblasticidinScheme:1. Preparation of 96-well compound plate:The compounds were gradient diluted with DMSO in 3-fold using liquid work station POD starting at a concentration of 10 mmol/L and 10 points were diluted (2nd column to 11th column, and each point was duplicated). At 12th column, 1 μL of 5 mg/mL positive compound R848 was added as positive control; and at 1st column, 1 μL of DMSO was added as negative control. Each well contained 1 μL of DMSO.2. The cells in culture flask were collected and the cell density was diluted to 250,000 cells/mL.3. 200 μL (50,000 cells/well) of cell suspension was added into prepared compound plate and the final concentration of DMSO in each well was 0.5%.4. The culture plates containing cells and the compounds were incubated in CO2 incubator for 24 h at 37° C., 5% CO2.5. After 24 h incubation, 20 μL of supernatant was removed from each well to a 96-well transparent assay plate. To each well of the assay plate was added 180 μL of Quanti-Blue reagent and the plate was incubated in an incubator at 37° C., 5% CO2 for 1 h.6. After 1 h, the content of alkaline phosphatase in 20 μL of supernatant was determined using Microplate Reader OD650.7. EC50 of each compound was obtained with Prism software.
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 379.51, ALogP 3.91, HBA 5, HBD 2, PSA 80.06, QED 0.58
Compound (SMILES): c1ccc(-c2csc(-c3csc(Nc4ccc(N5CCOCC5)cc4)n3)n2)cc1
InChIKey: GFHGWOSXNHSKCL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 2863 nM (pChEMBL 5.539999961853027)
Descriptors: MW 420.56, ALogP 5.51, HBA 7, HBD 1, PSA 50.28, QED 0.46
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(O)cn2)cc1Nc1ccccc1Cl
InChIKey: BDFXWFUXDCODKM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-fused JAK1 (866 to 1154 residues) (unknown origin) using FITC-AhxKKSRGDYMTMQIG-NH2 peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): O=C(NO)c1ccc(NC(=O)[C@@H](NS(=O)(=O)c2cccc3ccccc23)c2ccccc2)cc1
InChIKey: UZYFIQWENUALSN-QHCPKHFHSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using fluorogenic as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 23.1 nM (pChEMBL 7.639999866485596)
Descriptors: MW 475.53, ALogP 3.62, HBA 5, HBD 4, PSA 124.6, QED 0.24
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(=O)N3CCOCC3)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: FWTDDBIMDSVPTR-AATRIKPKSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged BRD4 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 451.52, ALogP 3.37, HBA 6, HBD 1, PSA 85.79, QED 0.58
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: PXHIFOLPKHLYBX-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 1039.63
Compound (SMILES): CC(=O)N1c2ncc(NC(=O)OCC(C)(C)C)cc2C2(CCCCC2)C1(C)C
InChIKey: JEBYINCSVWJRSR-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 5670 nM (pChEMBL 5.25)
Descriptors: MW 387.52, ALogP 5.02, HBA 4, HBD 1, PSA 71.53, QED 0.77
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)[nH]1
InChIKey: WNBJBSFSPKVIPC-SANMLTNESA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 539.68, ALogP 4.52, HBA 6, HBD 3, PSA 118.84, QED 0.22
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Cc1cccc(F)c1C1CCNCC1
InChIKey: QIDVCXQDTQASFN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin)
Measurement: IC50 = 372 nM (pChEMBL 6.429999828338623)
Descriptors: MW 424.52, ALogP 2.65, HBA 7, HBD 2, PSA 80.71, QED 0.67
Compound (SMILES): CCCOc1nc(-c2cncc(C3COB(O)C3)c2)c(F)cc1OC
InChIKey: CECUZGKZZDAYHR-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Cytokine Assays: Cytokine inhibitory activity is determined by measuring the effect of test agent on the release of the cytokines IL-4, IL-13 and IFNγ from human peripheral blood mononuclear cells (PBMCs) stimulated with the T-cell mitogen phytohemagglutinin-L (PHA-L). At the time of assay, human PBMCs (Astarte Biologics) are removed from cryopreservation, thawed quickly at 37° C., diluted in assay medium (RPMI-Gibco 1640 medium, 10% heat inactivated fetal bovine serum (HIFBS), 2 mM glutamine and 10 mM HEPES pH 7.4) and then centrifuged at 250×g for 5 minutes. The resulting cell pellet is re-suspended in assay medium to a concentration of approximately 5×106 cells/mL and 50 μL of this cell suspension (approximately 250,000 cells) is added to each well of a 384-well cell culture microtiter plate (Perkin Elmer). Varying concentrations of test compound are then diluted in assay medium and added to the assay plate wells in a volume of 25 μL. After −10 minutes at room temperature (21° C.) the cells are stimulated by the addition of 25 μL of PHA-L (14 μg/mL; Millipore) and the assay plate is placed in an incubator at 37° C. in a humidified environment in 5% carbon dioxide. The final assay conditions are approximately 250,000 human PBMCs per well in assay medium containing 3.5 μg/mL PHA-L and the indicated final concentration of test compound (approximately 10 μM to 9.5 μM by 4-fold dilution). The final concentration of DMSO in the assay is approximately 0.25%. After 48 hours, the assay plate is removed from the incubator and centrifuged at 250×g for 5 minutes. A portion of the resulting cell supernatant is then used to determine the amount of IL-4, IL-13 and IFNγ in each well. Cytokine measurements are made using human IL-4, IL-13 or IFNγ HTRF assay kits (CisBio) following the manufacturer's assay protocol. The concentrations and resulting effect values for tested compounds are plotted and the concentration of compound required for 50% effect (IC50) is determined with a four-parameter logistic dose response equation (E-WorkBook, ID Business Solutions Ltd.).
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 346.17
Compound (SMILES): Oc1ccc2[nH]c3c(-c4c[nH]c5ccccc45)nccc3c2c1
InChIKey: AESLFLSZEVKRCB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Binding affinity to 5-HT2BR (unknown origin) assessed as inhibition constant
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 299.33, ALogP 4.57, HBA 2, HBD 3, PSA 64.7, QED 0.42
Compound (SMILES): CCCNNC(=O)c1ccc(Br)cc1
InChIKey: OTHBGAGRQLSYFV-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 257.13, ALogP 2.09, HBA 2, HBD 2, PSA 41.13, QED 0.64
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-GOSISDBHSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 513 nM (pChEMBL 6.289999961853027)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): C[C@@H]1OC(=O)NN=C1c1ccc(-c2ccc(F)cc2)c(C(F)(F)F)c1
InChIKey: JNTJTCXFIXNXDV-VIFPVBQESA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: PDE3A Enzyme Inhibition: The commercially available 3H-cAMP Scintillation Proximity Assay (SPA, Perkin Elmer) system was used for enzyme inhibition studies. For the determination of the in vitro effect of example compounds on the PDE3A reactions 2 μl of the respective example compound solution in DMSO (serial dilutions) were placed in wells of microtiter plates (Isoplate-96/200W; Perkin Elmer). 50 μl of a dilution of PDE3A cell extract from Sf9 cells overexpressing human full length PDE3A (SB Drug Discovery, UK) in buffer A (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA) was added. The dilution of the PDE3A cell extract was chosen such that the reaction kinetics was linear and less than 70% of the substrate was consumed (typical dilution 1:5000). The reaction was started by addition of 50 μl (0.025 μCi) of 1:2000 in buffer A w/o BSA diluted substrate [8-3H]adenosine 3′, 5′-cyclic phosphate (1 μCi/μl; Perkin Elmer). After incubation at room temperature for 60 min, the reaction was stopped by addition of 25 μl of a suspension containing 18 mg/ml yttrium scintillation proximity beads (Perkin Elmer) in water. The microtiter plates were sealed and measured in a Microbeta scintillation counter (PerkinElmer Wallac). IC50 values were determined from sigmoidal curves by plotting percentage PDE3A activity vs log compound concentration.
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 352.29, ALogP 4.34, HBA 3, HBD 1, PSA 50.69, QED 0.82
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)C[C@H]2C)c1
InChIKey: HUAKZZAZJGNQFD-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: QKXAMYHLNVXQGM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 1610 nM (pChEMBL 5.789999961853027)
Descriptors: MW 408.54, ALogP 5.25, HBA 5, HBD 1, PSA 54.7, QED 0.33
Compound (SMILES): C[C@@H]1CCN(C(=O)N2CCOCC2)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
InChIKey: ZCNULYRSWVMPIQ-DOMZBBRYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 384.44, ALogP 1.54, HBA 5, HBD 2, PSA 99.25, QED 0.66
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2cc(Br)ccc2O3)c([N+](=O)[O-])c1
InChIKey: FWVJADLNFOKENV-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 496.34, ALogP 3.01, HBA 7, HBD 1, PSA 132.84, QED 0.51
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)OC(C)(C)C)nc2C2(CCC(F)(F)CC2)C1(C)C
InChIKey: XKFMPILHYHITMK-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 410.47, ALogP 4.42, HBA 5, HBD 1, PSA 84.42, QED 0.74
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1
InChIKey: XZPVJOHSMQBKNV-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at human SST2 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 440.5, ALogP 5.65, HBA 4, HBD 1, PSA 65.94, QED 0.45
Compound (SMILES): N#C/C(=C/C(=O)N1CCC[C@@H](n2nc(-c3cnc4[nH]ccc4c3)c3c(N)ncnc32)C1)C1CC1
InChIKey: XUAVCXINBQWRAV-YZIPPPLESA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin)
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 453.51, ALogP 2.98, HBA 8, HBD 2, PSA 142.4, QED 0.36
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3ccc(F)cc3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: SZPOIQZUDFAZMU-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 416.44, ALogP 5.21, HBA 4, HBD 3, PSA 82.28, QED 0.37
Compound (SMILES): CCc1sc(-c2csc(Nc3cc(OC)cc(OC)c3)n2)nc1-c1ccccc1
InChIKey: XTWLRMXVIARWFU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 5246 nM (pChEMBL 5.28000020980835)
Descriptors: MW 423.56, ALogP 6.26, HBA 7, HBD 1, PSA 56.27, QED 0.38
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: IAJUDDNMGIAOGZ-XRVGGGAJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 926.14, ALogP -4.18, HBA 13, HBD 15, PSA 413.68, QED 0.02
Compound (SMILES): COc1cccc(-c2csc(-c3csc(Nc4ccc(N5CCOCC5)cc4)n3)n2)c1
InChIKey: ZRVJXOLNOGRHKM-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 4674 nM (pChEMBL 5.329999923706055)
Descriptors: MW 450.59, ALogP 5.52, HBA 8, HBD 1, PSA 59.51, QED 0.42
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C#N)c2)c2cc(C)[nH]c2c1=O
InChIKey: BQAKOVGAYWUDIT-ONEGZZNKSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged BRD4 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 13500 nM (pChEMBL 4.869999885559082)
Descriptors: MW 416.48, ALogP 3.23, HBA 5, HBD 1, PSA 91.12, QED 0.66
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3ncc4c(=O)n(C5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: AGULKNIKZOLEFC-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 246 nM (pChEMBL 6.610000133514404)
Descriptors: MW 568.73, ALogP 4.76, HBA 10, HBD 2, PSA 104.34, QED 0.31
Compound (SMILES): O=C(CCCCCCNCc1ccc(F)cc1)NO
InChIKey: SJHLXQGXRUFBKJ-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 268.33, ALogP 2.37, HBA 3, HBD 3, PSA 61.36, QED 0.37
Compound (SMILES): CSc1cc(-c2cnc(N)c(OC(F)F)n2)nc(N2C[C@@H]3C[C@H]2CO3)n1
InChIKey: XYWGNKCGTAROOP-YUMQZZPRSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 382.4, ALogP 1.82, HBA 9, HBD 1, PSA 99.28, QED 0.61
Compound (SMILES): COc1cc(N2CCC(N(C)C)CC2)ccc1Nc1ncc(Cl)c(Nc2cccc3c2B(O)OC3)n1
InChIKey: BKJCLHFYGLDIJR-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK cytoplasmic domain (1058 to 1620 residues) L1196M mutant expressed in baculovirus-infected Sf21 cells using LANCE Ultra ULight-PolyGT substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 508.82
Compound (SMILES): C[C@@H]1CCN(C(=O)Cn2cnnn2)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
InChIKey: MYAASZBFDPOUNO-MFKMUULPSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 381.4, ALogP 0.3, HBA 8, HBD 2, PSA 130.38, QED 0.52
Compound (SMILES): Nc1ncc(-c2cc(N3CCC(F)(F)C3)nc(N3C[C@@H]4C[C@H]3CO4)c2)nc1OC(F)F
InChIKey: CMXUWUGBGXEFFR-RYUDHWBXSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 440.4, ALogP 2.55, HBA 8, HBD 1, PSA 89.63, QED 0.71
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccc(C(F)(F)F)cc1
InChIKey: LQBVXWVKJXJFSJ-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 3330 nM (pChEMBL 5.480000019073486)
Descriptors: MW 538.98, ALogP 6.07, HBA 4, HBD 1, PSA 75.71, QED 0.43
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc(Cl)c(Nc2cccc3c2B(O)OC3)n1
InChIKey: KSQSHZHRYLLNCV-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK cytoplasmic domain (1058 to 1620 residues) L1196M mutant expressed in baculovirus-infected Sf21 cells using LANCE Ultra ULight-PolyGT substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 563.9
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCCCN(C)Cc1ccc(OC)c(OC)c1
InChIKey: VNMUKEWBYJPDPC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 44960 nM (pChEMBL 4.349999904632568)
Descriptors: MW 522.73, ALogP 7.51, HBA 6, HBD 0, PSA 52.93, QED 0.12
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NC(=O)C2CCN(C(=O)OCc3ccccc3)CC2)CC1
InChIKey: FCORXOBTLFNQOU-NOCHOARKSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 639.8, ALogP 3.83, HBA 8, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): COCC(NC(=O)C1CCCC1)C(=O)Nc1nnc(Cc2ccc([N+](=O)[O-])cc2)s1
InChIKey: DAAFRPNNICESHO-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75604
Assay: Inhibition of human His-tagged USP2 (259 to 605 residues) using ubiquitin rhodamine 110 110 as substrate preincubated for 15 to 20 mins followed by enzyme addition and measured after 25 mins by fluorometric assay
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 433.49, ALogP 2.3, HBA 8, HBD 2, PSA 136.35, QED 0.46
Compound (SMILES): O=C(CCCCCCNc1nc2ccccc2nc1-c1nc2ccccc2o1)NO
InChIKey: UPTYYNWPPBPUMA-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 15.47 nM (pChEMBL 7.809999942779541)
Descriptors: MW 405.46, ALogP 4.31, HBA 7, HBD 3, PSA 113.17, QED 0.22
Compound (SMILES): COc1ccc(S(=O)(=O)N(Cc2ccccn2)c2c(C)cc(-c3cccc(C(F)(F)F)c3)cc2C(=O)NO)cc1
InChIKey: HJPPIRCRVNMSQH-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 571.58, ALogP 5.6, HBA 6, HBD 2, PSA 108.83, QED 0.21
Compound (SMILES): COc1ccc(/C=N/NC(=O)CCCCCCCC(=O)NO)cc1
InChIKey: GAZWXVIVAKKMPK-QGOAFFKASA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 incubated for 20 mins by HDAC Glo assay
Measurement: IC50 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 335.4, ALogP 2.38, HBA 5, HBD 3, PSA 100.02, QED 0.25
Compound (SMILES): Cc1ccc(S(=O)(=O)NC(=O)c2cc(C(=O)O)ccn2)cc1
InChIKey: XTGQLLNXJPAVEA-UHFFFAOYSA-N
Target: Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96Q83
Assay: Inhibition of human ALKBH3 expressed in Escherichia coli BL21 (DE3) Rosetta cells
Measurement: IC50 = 23300 nM (pChEMBL 4.630000114440918)
Descriptors: MW 320.33, ALogP 1.21, HBA 5, HBD 2, PSA 113.43, QED 0.87
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C(C)(C)N(C)C)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: AOFDLXVBRYIAGS-QHCPKHFHSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2
Measurement: IC50 < 3.5 nM (pChEMBL 8.456000328063965)
Descriptors: MW 494.64, ALogP 5.33, HBA 7, HBD 1, PSA 97.56, QED 0.32
Compound (SMILES): Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(S(=O)(=O)[N-]C(=O)CCCCC3CCSS3)cc2)cc1.[Na+]
InChIKey: RNDSYJOBGICVGK-UHFFFAOYSA-M
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Inhibition of TRPV1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 569.7, ALogP 6.39, HBA 7, HBD 1, PSA 81.06, QED 0.24
Compound (SMILES): COCC(NC(=O)C1CCOCC1)C(=O)Nc1nnc(Cc2ccc([N+](=O)[O-])cc2)s1
InChIKey: ZTUXPKUNPNABDT-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75604
Assay: Inhibition of human His-tagged USP2 (259 to 605 residues) using ubiquitin rhodamine 110 110 as substrate preincubated for 15 to 20 mins followed by enzyme addition and measured after 25 mins by fluorometric assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 449.49, ALogP 1.53, HBA 9, HBD 2, PSA 145.58, QED 0.43
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4ccccc4Cl)cs3)cs2)cc(OC)c1
InChIKey: AEAFALBSVDOECI-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 429.95, ALogP 6.35, HBA 7, HBD 1, PSA 56.27, QED 0.39
Compound (SMILES): COc1ccc(OC)c(-n2nnc(C(=O)Nc3cc(C(C)(C)C)ccc3OCCN(C)C)c2C)c1
InChIKey: XIRSIGXLFLHAQR-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 481.6, ALogP 4.08, HBA 8, HBD 1, PSA 90.74, QED 0.49
Compound (SMILES): COc1ccccc1NC(=O)Nc1ccc2n(c1=O)C[C@@H]1C[C@H]2CN(C(=O)c2ccc3ccccc3c2)C1
InChIKey: PODWOVPWRPULPI-XXBNENTESA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human 20S immuno proteosome beta5i subunit using Suc-LLVY-AMC as substrate measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 508.58, ALogP 4.91, HBA 5, HBD 2, PSA 92.67, QED 0.41
Compound (SMILES): COc1ccc(-c2cnc(NC(=O)CCCCCCNC(=O)C(O)(O)C(F)(F)F)s2)cc1
InChIKey: LBYUKUIOYGHLJO-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant HDAC3 (unknown origin) incubated for 3 hrs by chemiluminescent assay
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 475.49, ALogP 3.07, HBA 7, HBD 4, PSA 120.78, QED 0.29
Compound (SMILES): Oc1cc(-c2ncc3c(N4CCCC5(CCO5)C4)nc(OC[C@@]45CCCN4C[C@H](F)C5)nc3c2F)c2c(F)c(F)ccc2c1
InChIKey: WPBKOEMZXRETQS-VIZGZJEGSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12D mutant in human ASPC1 cells assessed as reduction in ERK1/2 phosphorylation level incubated for 2 hrs by MSD assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 609.62, ALogP 5.68, HBA 8, HBD 1, PSA 83.84, QED 0.29
Compound (SMILES): C=CC(=O)N1CCCCCCn2cc(c3ccccc32)-c2ccnc(n2)Nc2cc1ccc2OC
InChIKey: XJXDTLCWUFYVIB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant (unknown origin)
Measurement: IC50 = 8.31 nM (pChEMBL 8.079999923706055)
Descriptors: MW 467.57, ALogP 5.94, HBA 6, HBD 1, PSA 72.28, QED 0.37
Compound (SMILES): O=C1CCc2cc(OCCN3CCC[C@@H]3c3cccc(F)c3)ccc2N1
InChIKey: ZHGIASFMHGIOQA-HXUWFJFHSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of full length human ALDH1A1 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 354.43, ALogP 3.93, HBA 3, HBD 1, PSA 41.57, QED 0.88
Compound (SMILES): O=c1c(OS(=O)(=O)[O-])c(-c2ccc(OS(=O)(=O)O)c(OS(=O)(=O)[O-])c2)oc2cc(OS(=O)(=O)O)cc(OCCOc3cc(-c4oc5cc(OS(=O)(=O)[O-])cc(OCCOc6cc(OS(=O)(=O)[O-])cc7oc(-c8ccc(OS(=O)(=O)[O-])c(OS(=O)(=O)[O-])c8)c(OS(=O)(=O)[O-])c(=O)c67)c5c(=O)c4OS(=O)(=O)[O-])ccc3OS(=O)(=O)[O-])c12.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[NaH]
InChIKey: IFEXYZXEVCTAKO-UHFFFAOYSA-E
Target: Coagulation factor XIII A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00488
Assay: Inhibition of human coagulation factor XIIIa assessed as inhibition of factor 13a mediated fibrin polymerization incubated for 24 hrs by SDS-PAGE analysis
Measurement: IC50 = 76300 nM (pChEMBL 4.119999885559082)
Descriptors: MW 1839.49
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3ccc(=O)n(C4CCCCCC4)c3n2)CC1
InChIKey: NIVRVOZNYYXNJT-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 419.55, ALogP 2.52, HBA 7, HBD 1, PSA 97.19, QED 0.77
Compound (SMILES): COc1ccccc1-n1cc(C#N)c2ncnc(N3CCN(Cc4ccccc4)CC3)c21
InChIKey: ORLUZZMIGGWQRW-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin) expressed in dog MDCK-II cells using pheophorbide A as substrate preincubated for 20 mins followed by substrate addition and measured after 120 mins by flow cytometry analysis
Measurement: IC50 = 37900 nM (pChEMBL 4.420000076293945)
Descriptors: MW 424.51, ALogP 3.62, HBA 7, HBD 0, PSA 70.21, QED 0.49
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc(-c5ccccc5)cc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: DRUJOKCPVUXITN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: P39051
Assay: Inhibition of HIS-tagged recombinant Trypanosoma brucei TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 622.82, ALogP 4.96, HBA 7, HBD 2, PSA 102.18, QED 0.13
Compound (SMILES): Fc1ccc(OC[C@@H]2CN(Cc3ccc4[nH]cnc4c3)CCO2)cc1F
InChIKey: MSYCGACUZCZLFO-HNNXBMFYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 426 nM (pChEMBL 6.369999885559082)
Descriptors: MW 359.38, ALogP 3.12, HBA 4, HBD 1, PSA 50.38, QED 0.76
Compound (SMILES): COC(=O)c1cnc(Nc2ccc(N3CCN(C)CC3)cc2OC)nc1-c1cn(C)c2ccccc12
InChIKey: RKOUWTODJFUNPG-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/C797S mutant (unknown origin) using TK-substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 20 mins by HTRF assay
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 486.58, ALogP 3.93, HBA 9, HBD 1, PSA 84.75, QED 0.41
Compound (SMILES): O=C(Nc1cccnc1)c1ccnn2cc(-c3ccccc3)nc12
InChIKey: UVTJZQHSPPYGDG-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Inhibition of Tau (unknown origin) phosphorylation
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 315.34, ALogP 3.04, HBA 5, HBD 1, PSA 72.18, QED 0.63
Compound (SMILES): COCCn1c(=O)c2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: UOFKPXJMZQVPLP-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 1483 nM (pChEMBL 5.829999923706055)
Descriptors: MW 518.62, ALogP 2.35, HBA 11, HBD 2, PSA 113.57, QED 0.36
Compound (SMILES): CCN(CCN(C)C)C(=O)CNCc1cc(C(=O)N(C)C)ccn1
InChIKey: VHKSSHRSJGZQOV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin ) by Alphascreen assay
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 335.45, ALogP 0.28, HBA 5, HBD 1, PSA 68.78, QED 0.7
Compound (SMILES): CCCOC(c1ccccc1)c1cccc(NC(=O)c2cc(C(F)(F)F)nn2-c2cccc(CN)c2)c1
InChIKey: ODVQLXVRAUDBCL-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader.
Measurement: Ki > 75 nM (pChEMBL 7.125)
Descriptors: MW 508.54, ALogP 6.12, HBA 5, HBD 2, PSA 82.17, QED 0.29
Compound (SMILES): Nc1ncc(-c2cc(C3CC3)cc(N3C[C@@H]4C[C@H]3CO4)n2)nc1OC(F)F
InChIKey: GIRIQGHXPJDILQ-RYUDHWBXSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 375.38, ALogP 2.58, HBA 7, HBD 1, PSA 86.39, QED 0.86
Compound (SMILES): COCC(NC(=O)c1ccccc1)C(=O)Nc1nnc(Cc2ccc([N+](=O)[O-])cc2)s1
InChIKey: AJEVBUJADPHFFP-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75604
Assay: Inhibition of human His-tagged USP2 (259 to 605 residues) using ubiquitin rhodamine 110 110 as substrate preincubated for 15 to 20 mins followed by enzyme addition and measured after 25 mins by fluorometric assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 441.47, ALogP 2.42, HBA 8, HBD 2, PSA 136.35, QED 0.38
Compound (SMILES): CN1CCc2cc(Nc3ncc4c(=O)n(C5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)ccc2C1
InChIKey: NHBSXIGAYOREOT-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 511.63, ALogP 4.22, HBA 9, HBD 2, PSA 101.1, QED 0.39
Compound (SMILES): Nc1ccc2[nH]c3c(c2c1)CCn1c-3nc2ccccc2c1=O
InChIKey: ROZJKNASHFBEGF-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 2578 nM (pChEMBL 5.590000152587891)
Descriptors: MW 302.34, ALogP 2.68, HBA 4, HBD 2, PSA 76.7, QED 0.49
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccc(OC(F)(F)F)cc2)CCC1(O)c1cccc(O)c1
InChIKey: BAGLDFCFYIPXQM-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 93.6 nM (pChEMBL 7.03000020980835)
Descriptors: MW 452.47, ALogP 3.13, HBA 5, HBD 2, PSA 73.24, QED 0.7
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n([C@@H]5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: JJEGWIJBJXWVDU-HSZRJFAPSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of human full length GST-tagged WEE1 expressed in insect cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 540.67, ALogP 3.98, HBA 10, HBD 2, PSA 104.34, QED 0.35
Compound (SMILES): Cc1ccc2c(=O)[nH]c(-c3ccc([C@@](C)(O)CO)cc3)cn12
InChIKey: AOMPHWKJTUPEOB-KRWDZBQOSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 748 nM (pChEMBL 6.130000114440918)
Descriptors: MW 298.34, ALogP 1.8, HBA 4, HBD 3, PSA 77.73, QED 0.69
Compound (SMILES): Fc1ccc(CN2CCCC23CCN(Cc2cn4ccccc4n2)C3)cc1F
InChIKey: MZEWTMVKHJXAGJ-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 382.46, ALogP 3.85, HBA 4, HBD 0, PSA 23.78, QED 0.68
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)ccc2N2C[C@H]3C[C@@H]2CN3)n1
InChIKey: JKHBVOCOHYSWTQ-HUUCEWRRSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 1690 nM (pChEMBL 5.769999980926514)
Descriptors: MW 437.45, ALogP 3.23, HBA 6, HBD 2, PSA 79.38, QED 0.64
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3ccc4ccccc4n3)C3CCN2CC3)c1
InChIKey: CAYMRNQWSQYOLB-IRLDBZIGSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Binding affinity to alpha3beta4 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 345.45, ALogP 3.71, HBA 4, HBD 0, PSA 38.25, QED 0.72
Compound (SMILES): CC1(C)Cn2c(CC(=O)O)c(-c3ccc(Cl)cc3)c(-c3ccccc3)c2C1=O
InChIKey: HXFGFGZDOOZLTH-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin)
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 393.87, ALogP 5.33, HBA 3, HBD 1, PSA 59.3, QED 0.65
Compound (SMILES): COc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: QWJHDFPZYMYNPX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-fused JAK1 (866 to 1154 residues) (unknown origin) using FITC-AhxKKSRGDYMTMQIG-NH2 peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 369.81, ALogP 3.72, HBA 6, HBD 3, PSA 102.16, QED 0.61
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(N(S(=O)(=O)c3ccc([N+](=O)[O-])cc3)S(=O)(=O)c3ccc([N+](=O)[O-])cc3)ccc21
InChIKey: BIKNVGUTLNWXJC-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 612.6, ALogP 4.27, HBA 10, HBD 0, PSA 191.25, QED 0.2
Compound (SMILES): [N-]=[N+]=Nc1ccc(/C=C/c2ccc(N=[N+]=[N-])cc2S(=O)(=O)[O-])c(S(=O)(=O)[O-])c1.[Na+].[Na+]
InChIKey: HYYYTIDWAIQGHI-SEPHDYHBSA-L
Target: DNA repair protein RAD51 homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06609
Assay: Inhibition of wild type human RAD51 expressed in Escherichia coli BL21-DE3 using 100 bp ssDNA probe as substrate assessed as prevention of D-loop formation preincubated for 5 mins followed by plasmid DNA addition and measured after 15 mins by agarose gel electrophoresis method
Measurement: IC50 = 44300 nM (pChEMBL 4.349999904632568)
Descriptors: MW 422.4, ALogP 4.23, HBA 6, HBD 2, PSA 206.26, QED 0.23
Compound (SMILES): COc1ccccc1-n1c(=O)c2cnc(Nc3ccc4c(c3)CNCC4(C)C)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: NGQGJGXHPKUCEQ-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 224 nM (pChEMBL 6.650000095367432)
Descriptors: MW 551.65, ALogP 4.33, HBA 10, HBD 3, PSA 119.12, QED 0.29
Compound (SMILES): COc1ccc(-c2ccncc2NC(=O)c2ccnc(NC(=O)C3CC3)c2)cc1
InChIKey: CSJHKAPXYLZAOS-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 388.43, ALogP 3.75, HBA 5, HBD 2, PSA 93.21, QED 0.67
Compound (SMILES): CCCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: OEBTWRYFDAUETA-ZMBIFBSDSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonist activity against recombinant human adrenergic alpha1A receptor expressed in Rat1 cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 467.01, ALogP 4.02, HBA 5, HBD 1, PSA 67.23, QED 0.52
Compound (SMILES): CCC(=O)c1sc(-c2cccc(F)c2)nc1O
InChIKey: ANUOYWLYYBOAMH-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in ethyl 4-methoxy-2-phenylthiazole-5-carboxylate induced Ca2+ efflux preincubated for 5 mins followed by ethyl 4-methoxy-2-phenylthiazole-5-carboxylate addition and measured for 3 mins by FLIPR assay
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 251.28, ALogP 3.25, HBA 4, HBD 1, PSA 50.19, QED 0.85
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(N)c(C(=O)NCc3cncnc3)cc21
InChIKey: KFIKODBQLOMHNX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.38, ALogP 0.97, HBA 8, HBD 2, PSA 120.2, QED 0.52
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(CC)c(OC)c4)nn32)CC1
InChIKey: LBCWQLSBINGIBS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 467.57, ALogP 3.01, HBA 7, HBD 2, PSA 111.71, QED 0.61
Compound (SMILES): CN(C)c1ccc(C(=O)NNCC2CCCC2)cc1
InChIKey: LJBJHPWKSLDVNC-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 1760 nM (pChEMBL 5.75)
Descriptors: MW 261.37, ALogP 2.18, HBA 3, HBD 2, PSA 44.37, QED 0.8
Compound (SMILES): COc1cc(C)c(C)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)C1CC1
InChIKey: HVQFRZHUCLHYKM-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 414.53, ALogP 3.8, HBA 4, HBD 1, PSA 75.71, QED 0.81
Compound (SMILES): Cc1c2c(cc[n+]1Cc1ccccc1)c1ccc(OCc3ccc(F)cc3)cc1n2CCCc1ccccc1.[Br-]
InChIKey: VAEDWPRHZUZXDX-UHFFFAOYSA-M
Target: Serine/threonine-protein kinase PLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4B4
Assay: Inhibition of PLK3 (unknown origin)
Measurement: IC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 515.65, ALogP 7.79, HBA 2, HBD 0, PSA 18.04, QED 0.18
Compound (SMILES): COc1ccc(/C=C/C(=N/Oc2ccc(/C=C/C(=O)c3ccc(F)cc3)cc2)c2ccc(OC)cc2)cc1
InChIKey: XRWOGUBTQNJHSD-NAYFDBJDSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of MAO-B (unknown origin)
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 507.56, ALogP 7.24, HBA 5, HBD 0, PSA 57.12, QED 0.1
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc3c(cnn3C)c2N2CC[C@@H](N)C2)n1
InChIKey: UKFXFNQXCIZAEM-CQSZACIVSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 461.5, ALogP 2.97, HBA 8, HBD 2, PSA 111.19, QED 0.47
Compound (SMILES): Cn1cnc2c(c(-c3cc(Cl)c(O)c(C(N)=O)c3)cn2CC(=O)Nc2cc(N3CCOCC3)ncc2Cl)c1=O
InChIKey: LYPIBXVPZCTMSW-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 10 nM (pChEMBL 8)
Descriptors: MW 572.41, ALogP 2.38, HBA 10, HBD 3, PSA 157.6, QED 0.32
Compound (SMILES): Nc1ncc(-c2cc([C@H]3CCCO3)nc(N3C[C@@H]4C[C@H]3CO4)n2)nc1OC(F)F
InChIKey: AKKHHVJIISFQCL-PKFCDNJMSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 406.39, ALogP 1.95, HBA 9, HBD 1, PSA 108.51, QED 0.8