lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)CCNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O
InChIKey: NWSKLDYVCQCAPY-OQLLNIDSSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full length C-terminal FLAG-tagged human HDAC2 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.15, ALogP 1.12, HBA 5, HBD 4, PSA 119.22, QED 0.35
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)CC4)c(F)cn2)C1
InChIKey: ZNUJHRYFOFHSMX-JKSUJKDBSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MV4-11 cells assessed as induction of caspase-3/7 activation measured after 6 hrs followed by Caspase-glo reagent based assay
Measurement: EC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 427.52, ALogP 3.69, HBA 5, HBD 2, PSA 88.91, QED 0.78
Compound (SMILES): C/C=C/c1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: AYXFVSAODMCRBM-NSCUHMNNSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 321 nM (pChEMBL 6.489999771118164)
Descriptors: MW 570.64, ALogP 5.2, HBA 7, HBD 2, PSA 128.17, QED 0.28
Compound (SMILES): Cc1nn(C)cc1-c1cc(C(=O)Nc2c(Cl)ccc(NS(=O)(=O)c3ccccc3F)c2F)c2ncnc(N)c2c1
InChIKey: SLZQHMNLJFHHQH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of of human recombinant His6-tagged B-Raf V600E mutant expressed in baculovirus infected cells co-expresing CDC37 in presence of [gamma33P]ATP incubated for 60 mins by scintillation counting method
Measurement: Ki <= 0.08 nM (pChEMBL 10.097000122070312)
Descriptors: MW 584.01, ALogP 4.91, HBA 8, HBD 3, PSA 144.89, QED 0.26
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Binding affinity to human STK17A assessed as displacement of immobilized ligand by KINOMEscan scanMAX assay relative to control
Measurement: Kd = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): N#Cc1c(-c2ccc(Cl)cc2)cn(-c2ccc(S(N)(=O)=O)cc2)c1N
InChIKey: YTUJINOQEQGXDS-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 2874.1 nM (pChEMBL 5.539999961853027)
Descriptors: MW 372.84, ALogP 2.9, HBA 5, HBD 2, PSA 114.9, QED 0.73
Compound (SMILES): CC(F)(F)CN1CCC(C(=O)Nc2cc3cc(-c4cnco4)cnc3cn2)CC1
InChIKey: ISPDXUPFMBCITB-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 401.42, ALogP 3.59, HBA 6, HBD 1, PSA 84.15, QED 0.7
Compound (SMILES): Cl.Oc1ccccc1C1NCCc2c1[nH]c1ccc(Cl)cc21
InChIKey: GWTYJHNSTXGCFP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 298.77, ALogP 3.76, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): O=[N+]([O-])c1ccc(N/C(Cc2ccc(Cl)cc2)=N\O)c2nonc12
InChIKey: BIUHMRRXHQWMMV-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO assessed as N-formylkynurenine formation using L-tryptophan as substrate measured after 1 hrs by UV-vis spectrophotometric analysis
Measurement: IC50 = 51000 nM (pChEMBL 4.289999961853027)
Descriptors: MW 347.72, ALogP 3.23, HBA 7, HBD 2, PSA 126.68, QED 0.24
Compound (SMILES): C[C@H](NC(=O)Cn1nc2ccc(F)cn2c1=O)c1ccc(Cl)cc1
InChIKey: XRQVUYUOHKCIFR-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 348.76, ALogP 2.17, HBA 5, HBD 1, PSA 68.4, QED 0.79
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OC(C)c1ccccc1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: KDJLBNOAIJYONY-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 426.49, ALogP 5.23, HBA 4, HBD 0, PSA 40.8, QED 0.42
Compound (SMILES): CCCCNNC(=O)c1cccnc1
InChIKey: NBKPFBBNYBOQPN-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 = 4347 nM (pChEMBL 5.360000133514404)
Descriptors: MW 193.25, ALogP 1.12, HBA 3, HBD 2, PSA 54.02, QED 0.54
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(OC)ncnc4C4CC4)nc3n([C@H](C)C3CC3)c2=O)nc1
InChIKey: LYWORTORILMZIS-OAHLLOKOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human PBMC assessed as reduction in anti-CD3/IL-23 stimulated IL-17 level measured after 3 days by MSD assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 562.66, ALogP 3.3, HBA 12, HBD 1, PSA 154.74, QED 0.3
Compound (SMILES): CNc1ccnn2c(=O)n(CC(=O)N[C@@H](C)c3ccc(OC(F)(F)F)cc3)nc12
InChIKey: CRLCKMXHMPDGCP-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 410.36, ALogP 1.71, HBA 8, HBD 2, PSA 102.55, QED 0.64
Compound (SMILES): O=C(c1ccc(Cl)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(F)c2)CC1
InChIKey: WQLAYHBUUKJKQO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): Cc1ccc(Nc2cc(N3CCNCC3)nc3ccnn23)c(C)c1
InChIKey: UGVYSHQCGDCJPR-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 322.42, ALogP 2.5, HBA 6, HBD 2, PSA 57.49, QED 0.78
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCCC(NS(C)(=O)=O)C3)cc2)nc2sccc12
InChIKey: WVWGTOGGUMSNSD-GQCTYLIASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y188L mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 16170 nM (pChEMBL 4.789999961853027)
Descriptors: MW 574.73, ALogP 5.9, HBA 9, HBD 2, PSA 120.24, QED 0.25
Compound (SMILES): CC(C)N(CCCN1CCN(c2cccc(Cl)c2Cl)CC1)C(=O)c1ccccc1
InChIKey: HELWYWUXDYKBMW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in CHO-K1 cells measured after 15 mins by FLIPR assay
Measurement: IC50 = 2008 nM (pChEMBL 5.699999809265137)
Descriptors: MW 434.41, ALogP 5.06, HBA 3, HBD 0, PSA 26.79, QED 0.61
Compound (SMILES): CCCC#Cc1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: UQVZHAXDYLQVSK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 361 nM (pChEMBL 6.440000057220459)
Descriptors: MW 596.68, ALogP 5.31, HBA 7, HBD 2, PSA 128.17, QED 0.25
Compound (SMILES): O=c1[nH]ncc(N2CCc3c(ncnc3Oc3ccc(F)cc3C(F)(F)F)C2)c1Cl
InChIKey: IQFZADSTVFSHDX-UHFFFAOYSA-N
Target: Short transient receptor potential channel 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13507
Assay: Inhibition of TRPC3 (unknown origin) expressed in HEK293 cells assessed as reduction in OAG stimulated Ca2+ influx by FLIPR assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 441.77, ALogP 3.73, HBA 6, HBD 1, PSA 84, QED 0.62
Compound (SMILES): Cc1cc(/C=N/O)c(O)c(CNc2ccc(Cn3cncn3)cc2)c1
InChIKey: MSTUXHHGHKBRJQ-LSFURLLWSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Reactivation of parathion-inhibited human AChE assessed as dissociation constant incubated for 30 mins by Ellman's method
Measurement: Kd = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 337.38, ALogP 2.76, HBA 7, HBD 3, PSA 95.56, QED 0.37
Compound (SMILES): Cc1cc(C(=O)NS(C)(=O)=O)nc(N2CCC(COc3ccccc3C(F)(F)F)C2)n1
InChIKey: DBIWVUQOUFOQDI-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Displacement of FITC-diclofenac from human plasma derived TTR measured after overnight incubation by fluorescence polarization assay
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 458.46, ALogP 2.4, HBA 7, HBD 1, PSA 101.49, QED 0.71
Compound (SMILES): COc1ccc(-c2cnc3c(c2)C=CS(=O)(=O)O3)cc1
InChIKey: PXHUYCWEZYIHHP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 86.8 nM (pChEMBL 7.059999942779541)
Descriptors: MW 289.31, ALogP 2.45, HBA 5, HBD 0, PSA 65.49, QED 0.79
Compound (SMILES): Cc1ncc(-c2ccc3cnc(NC(=O)C4(F)CC4)cc3c2)n1C
InChIKey: JDBSMBPIDCBURU-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 678 nM (pChEMBL 6.170000076293945)
Descriptors: MW 324.36, ALogP 3.38, HBA 4, HBD 1, PSA 59.81, QED 0.8
Compound (SMILES): CC1(C)Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)(F)F
InChIKey: QIMVRHMVKAJIDE-QHCPKHFHSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: MCF-7 ER Down-Regulation Assay: The ability of compounds to down-regulate Estrogen Receptor (ER) numbers was assessed in a cell based immuno-fluorescence assay using the MCF-7 human ductal carcinoma breast cell line. MCF-7 cells were revived directly from a cryovial (approx 5×106 cells) in Assay Medium (phenol red free Dulbecco's Modified Eagle's medium (DMEM); Sigma D5921) containing 2 mM L-Glutamine and 5% (v/v) Charcoal/Dextran treated foetal calf serum. Cells were syringed once using a sterile 18G×1.5 inch (1.2×40 mm) broad gauge needle and cell density was measured using a Coulter Counter (Beckman). Cells were further diluted in Assay Medium to a density of 3.75×104 cells per mL and 40 μL per well added to transparent bottomed, black, tissue culture-treated 384 well plates (Costar, No. 3712) using a Thermo Scientific Matrix WellMate or Thermo Multidrop. Following cell seeding, plates were incubated overnight at 37° C., 5% CO2 (Liconic carousel incubator). Test data was generated using the LabCyte Echo model 555 compound reformatter which is part of an automated workcell (Integrated Echo 2 workcell). Compound stock solutions (10 mM) of the test compounds were used to generate a 384 well compound dosing plate (Labcyte P-05525-CV1). 40 μL of each of the 10 mM compound stock solutions was dispensed into the first quadrant well and then 1:100 step-wise serial dilutions in DMSO were performed using a Hydra II (MATRIX UK) liquid handling unit to give 40 μL of diluted compound into quadrant wells 2 (0.1 mM), 3 (1 μM) and 4 (0.01 μM), respectively. 40 μL of DMSO added to wells in row P on the source plate allowed for DMSO normalisation across the dose range. To dose the control wells 40 μL of DMSO was added to row O1 and 40 μL of 100 μM fulvestrant in DMSO was added to row O3 on the compound source plate.
Measurement: IC50 = 0.51 nM (pChEMBL 9.289999961853027)
Descriptors: MW 490.55, ALogP 4.7, HBA 5, HBD 2, PSA 60.08, QED 0.47
Compound (SMILES): CC(=O)Nc1ccc(OCCCN2CCN(c3cccc(C(F)(F)F)c3)CC2)cc1
InChIKey: KJSFNQGLVXQNCV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to 5HT2A receptor (unknown origin)
Measurement: Ki = 447.9 nM (pChEMBL 6.349999904632568)
Descriptors: MW 421.46, ALogP 4.25, HBA 4, HBD 1, PSA 44.81, QED 0.68
Compound (SMILES): O=C(NC1CC2CCC(C1)N2Cc1cccc(Br)c1)c1ccc2ccccc2c1
InChIKey: CVNMEGDKYDEZEZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserin from rat cerebral cortex 5HT2A receptor measured after 20 mins by liquid scintillation counter method
Measurement: Ki = 571 nM (pChEMBL 6.239999771118164)
Descriptors: MW 449.39, ALogP 5.53, HBA 2, HBD 1, PSA 32.34, QED 0.57
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CC(O)C4COC4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: RRBVMNSPISLWHJ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 4873 nM (pChEMBL 5.309999942779541)
Descriptors: MW 640.69, ALogP 3.52, HBA 9, HBD 3, PSA 157.63, QED 0.23
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1ccc(Cl)cc1
InChIKey: JTDCOWMSDVDUOO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 3311.31 nM (pChEMBL 5.480000019073486)
Descriptors: MW 314.82, ALogP 4.12, HBA 2, HBD 1, PSA 32.34, QED 0.92
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2c1CCO2
InChIKey: WGICPLUIQIXVNT-XQKZEKTMSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 2344.23 nM (pChEMBL 5.630000114440918)
Descriptors: MW 251.3, ALogP 2.03, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(C(=O)N2CCCC(Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)C2)c1
InChIKey: CXCNOMPSSIJKDE-XYOKQWHBSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 177 nM (pChEMBL 6.75)
Descriptors: MW 582.8, ALogP 5.49, HBA 9, HBD 2, PSA 103.6, QED 0.24
Compound (SMILES): COC1CCN(c2ccn3c(=O)n(CC(=O)N[C@@H](C)c4ccc(OC(F)(F)F)cc4)nc3c2)CC1
InChIKey: ODCLSKIDUGQAKZ-HNNXBMFYSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 >= 100 nM (pChEMBL 7)
Descriptors: MW 493.49, ALogP 2.89, HBA 8, HBD 1, PSA 90.1, QED 0.54
Compound (SMILES): N#Cc1cc(-c2c(O)cc(C(=O)c3ccccc3)cc2O)ccc1F
InChIKey: NZLCRGDLEDOHCD-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human recombinant cannabinoid CB2 receptor expressed in HEK cells transfected with CNG assessed as increase in cAMP level measured up to 1 hr by ACTOne membrane potential dye based assay
Measurement: EC50 = 2818.38 nM (pChEMBL 5.550000190734863)
Descriptors: MW 333.32, ALogP 4.01, HBA 4, HBD 2, PSA 81.32, QED 0.71
Compound (SMILES): C[C@H]1OC2(CCN(CCc3ccccc3)CC2)CN(C)C1=O
InChIKey: QEHPEXFTPOUOLB-OAHLLOKOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 319 nM (pChEMBL 6.5)
Descriptors: MW 302.42, ALogP 1.94, HBA 3, HBD 0, PSA 32.78, QED 0.86
Compound (SMILES): O=C(N[C@@H](CCCCNC(=O)c1ccccc1O)c1ncc(-c2ccc3ccccc3c2)[nH]1)c1cncs1
InChIKey: NIXOIBDALBDEAM-QHCPKHFHSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 525.63, ALogP 5.46, HBA 6, HBD 4, PSA 120, QED 0.18
Compound (SMILES): FC(F)(F)c1cc2cc(c1)Nc1nc(nc(-c3cccc(C(F)(F)F)n3)n1)NCC/C=C/C2
InChIKey: BKGGRLHHYHPJIQ-OWOJBTEDSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of wild type IDH2 (unknown origin) assessed as reduction in NADPH production using sodium(D)-isocitrate and NADP as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 466.39, ALogP 5.63, HBA 6, HBD 2, PSA 75.62, QED 0.36
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccnc(N3CCOCC3)c2F)[nH]1
InChIKey: HWZMSMSAVMLYQH-RPWUZVMVSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by traditional preparative HPLC work-flow
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 554.71, ALogP 4.27, HBA 7, HBD 2, PSA 103.45, QED 0.38
Compound (SMILES): O=[N+]([O-])/C(Cl)=C/c1ccc([N+](=O)[O-])cc1
InChIKey: YVKSKDUKJHYERJ-VMPITWQZSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human FBPase S124A mutant
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 228.59, ALogP 2.41, HBA 4, HBD 0, PSA 86.28, QED 0.45
Compound (SMILES): NC[C@@H](C(=O)Nc1ccc2cnccc2c1)c1ccc(CO)cc1
InChIKey: LTXBFJFJUIJOQE-GOSISDBHSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: In Vitro Effect Assay: Table 2: Inhibitory effect of each compound synthesized above on Rho-associated protein kinase (ROCK) was tested.Method 1. 10 mM test compound was diluted to 1 mM with DMSO, and then further diluted to 300 nM. Netarsudil (AR-13324) is a commercial drug for decreasing intraocular pressure, and AR-13503 is an active metabolite of AR-13324. 2. The 300 nM test compound mentioned above was serially diluted to obtain test compounds with concentrations of 100 nM, 33 nM, 11 nM, 3.7 nM, 1.2 nM and 0.4 nM, respectively. 3. 1 μL of the serially diluted test compound mentioned above was added to 49 μL of the modified ROCK reaction buffer (0.05 M Trizma® hydrochloride buffer (pH 7.5) containing 0.1 M KCl, 0.01 M MgCl2, 0.1 mM EGTA and 2.25 μg/mL ROCK1) to obtain an experimental group sample. 1 μL of DMSO was taken to add to 49 μL of an adjusted ROCK reaction buffer to obtain a positive control group sample (maximum value=100%). 1 μL of DMSO was taken to add to 49 μL of a buffer (0.05 M Trizma® hydrochloride buffer (pH 7.5) containing 0.1 M KCl, 0.01 M MgCl2 and 0.1 mM EGTA) to obtain a vehicle control group sample (minimum value=0%). 4. 20 μL of the above prepared sample was added to a flat-bottomed 96-well plate, and 20 μL ROCK ATP buffer was added to each well. 5. The 96-well plate mentioned above was placed on an orbital shaker and reacted at room temperature for 90 minutes.6. Next, 40 μL of Kinase-Glo luminescent kinase assay solution (Promega, RV6712) was added to the 96-well plate mentioned above, and the 96-well plate was placed on an orbital shaker and reacted at room temperature for 10 minutes. 7. The luminescence value of each well of the 96-well plate was determined by SpectraMax M5 microplate reader, and the ROCK inhibition rate (%) was calculated by the following formula.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 321.38, ALogP 2.41, HBA 4, HBD 3, PSA 88.24, QED 0.67
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(C)cn2)C1
InChIKey: NDQRCUOYOAPFLR-DLBZAZTESA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MV4-11 cells assessed as induction of caspase-3/7 activation measured after 6 hrs followed by Caspase-glo reagent based assay
Measurement: EC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 409.53, ALogP 3.47, HBA 5, HBD 2, PSA 88.91, QED 0.81
Compound (SMILES): Cc1cc(C(=O)Nc2c(Cl)ccc(NS(=O)(=O)c3cc(F)ccc3F)c2F)c2ncnc(N[C@H]3CC[C@H](N)CC3)c2c1.Cl
InChIKey: VUEVDUBSSBJDSP-BHQIMSFRSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of of human recombinant His6-tagged B-Raf V600E mutant expressed in baculovirus infected cells co-expresing CDC37 in presence of [gamma33P]ATP incubated for 60 mins by scintillation counting method
Measurement: Ki = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 619.07, ALogP 5.74, HBA 7, HBD 4, PSA 139.1, QED 0.21
Compound (SMILES): COc1ccn(-c2ccc(F)cc2)c(=O)c1C(=O)Nc1ccc(Oc2ccnc(N)c2Cl)c(F)c1
InChIKey: XHIQDQUOOKVPRP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Inhibition of Tyro3 (unknown origin)
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 498.87, ALogP 4.8, HBA 7, HBD 2, PSA 108.47, QED 0.4
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3c[nH]c4ccccc34)oc12
InChIKey: LESNIKLFCUWFHE-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethoxyresorufin as substrate after 50 mins in presence of NADP+ by EROD assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 401.42, ALogP 5.12, HBA 5, HBD 1, PSA 73.69, QED 0.42
Compound (SMILES): O=S(=O)(N[C@H]1CCN(CCCc2noc3ccccc23)C1)c1cc2ccccc2o1
InChIKey: FHTQWEHAVYFMHP-KRWDZBQOSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from recombinant human 5HT7 receptor expressed in CHOK1 cell membranes measured after 120 mins by microbeta counting method
Measurement: Ki = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 425.51, ALogP 3.56, HBA 6, HBD 1, PSA 88.58, QED 0.49
Compound (SMILES): FC(F)(F)c1cc2cc(c1)Nc1nc(nc(-c3cccc(C(F)(F)F)n3)n1)NCCCCCC2
InChIKey: UTJJIEVWKZKWEI-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of wild type IDH2 (unknown origin) assessed as reduction in NADPH production using sodium(D)-isocitrate and NADP as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 482.43, ALogP 6.24, HBA 6, HBD 2, PSA 75.62, QED 0.4
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@@H]1CCOC[C@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: WTHILFAMRXZBRN-SKBVVQJISA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): O=C(N[C@@H](CCCCNC(=O)c1c(O)cccc1F)c1ncc(-c2ccc3ccccc3c2)[nH]1)c1cncs1
InChIKey: BBLOAIWXSMVTHJ-QFIPXVFZSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 543.62, ALogP 5.6, HBA 6, HBD 4, PSA 120, QED 0.17
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3ccc(Br)cn3)oc12
InChIKey: IDDUSDOHMRMLKJ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethoxyresorufin as substrate after 50 mins in presence of NADP+ by EROD assay
Measurement: IC50 = 622.8 nM (pChEMBL 6.210000038146973)
Descriptors: MW 442.26, ALogP 4.8, HBA 6, HBD 0, PSA 70.79, QED 0.42
Compound (SMILES): O=C(Nc1cncc(-c2cc3c(-c4cc5c(-c6cccc(F)c6)ccnc5[nH]4)n[nH]c3cn2)c1)C1CC1
InChIKey: LOQYMTXWNTWVBJ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.51, ALogP 5.72, HBA 5, HBD 3, PSA 112.24, QED 0.29
Compound (SMILES): Cc1ccc(-c2c(-c3ccc(C#N)cc3)nc(N3CCC(N)CC3)n(C)c2=O)cc1
InChIKey: KFFPAIUTQJYMTC-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: In Vitro Enzyme Inhibition Assay: This assay determines the ability of a test compound to inhibit LSD1 demethylase activity. E. coli expressed full-length human LSD1 (Accession number O60341) was purchased from Active Motif (Cat#31334).The enzymatic assay of LSD1 activity is based on Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The inhibitory properties of compounds to LSD1 were determined in 384-well plate format under the following reaction conditions: 0.1-0.5 nM LSD1, 50 nM H3K4me1-biotin labeled peptide (Anaspec cat #64355), 2 μM FAD in assay buffer of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified histone H3 lysine 4 (H3K4) antibody (PerkinElmer) in the presence of LSD1 inhibitor such as 1.8 mM of Tranylcypromine hydrochloride (2-PCPA) in LANCE detection buffer (PerkinElmer) to final concentration of 12.5 nM and 0.25 nM respectively.The assay reaction was performed according to the following procedure: 2 μL of the mixture of 150 nM H3K4me1-biotin labeled peptide with 2 μL of 11-point serial diluted test compound in 3% DMSO were added to each well of plate, followed by the addition of 2 μL of 0.3 nM LSD1 and 6 μM of FAD to initiate the reaction. The reaction mixture was then incubated at room temperature for one hour, and terminated by the addition of 6 μL of 1.8 mM 2-PCPA in LANCE detection buffer containing 25 nM Phycolink Streptavidin-allophycocyanin and 0.5 nM Europium-anti-unmodified H3K4 antibody. Enzymatic reaction is terminated within 15 minutes if 0.5 LSD1 enzyme is used in the plate. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 399.5, ALogP 3.22, HBA 6, HBD 1, PSA 87.94, QED 0.73
Compound (SMILES): CNC(=O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: WYAWDSRKUQMPMM-OAQYLSRUSA-N
Target: Signal transducer and activator of transcription 1 (SINGLE PROTEIN), Mus musculus
UniProt: P42225
Assay: Inhibition of oligonucleotide [32P]-labelled 5'-AGCITCATTTCCCGTAAATCCCTA probe binding to STAT1 homodimer in mouse NIH3T3 nuclear extract preincubated for 30 mins followed by hSIE probe addition by EMSA analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 652.64, ALogP 4.89, HBA 6, HBD 2, PSA 119.91, QED 0.2
Compound (SMILES): O=C1CCc2cccc(c2)-c2cncc3[nH]c(nc23)-c2n[nH]c3ccc(cc23)-c2cncc(c2)N1
InChIKey: PPVASYJRWJUURU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRK1A kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission.Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 457.5, ALogP 5.11, HBA 5, HBD 3, PSA 112.24, QED 0.29
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCC1CCN(Cc2ccccc2F)CC1
InChIKey: BDUXOMBAFKYZLK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate incubated for 10 mins by Ellman's method
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 523.63, ALogP 4.34, HBA 7, HBD 2, PSA 96.45, QED 0.43
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3cnc4[nH]nc(-c5cc6c(-c7ccncc7)cccc6[nH]5)c4c3)c2)C1
InChIKey: JSTXQPFSEIMDRP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 895 nM (pChEMBL 6.050000190734863)
Descriptors: MW 507.55, ALogP 6.07, HBA 5, HBD 2, PSA 86.38, QED 0.3
Compound (SMILES): CC(C)n1cc(-c2nc(Nc3ccc4c(c3)CCN(CCCO)C4)ncc2F)cn1
InChIKey: YYJCAOKDRHIHHY-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 453 nM (pChEMBL 6.340000152587891)
Descriptors: MW 410.5, ALogP 3.54, HBA 7, HBD 2, PSA 79.1, QED 0.62
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)CN(Cc2ccccc2)C1=O
InChIKey: YCLJTMLYPHXJPM-NETOACFBSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse MC3R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 949.13, ALogP -0.84, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): Cc1nnc(-c2nc(C)n3ccc(Nc4nccc(-c5cc(CN(C)C)n(C)n5)n4)cc23)o1
InChIKey: PAZNLQHSWVMGIW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ZAP-70 (SINGLE PROTEIN), Homo sapiens
UniProt: P43403
Assay: Binding affinity to ZAP70 (unknown origin)
Measurement: Kd = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 444.5, ALogP 3, HBA 11, HBD 1, PSA 115.09, QED 0.42
Compound (SMILES): CC(C)Oc1cc(F)cc2c(N3CCN(c4ccccc4F)CC3)c(C#N)cnc12
InChIKey: URGDPHSQVLSJCM-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Positive allosteric modulation of rat mGlu7 expressed in HEK293 cells co- expressing GIRK assessed as potentiation of L-AP4-induced thallium flux incubated for 140 sec by FluoZin2-AM dye based fluorescence analysis
Measurement: EC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 408.45, ALogP 4.5, HBA 5, HBD 0, PSA 52.39, QED 0.64
Compound (SMILES): CN1CCN(CCOc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc2NC(=O)c2cc([N+](=O)[O-])ccc2F)CC1
InChIKey: LGMORXNEVKAZOM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST tagged EGFR (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 598.01, ALogP 5.09, HBA 9, HBD 2, PSA 125.76, QED 0.2
Compound (SMILES): C[C@H](CO)n1cnnc1-c1cccc(NC(=O)Nc2ccc3ccccc3n2)n1
InChIKey: PBCNGKYVBNFZMC-CYBMUJFWSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of TAK1 (unknown origin)
Measurement: IC50 = 1883 nM (pChEMBL 5.71999979019165)
Descriptors: MW 389.42, ALogP 3.09, HBA 7, HBD 3, PSA 117.85, QED 0.48
Compound (SMILES): CC(C)(C)C#CCOC(=O)N[C@@H]1CCN(C(=O)N[C@@H](C(=O)N2CCC[C@H]2c2nc(-c3ccc([C@H]4CC[C@H](NC(=O)c5cnc(CO)cn5)CC4)cc3)c[nH]2)c2ccccc2)C1
InChIKey: PPZFNMYHDWJYEL-SRFGQFSHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of Hepatitis C virus 2a NS5A
Measurement: EC50 < 0.01 nM (pChEMBL 11)
Descriptors: MW 830, ALogP 5.78, HBA 9, HBD 5, PSA 194.77, QED 0.12
Compound (SMILES): O=C(Nc1cncc(-c2cc3c(-c4cc5c(-c6ccc(F)cc6)nccc5[nH]4)n[nH]c3cn2)c1)C1CC1
InChIKey: KGAGNKDOKCTELT-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 202 nM (pChEMBL 6.699999809265137)
Descriptors: MW 489.51, ALogP 5.72, HBA 5, HBD 3, PSA 112.24, QED 0.29
Compound (SMILES): Cc1ccc(S(=O)(=O)CC(=O)c2cc3cc(Br)ccc3oc2=O)cc1
InChIKey: IGBCIXWILZRNTH-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 6 hrs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 87.2 nM (pChEMBL 7.059999942779541)
Descriptors: MW 421.27, ALogP 3.52, HBA 5, HBD 0, PSA 81.42, QED 0.48
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@@H]2COP(=O)(O)O[C@H]3C[C@H](n4cnc5c(O)ncnc54)O[C@@H]3COP(=O)(O)O[C@H]2[C@H]1F
InChIKey: WAIOAMRVKJBOSB-JMMIKBGYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of STING in human THP-1-Dual cells assessed as induction of type I IFNs by measuring stimulation of NF-kappaB pathway incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 25500 nM (pChEMBL 4.590000152587891)
Descriptors: MW 645.39, ALogP 0.49, HBA 18, HBD 4, PSA 263.43, QED 0.22
Compound (SMILES): CN1CC[C@H](CNC(=O)c2cc(-n3cc(NC(=O)Nc4ccccc4Cl)cn3)cs2)C1
InChIKey: ZILWEQNTUQYRDZ-CQSZACIVSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3alpha1 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 222 nM (pChEMBL 6.650000095367432)
Descriptors: MW 458.98, ALogP 3.91, HBA 6, HBD 3, PSA 91.29, QED 0.52
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N)nc(N)nc32)[C@H](O)[C@@H]1O
InChIKey: CYXIZIBYQPGCAB-QMWPFBOUSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Kd > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 323.31, ALogP -2.25, HBA 10, HBD 5, PSA 174.43, QED 0.42
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)C4)c(Cl)cn2)C1
InChIKey: KZJSUGHOGMRTFQ-JQXSQYPDSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MCF7 cells assessed as reduction in RNA Polymerase 2 CTD phosphorylation at Ser2 residues measured after 6 hrs by immunofluorescence assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 415.93, ALogP 3.42, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): c1cnc2c(Nc3ccc4c(C5CC5)nccc4c3)n[nH]c2c1
InChIKey: SUGNFYVNOSXJEL-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Metabotropic Glutamate Receptor Activity: The disclosed compounds and compositions can be evaluated for their ability to act as a potentiator of metabotropic glutamate receptor activity, in particular mGluR4 activity, by any suitable known methodology known in the art. For example, Chinese Hamster Ovary (CHO) cells transfected with human mGluR4 or HEK cells co-transfected with rat mGluR4 and the G-protein regulated Inwardly Rectifying Potassium channel (GIRK) were plated in clear bottom assay plates for assay in a Hamamatsu FDSS Fluorometric Plate Reader. The cells were loaded with either a Ca2+-sensitive fluorescent dye or the thallium responsive dye and the plates were washed and placed into a suitable kinetic plate reader. For human mGluR4 assays, a fluorescence baseline was established for 3-5 seconds, the disclosed compounds were then added to the cells, and the response in cells was measured. Approximately two and a half minutes later, a concentration of mGluR4 orthosteric agonist (e.g. glutamate or L-AP4) eliciting approximately 20% (EC20) of the maximal agonist response was added to the cells, and the response was measured. Two minutes later, a concentration of mGluR4 agonist (e.g. glutamate or L-AP4) eliciting 80% (EC80) of the maximal agonist response was added to the cells, and the response was measured. For rat mGluR4/GIRK experiments, a baseline was established for approximately five seconds, disclosed compounds were added, and either an EC20 or EC80 concentration of agonist was added approximately two and one half minutes later. Potentiation of the agonist response of mGluR4 by the disclosed compounds was observed as an increase in response to the EC20 concentration of agonist in the presence of compound compared to the response to agonist in the absence of compound. Similarly, antagonism of the agonist response of mGluR4 by the disclosed compounds was observed as a decrease in response to the EC80 concentration of agonist in the presence of compound compared to the response to agonist in the absence of compound.
Measurement: EC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 301.35, ALogP 4.13, HBA 4, HBD 2, PSA 66.49, QED 0.6
Compound (SMILES): COC(=O)c1cnc(Nc2cnc(C#N)cn2)cc1NC1C[C@H]2CC[C@@H](C1)N2C
InChIKey: HUAGSKZSJRBBRA-LQDVMPOASA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of CHK1 in human HT-29 cells assessed as abrogation of etoposide-induced G2 checkpoint arrest by ELISA
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 393.45, ALogP 2.31, HBA 9, HBD 2, PSA 116.06, QED 0.74
Compound (SMILES): NNc1ncnc2c1c(-c1ccc(Cl)cc1)cn2-c1ccc(S(N)(=O)=O)cc1
InChIKey: GJFYUNZYSZQCNC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 85.6 nM (pChEMBL 7.070000171661377)
Descriptors: MW 414.88, ALogP 2.67, HBA 7, HBD 3, PSA 128.92, QED 0.35
Compound (SMILES): O=C(Nc1cnn(-c2csc(C(=O)N[C@@H]3CCOC3)c2)c1)Nc1ccccc1Cl
InChIKey: NDXBTYNWEFNKOR-GFCCVEGCSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 431.91, ALogP 3.75, HBA 6, HBD 3, PSA 97.28, QED 0.57
Compound (SMILES): N#Cc1ccc(-c2ccc(Cc3nc(C(=O)NCC(=O)N4CC(F)(F)C[C@H]4C#N)cs3)cc2)cc1
InChIKey: YEVNJKBZDRFUJQ-FQEVSTJZSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of PREP (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 491.52, ALogP 3.76, HBA 6, HBD 1, PSA 109.88, QED 0.56
Compound (SMILES): Oc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6cccc(F)c6)cncc5[nH]4)c3n2)c1
InChIKey: ZADWYQQTLUNDSU-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 423.41, ALogP 4.47, HBA 6, HBD 3, PSA 116.26, QED 0.39
Compound (SMILES): CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)NCc1cccc(OC)c1
InChIKey: UTIZQJLALOGMDO-ZKWNWVNESA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human sEH expressed in baculovirus expression system using MNPC as substrate by fluorescence-based assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 423.64, ALogP 7.46, HBA 2, HBD 1, PSA 38.33, QED 0.21
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccn2)CC1
InChIKey: ZMEGJWWPDKBOER-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation levels incubated for 15 mins by Alphalisa assay
Measurement: EC50 = 0.4266 nM (pChEMBL 9.369999885559082)
Descriptors: MW 409.86, ALogP 3.49, HBA 4, HBD 1, PSA 54.46, QED 0.71
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2sc(CN3CCN(C4CCCC4)CC3=O)cc2n1
InChIKey: CJOAMQSARNBSBT-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)
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 545.71, ALogP 4.02, HBA 9, HBD 0, PSA 79.62, QED 0.36
Compound (SMILES): NC(=O)c1sc(-c2ccnc(NC(=O)CNCCNc3c4c(nc5ccccc35)CCCC4)c2)nc1OCC1CC1
InChIKey: FOAOMODSQTYPSH-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human N-terminal His6-tagged GSK-3beta H350L mutant expressed in baculovirus infected Sf21 cells using GSM as substrate incubated for 30 mins in presence of ATP by kinase-glo luminescence assay
Measurement: IC50 = 42.6 nM (pChEMBL 7.369999885559082)
Descriptors: MW 571.71, ALogP 4.16, HBA 9, HBD 4, PSA 144.15, QED 0.19
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCCC(Nc3ncc(/C=C/c4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: BLUORUUGUNHQIW-OUKQBFOZSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 505.64, ALogP 5.44, HBA 7, HBD 2, PSA 100.36, QED 0.41
Compound (SMILES): CC(C)(C)/C=C/c1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: GOLPRMYLOHXAMC-ZHACJKMWSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 612.72, ALogP 6.22, HBA 7, HBD 2, PSA 128.17, QED 0.23
Compound (SMILES): CC(=O)N1CCC(C(=O)N2C[C@@H](c3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)[C@@](C)(c3ccccc3)C2)CC1
InChIKey: YXYVNJXYQMACDG-UKILVPOCSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 556.55, ALogP 5.14, HBA 3, HBD 1, PSA 60.85, QED 0.53
Compound (SMILES): CCOc1ccc(Nc2n[nH]c(NC(=O)c3ccccc3)n2)cc1
InChIKey: HPQVPAPOFNYTQJ-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human coagulation factor XIIA using Boc-Gln-Gly-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 323.36, ALogP 3.2, HBA 5, HBD 3, PSA 91.93, QED 0.65
Compound (SMILES): CCNCc1cncc(-c2ccc3[nH]nc(-c4cc5cnccc5[nH]4)c3c2)c1
InChIKey: URHQFIKNWRKBRG-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 368.44, ALogP 4.28, HBA 4, HBD 3, PSA 82.28, QED 0.43
Compound (SMILES): Cc1ccc(C#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)c2)s1
InChIKey: LZIKVHXLVMNROK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 367 nM (pChEMBL 6.429999828338623)
Descriptors: MW 632.76, ALogP 5.79, HBA 8, HBD 2, PSA 128.17, QED 0.21
Compound (SMILES): CC(C)C(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6ccccc6F)cncc5[nH]4)c3n2)c1
InChIKey: QRSOGBZSEGOUSD-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 9838 nM (pChEMBL 5.010000228881836)
Descriptors: MW 492.52, ALogP 5.36, HBA 6, HBD 3, PSA 125.13, QED 0.3
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccc4Cl)CC3)cc2C1=O
InChIKey: QIMOBLHMKZLPIE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]ketanserin from rat cerebral cortex 5HT2A receptor measured after 15 mins by liquid scintillation counting method
Measurement: Ki = 179.3 nM (pChEMBL 6.75)
Descriptors: MW 413.95, ALogP 3.56, HBA 4, HBD 0, PSA 36.02, QED 0.68