lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
Compound (SMILES): Cc1cc2cc(NS(=O)(=O)c3ccc(C(=O)NO)cc3)ccc2n(C)c1=O
InChIKey: AXJXDWNCHLEVAZ-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to BRPF1 (unknown origin) by Isothermal titration calorimetry
Measurement: Kd = 175.2 nM (pChEMBL 6.760000228881836)
Descriptors: MW 387.42, ALogP 1.77, HBA 6, HBD 3, PSA 117.5, QED 0.47
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCNc2ccccc2)CC1
InChIKey: BZPOPHHMWUCUHD-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 inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 186.21 nM (pChEMBL 6.730000019073486)
Descriptors: MW 407.89, ALogP 4.13, HBA 3, HBD 2, PSA 44.37, QED 0.68
Compound (SMILES): CCCCCNNC(=O)c1ccc(CNC(=O)/C=C/c2ccccc2)cc1
InChIKey: BQTCOFJJIMMRQO-NTCAYCPXSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of C-terminal His-tagged recombinant human HDAC2 expressed in Sf9 cells pre-incubated for 2 hrs before acetylated lysine-aminomethyl coumarin-BOC addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 99.56 nM (pChEMBL 7)
Descriptors: MW 365.48, ALogP 3.44, HBA 3, HBD 3, PSA 70.23, QED 0.34
Compound (SMILES): C/C(=N\NC(=O)c1ccc(S(N)(=O)=O)cc1)c1sc2nc3ccccc3n2c1C
InChIKey: FVERZUZFBSEEAW-SSDVNMTOSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 13.7 nM (pChEMBL 7.860000133514404)
Descriptors: MW 427.51, ALogP 2.66, HBA 7, HBD 2, PSA 118.92, QED 0.38
Compound (SMILES): N#Cc1ccc(Nc2nccc([C@H](O)c3ccc(-c4ccc(C#N)cc4)cc3Cl)n2)cc1
InChIKey: LRGUYOVPBIAHKP-XMMPIXPASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 205.5 nM (pChEMBL 6.690000057220459)
Descriptors: MW 437.89, ALogP 5.37, HBA 6, HBD 2, PSA 105.62, QED 0.43
Compound (SMILES): NC(=O)c1cc2c(n1CCF)-c1ccncc1OC21CCC1
InChIKey: AFQAFERZBGFZRQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Haspin Kinase Assay: The kinase assay relies on ADP-GloKM biochemical kinase assay (Promega). This is a luminescent kinase assay that measures ADP formed from a kinase reaction. Then ADP is converted into ATP, which is transformed into a light signal by Ultra-Glo Luciferase. The luminescent signal positively correlates with kinase activity. The assay measures the intrinsic ATPase activity (in the absence of peptidic substrate as phosphate acceptor).The enzyme was purchase from Invitrogen (PV5708) as the kinase domain of GST tagged recombinant human proteins.Assay conditions were as indicated by the kit manufacturers with the following adaptations:Assay buffer: 15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.1 mg/ml BGGAssay volume: 20 μlIncubation time and temperature: 60 min at 30° C.Haspin concentration: 20 nMATP concentration: 150 μMTested compound: Serial 1:3 dilutionsFinal DMSO concentration in the assay: 1%Assays were performed in 384-well plates. The final read out was generated using an EnVision plate reader (Perkin-Elmer). Luminescent relative units are normalized against the control activity included for each compound (i.e., 100% Haspin activity, without compound) and the percentage of inhibition is calculated.
Measurement: IC50 = 24.2 nM (pChEMBL 7.619999885559082)
Descriptors: MW 301.32, ALogP 2.39, HBA 4, HBD 1, PSA 70.14, QED 0.95
Compound (SMILES): COc1ccc(C(=O)NO)cc1C(=O)Nc1ccc2c(c1)cc(C)c(=O)n2C
InChIKey: SUIWTHQZBYYCGP-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to BRPF1 (unknown origin) by Isothermal titration calorimetry
Measurement: Kd = 857 nM (pChEMBL 6.070000171661377)
Descriptors: MW 381.39, ALogP 2.23, HBA 6, HBD 3, PSA 109.66, QED 0.47
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccc(F)cc2)cc1
InChIKey: NLPAQCHZGISERZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of N-terminal FLAG-tagged human recombinant mTOR (1362 to end residues) using ULight-4E-BP1 (Thr37/46) peptide as substrate incubated for 1 hr in presence of ATP by Lance Ultra assay
Measurement: IC50 = 1662 nM (pChEMBL 5.78000020980835)
Descriptors: MW 489.54, ALogP 4.69, HBA 7, HBD 3, PSA 118.96, QED 0.37
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain (unknown origin) by HTRF assay based Morrison titration analysis
Measurement: Ki = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
Compound (SMILES): C#CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: PWEDJMTYYMURIC-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 385.43, ALogP 2.53, HBA 5, HBD 2, PSA 87.22, QED 0.67
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: MAEMKRFOORLALZ-YEJMJCSASA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]-neurotensin from human recombinant NTS1 stably expressed in CHO-K1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 0.43 nM (pChEMBL 9.369999885559082)
Descriptors: MW 1394.69
Compound (SMILES): Cl.O=C([C@@H](Cc1cccc(C(F)(F)F)c1)NS(=O)(=O)c1cc(F)c2c(c1)CCNC2)N1CCCC1
InChIKey: ZADKZNVAJGEFLC-ZMBIFBSDSA-N
Target: Bombesin receptor subtype-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32247
Assay: Selectivity interaction (Enzyme panel (ion channels, GPCRs, other targets)) EUB0000196bCl BRS3
Measurement: Ki = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 499.53, ALogP 3, HBA 4, HBD 2, PSA 78.51, QED 0.6
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(C)cc4n3)C2)cc1
InChIKey: YRQZGISKFWGSDA-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Nc1nc2sc(CCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)o3)cc2c(=O)[nH]1
InChIKey: LYDGQYDYRQVOBF-ZDUSSCGKSA-N
Target: Proton-coupled folate transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NT5
Assay: Inhibition of human PCFT expressed in Chinese Hamster MTXRII-OuaR2-4 R2 cells assessed as reduction in cell proliferation after 96 hrs by CellTiter-blue assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 462.48, ALogP 1.77, HBA 8, HBD 5, PSA 188.61, QED 0.26
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1F
InChIKey: NEGIWTYBODMDQN-MHZLTWQESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 509.62, ALogP 6.55, HBA 3, HBD 1, PSA 49.77, QED 0.35
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccccc4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: JDOWDLRLLSFBOY-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 514.61, ALogP 6.74, HBA 6, HBD 1, PSA 76.88, QED 0.28
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@](C)(c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)F
InChIKey: RVVNCNQGXBSLJG-CPJLOUKISA-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 = 0.91 nM (pChEMBL 9.039999961853027)
Descriptors: MW 472.56, ALogP 4.19, HBA 5, HBD 2, PSA 60.08, QED 0.52
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(-c3ccc4ccccc4c3)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: SLPDXDVCXNVEEV-YJLRWSCOSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 8.913 nM (pChEMBL 8.050000190734863)
Descriptors: MW 1150.36
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CC(C)O)C(=O)NCc1ccc(Cl)cc1)c1sccc1C
InChIKey: WLGKWBVRCUZNJF-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 57543.99 nM (pChEMBL 4.239999771118164)
Descriptors: MW 517.16, ALogP 6.29, HBA 5, HBD 2, PSA 52.57, QED 0.31
Compound (SMILES): Cc1c(-c2cnc3[nH]ncc3c2)ccc2c3oc(CN)nc3c(=O)n(C3CC3)c12
InChIKey: WNQBSZMKYWMZEY-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 22800 nM (pChEMBL 4.639999866485596)
Descriptors: MW 386.42, ALogP 3.18, HBA 7, HBD 2, PSA 115.62, QED 0.49
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CCC4CCCC4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: QSEWNTOBSWZCKU-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Binding affinity to human His-tagged LDHA by SPR analysis
Measurement: Kd = 0.1235 nM (pChEMBL 9.90999984741211)
Descriptors: MW 636.75, ALogP 6.09, HBA 7, HBD 2, PSA 128.17, QED 0.21
Compound (SMILES): O=C1NC(=O)c2cc(N(Cc3ccc(C4CCCCC4)cn3)C(=O)[C@H]3CCN3S(=O)(=O)c3c(F)c(F)c(F)c(F)c3F)ccc21
InChIKey: DFAZGBBGEGHQMP-OAQYLSRUSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: In Vitro Assay: Nuclear extract preparations and DNA-binding activity/electrophoretic mobility shift assay (EMSA) were carried out as previously described (Zhang X, et al., (2010) Biochem Pharmacol 79:1398-409; Zhang X, et al., (2012) Proc Natl Acad Sci USA 109:9623-8). The 32P-labeled oligonucleotide probes used were hSIE (high affinity sis-inducible element from the c-fos gene, m67 variant, 5′-AGCTTCATTTCCCGTAAATCCCTA) (SEQ ID NO: 1) that binds Stat1 and Stat3 and MGFe (mammary gland factor element from the bovine β-casein gene promoter, 5′-AGATTTCTAGGAATTCAA) (SEQ ID NO: 2) for Stat1 and Stat5 binding. Except where indicated, nuclear extracts were pre-incubated with compound for 30 min at room temperature prior to incubation with the radiolabeled probe for 30 min at 30° C. before subjecting to EMSA analysis. Where appropriate, bands corresponding to Stat3:DNA complexes were scanned and quantified for each concentration of compound using ImageJ and plotted as percent of control (DMSO) against concentration of compound, from which the IC50 values were derived.
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 648.61, ALogP 4.7, HBA 6, HBD 1, PSA 116.75, QED 0.17
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(C)ncnc4C4CC4)nc3n([C@@H](C)C3CC3)c2=O)nc1
InChIKey: FOJNTKBAAJLZRH-INIZCTEOSA-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 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 546.66, ALogP 3.6, HBA 11, HBD 1, PSA 145.51, QED 0.33
Compound (SMILES): Cn1ccc(NC(=O)CCN2CCCc3ccccc32)n1
InChIKey: FTGSJULYBLEGFY-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 977.24 nM (pChEMBL 6.010000228881836)
Descriptors: MW 284.36, ALogP 2.2, HBA 4, HBD 1, PSA 50.16, QED 0.94
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2ccc3c(c2)C(=O)N(C)CC3)CC1
InChIKey: SLPNWORIUMAUFP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 409.53, ALogP 2.91, HBA 5, HBD 0, PSA 45.25, QED 0.66
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](Cc3c[nH]c4ccccc34)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: FPAJEPLZUWCXEI-PGNOFCDOSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 2.18 nM (pChEMBL 8.65999984741211)
Descriptors: MW 503.6, ALogP 2.97, HBA 6, HBD 4, PSA 107.05, QED 0.41
Compound (SMILES): Cc1nc2nc(-c3cccnc3)nn2c(C)c1CC(=O)Nc1cccc(C(F)(F)F)c1
InChIKey: MTJCWZPTCSKXKK-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of human TRKA at active state assessed as inhibition of substrate phosphorylation using fluorescently-labelled peptide as substrate by caliper assay
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 426.4, ALogP 4, HBA 6, HBD 1, PSA 85.07, QED 0.53
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCC4)c(Cl)cn2)C1
InChIKey: YFAKZUMJVBULBO-UONOGXRCSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 401.9, ALogP 3.18, HBA 5, HBD 2, PSA 88.91, QED 0.82
Compound (SMILES): CN1CC=C(c2c(O)cc(O)c3c(=O)cc(-c4ccc(Sc5nc6ccccc6n5C)cc4Cl)oc23)CC1
InChIKey: BTDCUFCJAWQJCI-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of human GSK3alpha by ADP-Glo assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 546.05, ALogP 6.28, HBA 8, HBD 2, PSA 91.73, QED 0.27
Compound (SMILES): N#Cc1ccc(Nc2nccc([C@@H](O)c3ccc(-c4ccc(C#N)cc4)cc3C(F)(F)F)n2)cc1
InChIKey: YGDJSUJAJDJUHW-DEOSSOPVSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 471.44, ALogP 5.73, HBA 6, HBD 2, PSA 105.62, QED 0.39
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1CSSC[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-AKSMUQGVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 1117.33
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3c(F)cccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: UHXVSCQTWQLUSR-GLEMDPEOSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 0.3311 nM (pChEMBL 9.479999542236328)
Descriptors: MW 1092.25
Compound (SMILES): Cc1cc(-c2ccc3c(c2)-c2nnc(Nc4cccc(C(F)(F)F)c4)n2CCO3)ccn1
InChIKey: PNOVIOUSABCJCS-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 437.43, ALogP 5.47, HBA 6, HBD 1, PSA 64.86, QED 0.46
Compound (SMILES): C/C(=N\Nc1nc(-c2ccc(Cl)cc2)cs1)c1nnn(-c2ccc(Cl)cc2)c1C
InChIKey: QZKHIYMJTANUNW-WYMPLXKRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 443.36, ALogP 5.84, HBA 7, HBD 1, PSA 67.99, QED 0.31
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(C)c3ccc(C(F)(F)F)cc34)cc2)cc1
InChIKey: KOQJZRRRDHXPJJ-MHZLTWQESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 0.59 nM (pChEMBL 9.229999542236328)
Descriptors: MW 576.66, ALogP 6.85, HBA 4, HBD 1, PSA 53.01, QED 0.3
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)N/N=C/c2cccc(O)c2)cc1
InChIKey: LUSNWRGCSGDUFN-CCVNUDIWSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 514.57, ALogP 3.77, HBA 9, HBD 4, PSA 151.55, QED 0.23
Compound (SMILES): Cc1ccc(CNC(=O)C(CC(C)O)N(C)CCC=C(c2sccc2C)c2sccc2C)cc1
InChIKey: DDPFFCOBMMTWNP-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 12302.69 nM (pChEMBL 4.909999847412109)
Descriptors: MW 496.74, ALogP 5.94, HBA 5, HBD 2, PSA 52.57, QED 0.35
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2ccc3c(N4CCOCC4)c(C(C)=O)c(=O)oc3c2)ncc1F
InChIKey: RDOKVGWGKMHBMG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/Cyclin E (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay
Measurement: IC50 = 1009 nM (pChEMBL 6)
Descriptors: MW 508.48, ALogP 4.32, HBA 9, HBD 1, PSA 106.79, QED 0.3
Compound (SMILES): C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BQMSKLCEWBSPPY-IKVTXIKFSA-N
Target: G-protein coupled receptor 183 (SINGLE PROTEIN), Mus musculus
UniProt: Q3U6B2
Assay: Agonist activity at Go2-q-coupled mouse EBI2 expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis
Measurement: EC50 = 0.702 nM (pChEMBL 9.149999618530273)
Descriptors: MW 418.66, ALogP 5.47, HBA 3, HBD 3, PSA 60.69, QED 0.52
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: YJQSLXCSWOBYML-MCRGWJRVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 49.3 nM (pChEMBL 7.309999942779541)
Descriptors: MW 1097.29
Compound (SMILES): CN1C(=O)c2ccccc2N(C)c2cc(N[C@H]3CC[C@H](O)CC3)ncc21
InChIKey: XDCQYSVFUPULSL-HDJSIYSDSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 in human PBMC assessed as reduction in LPS-induced TNFalpha secretion preincubated for 1 hr followed by LPS-stimulation and measured after 20 hrs by magnetic beads technique based assay
Measurement: EC50 = 2110 nM (pChEMBL 5.679999828338623)
Descriptors: MW 352.44, ALogP 3.15, HBA 5, HBD 2, PSA 68.7, QED 0.87
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(F)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: NHRLDLXSIQAXQX-AQPYCOETSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding affinity to human adenosine A1 receptor assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 442.48, ALogP 0.5, HBA 9, HBD 4, PSA 125.19, QED 0.44
Compound (SMILES): CCN(c1ccc(C(=O)O)cn1)c1cc(OCC(C)C)c(C(C)C)cc1NC(=O)c1cc2cc3c4c(c2oc1=O)CCCN4CCC3
InChIKey: ULMIFUYGJNTQBU-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Binding affinity to human RXRalpha-LBD by fluorescence binding assay
Measurement: Kd = 257 nM (pChEMBL 6.590000152587891)
Descriptors: MW 638.76, ALogP 7.15, HBA 8, HBD 2, PSA 125.21, QED 0.17
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CO)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: IZZFNAUKHJUKPH-MTOWIIDVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 6.98 nM (pChEMBL 8.15999984741211)
Descriptors: MW 404.46, ALogP 0.23, HBA 7, HBD 4, PSA 111.49, QED 0.55
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3c(C)c(OC)cc(OC)c3C)c(=O)n(C)c2n1
InChIKey: XMTUBCFDOXDZIL-ZWKOTPCHSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) expressed in KATO -III cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 479.54, ALogP 2.11, HBA 9, HBD 2, PSA 116.6, QED 0.5
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: RHZYCASJFPXTCW-SRZZPIQSSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 423.46, ALogP 1.88, HBA 9, HBD 2, PSA 141.28, QED 0.29
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)cc2sc(N[C@@H]3CCCC[C@H]3O)nc12
InChIKey: QPANAVQRQRUDJJ-ZIAGYGMSSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 = 41000 nM (pChEMBL 4.389999866485596)
Descriptors: MW 401.49, ALogP 2.97, HBA 9, HBD 3, PSA 115.41, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): O=c1[nH]nc(-c2ccc(Cl)c(C(F)(F)F)c2)o1
InChIKey: SBBOPUCCCOEMDA-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 264.59, ALogP 2.7, HBA 3, HBD 1, PSA 58.89, QED 0.86
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)ccc2n1
InChIKey: AGMGRCAUAZCHPG-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 1267 nM (pChEMBL 5.900000095367432)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
Compound (SMILES): C[C@@H]1CN(c2ccc(S(C)(=O)=O)cc2)CCN1c1nccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: FEGJQPCXQMHGGC-JPAYEOGSSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in pooled human liver microsomes using dextromethorphan as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.68, ALogP 2.26, HBA 8, HBD 2, PSA 115.73, QED 0.61
Compound (SMILES): C[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-GUYCJALGSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human AMCase expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): Cc1nnc(-c2ccc3cnc(NC(=O)c4ccnc(N(C)C5CCN(C)CC5)c4)cc3c2)s1
InChIKey: ARQUTMKPMAEVSS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA 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 DYRKIA 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. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 473.61, ALogP 4.24, HBA 8, HBD 1, PSA 87.14, QED 0.46
Compound (SMILES): COC(=O)NS(=O)(=O)c1sc(CC(C)C)cc1-c1cccc(C(=O)Cn2ccnc2C(C)(C)C)c1
InChIKey: SPDXVIKELDWSMA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 3 mins followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 517.67, ALogP 5.04, HBA 8, HBD 1, PSA 107.36, QED 0.42
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(F)cc2)nc1C#N
InChIKey: KTUYYMOKNXBOLX-PKTZIBPZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 493.63, ALogP 4.91, HBA 5, HBD 2, PSA 101.88, QED 0.43
Compound (SMILES): Nc1nccc(COc2ccc3nc(NC4CCCCC4)sc3c2)c1Cl
InChIKey: ZXYVWKYLUPYZGL-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Binding affinity to human wild type PDGFRbeta (V582 to Y1009 residues) expressed in bacterial expression system by kinome scan assay
Measurement: Kd = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 388.92, ALogP 5.25, HBA 6, HBD 2, PSA 73.06, QED 0.62
Compound (SMILES): COc1ccc(-c2ccc3c(NC(=O)CCCCCCC(=O)NO)n[nH]c3c2)cc1
InChIKey: OQKZYTUPMGUCDP-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC2 (1 to end residues) expressed in sf9 insect cells using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 410.47, ALogP 4.02, HBA 5, HBD 4, PSA 116.34, QED 0.23
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnc4n3CCCC4)c(Cl)cn2)C1
InChIKey: XPZMRZUXNMEPOS-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 415.93, ALogP 3.57, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): CO[C@@]12CC[C@H](N[C@H](C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)O)C(C)C)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: QLMICPWFXLJOEI-AANUSGNESA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 1.16 nM (pChEMBL 8.9399995803833)
Descriptors: MW 579.69, ALogP 2.33, HBA 8, HBD 5, PSA 140.59, QED 0.3
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1ccccc1
InChIKey: OPDYSVLVMGRCCI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 537.03 nM (pChEMBL 6.269999980926514)
Descriptors: MW 280.37, ALogP 3.47, HBA 2, HBD 1, PSA 32.34, QED 0.93
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 493.4, ALogP 5.88, HBA 3, HBD 2, PSA 79.29, QED 0.48
Compound (SMILES): CC1(CN)CCN(c2cnc(Sc3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: HFZSVNQUAOVFHI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 PTP domain (237 to 535 residues) using DiFMUP as substrate preincubated for 30 mins and followed by substrate addition and measured by microplate reader method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 398.36, ALogP 4.08, HBA 6, HBD 2, PSA 81.06, QED 0.81
Compound (SMILES): CON(C)C(=O)Oc1ccc(-c2cc(=O)c3c(O)cc(OC(=O)N(C)OC)cc3o2)cc1
InChIKey: MAYVYUJUNJKXFY-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of rat cortex AChE using acetylthiocholine as substrate incubated for 15 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 444.4, ALogP 3.15, HBA 9, HBD 1, PSA 127.98, QED 0.59
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)CNCCNc3c4c(nc5ccccc35)CCCC4)c2)nc1OCC1CC1
InChIKey: MYLYCZDLVLCRLU-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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 585.73, ALogP 4.42, HBA 9, HBD 4, PSA 130.16, QED 0.18
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(C(=O)NCCNC(=O)CCc4cn(CCCCC5CCN(CC(=O)N6c7ccccc7NC(=O)c7ccccc76)CC5)cn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: OTWPYWJMLIDHOJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 275.42 nM (pChEMBL 6.559999942779541)
Descriptors: MW 984.17, ALogP 6.15, HBA 11, HBD 3, PSA 188.19, QED 0.05
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(NC(=O)CCCCCCCCC(=O)NO)cc3C2)c(O)cc1O
InChIKey: HBNSYDADLFRPNT-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using RHK-K(Ac)-AMC as substrate by fluorescence based assay
Measurement: IC50 = 3720 nM (pChEMBL 5.429999828338623)
Descriptors: MW 511.62, ALogP 4.94, HBA 6, HBD 5, PSA 139.2, QED 0.16
Compound (SMILES): Nc1ccc(Nc2ncc(C(F)(F)F)c(NC3CC3)n2)cc1
InChIKey: XWPNWIGEIJKOEC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: ULK1 inhibition assay: Gamma-32P assays to measure ULK1 kinase activity were performed as previously described. Briefly, Flag ULK1 was transfected into HEK293T cells and 20 hours later treated as indicated. The immmunoprecipitate was washed in IP buffer 3 times, and washed in kinase buffer (25 mM MOPS, pH 7.5, 1 mM EGTA, 0.1 mM Na3VO4, 15 mM MgCl2,). Hot and cold ATP were added at a 100 μM final concentration. As substrates, GST or the recombinant protein GST-Atg101 purified from E. coli were used at 1 μg for each reaction. Reactions were boiled, run out on SDS page gel. The gel was dried, and imaged using PhosphoImager software. For cold assays to asses ULK1, Flag ULK1 which was transiently overexpressed and immunoprecipited from HEK293T cells. Reactions were then run out on SDS page gel, transferred to PVDF membrane and blotted for total levelsFluorescence MicroscopyVps34flox/flox MEFs were reconstituted with Flag-VPS34 and either p40FX or GFP-DFCP1. 48 hours post infection with adenovirus expressing Cre recombinase (MOI of 100), cells were plated on glass coverslips at a density of 3×105 cells per well in 6-well tissue culture plates. 18 h later, cells were fixed in 4% PFA in PBS for 10 minutes and permeabilized in 0.2% Triton in PBS for 10 minutes. The following primary antibodies were used: mouse anti-Myc epitope and LC3B XP antibody (2276 and 3868 respectively, Cell Signaling Technologies). Secondary antibodies were anti-rabbit Alexa488 and anti-mouse Alexa594 (Molecular Probes, 1:1000. Cells were then fixed and counter stained with DAPI. Coverslips were mounted in FluoromountG (SouthernBiothech). Images were acquired on a Zeiss Axioplan2 epifluorescence microscope coupled to the Openlab software. Confocal images of mitotracker were taken on Zeiss LSM 710 laser scanning confocal microscope. 10 random fields per condition were acquired using the 100× objective and representative images shown. Glass coverslips were mounted directly on plate with FluoromountG and images taken on Zeiss Axioplan2 epifluorescence microscope.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 309.3, ALogP 3.4, HBA 5, HBD 3, PSA 75.86, QED 0.75
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ncc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)F
InChIKey: HHXTYKXNOKWJQP-FATZIPQQSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Binding Assay: hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials [Sanguinetti et al., Nature, 2006, 440, 463-469.] and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 494.51, ALogP 4.45, HBA 5, HBD 2, PSA 60.08, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: ZSYKTLDQSMAEFY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 488.42, ALogP 1.59, HBA 5, HBD 4, PSA 147.46, QED 0.27
Compound (SMILES): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3ccc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)cc3C2)cc1
InChIKey: WQBKMBBBWFAMFH-VAWYXSNFSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): N#Cc1ccc(Nc2nccc([C@H](O)c3ccc(-c4ccc(C#N)cc4)cc3C(F)(F)F)n2)cc1
InChIKey: YGDJSUJAJDJUHW-XMMPIXPASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 933.3 nM (pChEMBL 6.03000020980835)
Descriptors: MW 471.44, ALogP 5.73, HBA 6, HBD 2, PSA 105.62, QED 0.39