lovingscience/chembl-v37-raw-activities huggingface dataset:
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: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (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 = 54.4 nM (pChEMBL 7.260000228881836)
Descriptors: MW 1097.29
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: Binding affinity to human wild type PDGFRbeta (V582 to Y1009 residues) expressed in bacterial expression system by kinome scan assay
Measurement: Kd = 4900 nM (pChEMBL 5.309999942779541)
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: 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 = 550 nM (pChEMBL 6.260000228881836)
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (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: Bone morphogenetic protein receptor type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13873
Assay: Inhibition of human BMPR2 using MBP as substrate by [gamma-33P]-ATP assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
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), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse AMCase expressed in 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 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): Nc1nccc(COc2ccc3nc(NC4CCCCC4)sc3c2)c1Cl
InChIKey: ZXYVWKYLUPYZGL-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Inhibition of CSF1R in mouse NFS-60 cells assessed as reduction in CSF-induced cell proliferation after 72 hrs by CellTiter-Glo assay
Measurement: IC50 = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 388.92, ALogP 5.25, HBA 6, HBD 2, PSA 73.06, QED 0.62
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity : For the characterization of test substances in respect of FP antagonism, PGF2α-induced calcium flux in FP-expressing CHEM1 cells (Millipore, HTS093C) was used.3000 cells in 25 μl of full medium [DMEM F12, 10% FCS, 1.35 mM sodium pyruvate, 20 mM HEPES, 4 mM GlutaMAX, 2% sodium bicarbonate, 1% Pen/Strep, 1% 100× non-essential amino acids] are sown per well of a 384 multititer plate (from Greiner, TC plate, black with clear base) and incubated at 37° C./5% CO2 for 24 hours. Prior to the measurement, the medium is replaced by 30 μl of Fluo-8 AM loading buffer [calcium-free Tyrode (130 mM NaCl, 5 mM KCl, 20 mM HEPES, 1 mM MgCl2, 4.8 mM NaHCO3, pH 7.4), 2 mM CaCl2, 1× SmartBlock (from CANDOR Bioscience GmbH), 4.5 mM Probenecid, 5 μM Fluo-8 AM, 0.016% Pluronic, 0.04% Brilliant black] and incubated at 37° C./5% CO2 for 30 minutes. The test substance is prepared in DMSO in various concentrations as a dose-response curve (starting concentration 10 mM, dilution factor 3.16) and prediluted 1:50 with calcium-free Tyrode/2 mM CaCl2. 10 μl of the prediluted substance solution are added to the Fluo-8-laden cells and incubated at 37° C./5% CO2 for 10 minutes. The FP receptor is activated by adding 20 μl of 3 nM (final concentration) PGF2α in calcium-free Tyrode/2 mM CaCl2/0.04% Brilliant black, and the calcium flux is determined by measuring the fluorescence at ex. 470 nm/em. 525 nm in a fluorescence measuring instrument (FLIPR Tetra, Molecular Devices) for 120 seconds.
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
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 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of wild-type SHP1 (2 to 595 residues) (unknown origin) using DiFMUP as substrate and measured by biochemical assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 398.36, ALogP 4.08, HBA 6, HBD 2, PSA 81.06, QED 0.81
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 M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Binding affinity to human muscarinic M2 receptor expressed in CHO-K9 cells assessed as unspecific binding at Kd incubated in dark at 22 degree C for 2 hrs in presence of atropine by FACSCantoII flow cytometric saturation binding study relative to control
Measurement: Kd = 4.365 nM (pChEMBL 8.359999656677246)
Descriptors: MW 984.17, ALogP 6.15, HBA 11, HBD 3, PSA 188.19, QED 0.05
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: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
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): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3ccc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)cc3C2)cc1
InChIKey: WQBKMBBBWFAMFH-VAWYXSNFSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 (875 to end residues) using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of human full length recombinant DYRK2 using casein substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Nc1n[nH]c(N2CCC(N3C[C@H](CO)OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: NFCCGJZRWCEETB-DLBZAZTESA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC:276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm. Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Tecan Spark multimode plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 406.92, ALogP 1.31, HBA 7, HBD 3, PSA 103.53, QED 0.69
Compound (SMILES): CCOC(=O)CNc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: ZMVUYNQVYVTCAD-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 404.43, ALogP 2.1, HBA 9, HBD 2, PSA 116.54, QED 0.47
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor by liquid scintillation counting
Measurement: Ki = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
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: Receptor Binding Assay: 5-HT1A: Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human 5-HT1A receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-8-OH-DPAT (final concentration 1 nM, Kd 0.8 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 0.1 mM EDTA, 0.1% ascorbic acid) were transferred to polypropylene 96-well microplate using 96-wells pipetting station Rainin Liquidator (MettlerToledo). Serotonin (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 27° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 407.89, ALogP 4.13, HBA 3, HBD 2, PSA 44.37, QED 0.68
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
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: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in human U2OS cells assessed as increase in beta arrestin2 recruitment incubated for 90 mins by pathhunter beta-arrestin assay
Measurement: EC50 = 1329 nM (pChEMBL 5.880000114440918)
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: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Selectivity interaction (Methyltransferase panel) EUB0000196bCl EHMT1
Measurement: EC50 > 10000 nM (pChEMBL 5)
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](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
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): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccccc4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: JDOWDLRLLSFBOY-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28647
Assay: Displacement of [3H]NECA from rat adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki = 806 nM (pChEMBL 6.090000152587891)
Descriptors: MW 514.61, ALogP 6.74, HBA 6, HBD 1, PSA 76.88, QED 0.28
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: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2ccc3c(c2)C(=O)N(C)CC3)CC1
InChIKey: SLPNWORIUMAUFP-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31390
Assay: Receptor Binding Assay: Histamine H1: (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 (potassium dihydrogen phosphate 1.36 g, 0.1 mol/L sodium hydroxide 79 ml, metered to 200 ml with double-distilled water) was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 uL of membrane preparation was added into each reaction tube. (3) 100 uL of buffer was added into the total binding tube (TB), 100 uL of promethazine (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 uL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 uL of radioactive ligand 3H-pyrilamine 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 of the reaction tubes was incubated at 30° C. for 60 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and the ice-chilled assay buffer was used for adequate washing. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation solution was added and blended. 2* Isotope ligand [3H]-5-CT (85.4 Ci/mmol) was purchased from PerkinElmer Company; (+-)-pindolol was purchased from RBI Company; GF/C glass fiber filter paper was purchased from Whatman Company; Tris was imported and divided into aliquots; PPO and POPOP were purchased from Shanghai No. 1 Reagent Factory; liposoluble scintillation cocktail was purchased from Shanghai Reagent Factory. Beckman LS-6500 Multi-function Liquid Scintillation Counter was used.
Measurement: Ki > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 409.53, ALogP 2.91, HBA 5, HBD 0, PSA 45.25, QED 0.66
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: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (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 = 354.81 nM (pChEMBL 6.449999809265137)
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 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC4R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 0.021 nM (pChEMBL 10.680000305175781)
Descriptors: MW 1092.25
Compound (SMILES): Cc1ccc(CNC(=O)C(CC(C)O)N(C)CCC=C(c2sccc2C)c2sccc2C)cc1
InChIKey: DDPFFCOBMMTWNP-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 7079.46 nM (pChEMBL 5.150000095367432)
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 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of CDK5/p25 (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 = 1261 nM (pChEMBL 5.900000095367432)
Descriptors: MW 508.48, ALogP 4.32, HBA 9, HBD 1, PSA 106.79, QED 0.3
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: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (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 = 53.7 nM (pChEMBL 7.269999980926514)
Descriptors: MW 1097.29
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 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Binding affinity to human wild type PDGFRalpha (V575 to D1002 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd = 4100 nM (pChEMBL 5.389999866485596)
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: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
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: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Biochemical Notum Enzymatic Activity Assay: An Echo liquid handler was used to acoustically dispense 500 nL of compounds into dry Greiner 384-well plates (catalog #781076), followed by 25 μL of 2 μM trisodium 8-octanoyloxypyrene-1,3,6-trisulfonate (OPTS, Sigma #74875) solution in 50 mM Tris, 5 mM CaCl2), 0.5 mM MgCl2, pH 7.4 assay buffer, and 25 μL of 2.38 nM notum carboxyesterase enzyme solution in the same buffer to every well in the assay plate. After 1 hour incubation at room temperature, fluorescence was measured on a PheraSTAR FSX microplate reader with an excitation wavelength of 485 nm and emission wavelength of 520 nm.
Measurement: IC50 = 20.1 nM (pChEMBL 7.699999809265137)
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-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37173
Assay: Inhibition of human TGFBR2 using MBP as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 587.2 nM (pChEMBL 6.230000019073486)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
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), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse AMCase expressed in 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: Ki = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): CC1(CN)CCN(c2cnc(Sc3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: HFZSVNQUAOVFHI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of wild-type PTP1B (2 to 435 residues) (unknown origin) using DiFMUP as substrate and measured by biochemical assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 398.36, ALogP 4.08, HBA 6, HBD 2, PSA 81.06, QED 0.81
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: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant human FLT3 D835Y mutant (564 to end residues) using EAIYAAPFAKKK as substrate at 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86Z02
Assay: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 921 nM (pChEMBL 6.039999961853027)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Nc1n[nH]c(N2CCC(N3C[C@H](CO)OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: NFCCGJZRWCEETB-DLBZAZTESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: ERG Channel Binding Assay: Fluorescence polarization assay based on the principle of fluorescence polarization where a red-shifted fluorescent tracer is displaced from the hERG channel by compounds that bind to the channel was used to establish the binding of the compounds to hERG channel. Briefly, the compounds in serial dilutions were incubated with a membrane fraction containing hERG channel protein and a high-affinity red fluorescent hERG channel ligand in black 384-well plate. The reaction was incubated for 4 h at room temperature followed by the measurement of the fluorescence polarization using Tecan Spark multimode plate reader at excitation wavelength of 535 nm and emission wavelength 590 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 62500 nM (pChEMBL 4.199999809265137)
Descriptors: MW 406.92, ALogP 1.31, HBA 7, HBD 3, PSA 103.53, QED 0.69
Compound (SMILES): CCOC(=O)CNc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: ZMVUYNQVYVTCAD-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 404.43, ALogP 2.1, HBA 9, HBD 2, PSA 116.54, QED 0.47
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor by liquid scintillation counting
Measurement: Ki = 77.62 nM (pChEMBL 7.110000133514404)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCNc2ccccc2)CC1
InChIKey: BZPOPHHMWUCUHD-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 407.89, ALogP 4.13, HBA 3, HBD 2, PSA 44.37, QED 0.68
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
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: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR stably expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 1 hr by liquid scintillation counting assay
Measurement: EC50 = 301 nM (pChEMBL 6.519999980926514)
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: Histone-lysine N-methyltransferase EZH1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92800
Assay: Selectivity interaction (Methyltransferase panel) EUB0000196bCl EZH1
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.53, ALogP 3, HBA 4, HBD 2, PSA 78.51, QED 0.6
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: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (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 = 168 nM (pChEMBL 6.78000020980835)
Descriptors: MW 1117.33
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2ccc3c(N4CCOCC4)c(C(C)=O)c(=O)oc3c2)ncc1F
InChIKey: RDOKVGWGKMHBMG-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin D3 (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 = 336 nM (pChEMBL 6.46999979019165)
Descriptors: MW 508.48, ALogP 4.32, HBA 9, HBD 1, PSA 106.79, QED 0.3
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: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (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 = 258.7 nM (pChEMBL 6.590000152587891)
Descriptors: MW 1097.29
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)cc2sc(N[C@@H]3CCCC[C@H]3O)nc12
InChIKey: QPANAVQRQRUDJJ-ZIAGYGMSSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Inhibition of CSF1R in mouse NFS-60 cells assessed as reduction in CSF-induced cell proliferation after 72 hrs by CellTiter-Glo assay
Measurement: IC50 = 504 nM (pChEMBL 6.300000190734863)
Descriptors: MW 401.49, ALogP 2.97, HBA 9, HBD 3, PSA 115.41, QED 0.58
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)ccc2n1
InChIKey: AGMGRCAUAZCHPG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human KDR using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 13410 nM (pChEMBL 4.869999885559082)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
Compound (SMILES): C[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-GUYCJALGSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of tracer red binding to human ERG expressed in HEK293 cell membranes measured after 2 to 6 hrs by fluorescence polarization assay
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity : For the characterization of test substances in respect of FP antagonism, PGF2α-induced calcium flux in FP-expressing CHEM1 cells (Millipore, HTS093C) was used.3000 cells in 25 μl of full medium [DMEM F12, 10% FCS, 1.35 mM sodium pyruvate, 20 mM HEPES, 4 mM GlutaMAX, 2% sodium bicarbonate, 1% Pen/Strep, 1% 100× non-essential amino acids] are sown per well of a 384 multititer plate (from Greiner, TC plate, black with clear base) and incubated at 37° C./5% CO2 for 24 hours. Prior to the measurement, the medium is replaced by 30 μl of Fluo-8 AM loading buffer [calcium-free Tyrode (130 mM NaCl, 5 mM KCl, 20 mM HEPES, 1 mM MgCl2, 4.8 mM NaHCO3, pH 7.4), 2 mM CaCl2, 1× SmartBlock (from CANDOR Bioscience GmbH), 4.5 mM Probenecid, 5 μM Fluo-8 AM, 0.016% Pluronic, 0.04% Brilliant black] and incubated at 37° C./5% CO2 for 30 minutes. The test substance is prepared in DMSO in various concentrations as a dose-response curve (starting concentration 10 mM, dilution factor 3.16) and prediluted 1:50 with calcium-free Tyrode/2 mM CaCl2. 10 μl of the prediluted substance solution are added to the Fluo-8-laden cells and incubated at 37° C./5% CO2 for 10 minutes. The FP receptor is activated by adding 20 μl of 3 nM (final concentration) PGF2α in calcium-free Tyrode/2 mM CaCl2/0.04% Brilliant black, and the calcium flux is determined by measuring the fluorescence at ex. 470 nm/em. 525 nm in a fluorescence measuring instrument (FLIPR Tetra, Molecular Devices) for 120 seconds.
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 493.4, ALogP 5.88, HBA 3, HBD 2, PSA 79.29, QED 0.48
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2X6
Assay: Inhibition of human recombinant HIPK2 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 484 nM (pChEMBL 6.320000171661377)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5HT2A receptor by liquid scintillation counting
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
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: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR stably expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 1 hr by liquid scintillation counting assay
Measurement: EC50 = 514 nM (pChEMBL 6.289999961853027)
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: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Selectivity interaction (Methyltransferase panel) EUB0000196bCl EZH2
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.53, ALogP 3, HBA 4, HBD 2, PSA 78.51, QED 0.6
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: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (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 = 169.82 nM (pChEMBL 6.769999980926514)
Descriptors: MW 1117.33
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2ccc3c(N4CCOCC4)c(C(C)=O)c(=O)oc3c2)ncc1F
InChIKey: RDOKVGWGKMHBMG-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P24863
Assay: Inhibition of CDK8/Cyclin C (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 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 508.48, ALogP 4.32, HBA 9, HBD 1, PSA 106.79, QED 0.3
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: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (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 = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 1097.29
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)ccc2n1
InChIKey: AGMGRCAUAZCHPG-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 7450 nM (pChEMBL 5.130000114440918)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
Compound (SMILES): C[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-GUYCJALGSA-N
Target: Chitinase-3-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36222
Assay: Binding affinity to human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells assessed as dissociation constant incubated for 10 mins by NT647 fluorescent dye based microscale thermophoresis assay
Measurement: Kd > 100000 nM (pChEMBL 4)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity : For the characterization of test substances in respect of FP antagonism, PGF2α-induced calcium flux in FP-expressing CHEM1 cells (Millipore, HTS093C) was used.3000 cells in 25 μl of full medium [DMEM F12, 10% FCS, 1.35 mM sodium pyruvate, 20 mM HEPES, 4 mM GlutaMAX, 2% sodium bicarbonate, 1% Pen/Strep, 1% 100× non-essential amino acids] are sown per well of a 384 multititer plate (from Greiner, TC plate, black with clear base) and incubated at 37° C./5% CO2 for 24 hours. Prior to the measurement, the medium is replaced by 30 μl of Fluo-8 AM loading buffer [calcium-free Tyrode (130 mM NaCl, 5 mM KCl, 20 mM HEPES, 1 mM MgCl2, 4.8 mM NaHCO3, pH 7.4), 2 mM CaCl2, 1× SmartBlock (from CANDOR Bioscience GmbH), 4.5 mM Probenecid, 5 μM Fluo-8 AM, 0.016% Pluronic, 0.04% Brilliant black] and incubated at 37° C./5% CO2 for 30 minutes. The test substance is prepared in DMSO in various concentrations as a dose-response curve (starting concentration 10 mM, dilution factor 3.16) and prediluted 1:50 with calcium-free Tyrode/2 mM CaCl2. 10 μl of the prediluted substance solution are added to the Fluo-8-laden cells and incubated at 37° C./5% CO2 for 10 minutes. The FP receptor is activated by adding 20 μl of 3 nM (final concentration) PGF2α in calcium-free Tyrode/2 mM CaCl2/0.04% Brilliant black, and the calcium flux is determined by measuring the fluorescence at ex. 470 nm/em. 525 nm in a fluorescence measuring instrument (FLIPR Tetra, Molecular Devices) for 120 seconds.
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 493.4, ALogP 5.88, HBA 3, HBD 2, PSA 79.29, QED 0.48
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H422
Assay: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5HT2A receptor by liquid scintillation counting
Measurement: Ki = 51.29 nM (pChEMBL 7.289999961853027)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
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: Agonist activity at human NTS1 expressed in HEK293 cells co-expressing Galphaq/RlucII/GFP10-Ggamma1/Gbeta1 assessed as increase in Galphaq activation incubated for 10 mins in presence of coelenterazine 400A by BRET assay
Measurement: EC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 1394.69