lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): FCCCN1CC(Nc2ccc([C@@H]3c4ccc5[nH]ncc5c4C[C@@H](C(F)F)N3CC(F)F)nc2)C1
InChIKey: FWWHNGKEZAFESY-GMAHTHKFSA-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 = 0.68 nM (pChEMBL 9.170000076293945)
Descriptors: MW 494.51, ALogP 4.26, HBA 5, HBD 2, PSA 60.08, QED 0.44
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: AYKSFHQCPBPUPW-QFIPXVFZSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 472.55, ALogP 1.14, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): O=c1cc(CN2CCN(Cc3ccccc3)CC2)c2ccc(OCc3cc(F)ccc3F)cc2o1
InChIKey: IXUKWFNCIDORAD-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 476.52, ALogP 4.97, HBA 5, HBD 0, PSA 45.92, QED 0.35
Compound (SMILES): O=c1ccoc2ccc(OCCCCN3CCCC3)cc12
InChIKey: SJZOAVOKRIVTGW-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B
Measurement: IC50 = 19600 nM (pChEMBL 4.710000038146973)
Descriptors: MW 287.36, ALogP 3.05, HBA 4, HBD 0, PSA 42.68, QED 0.77
Compound (SMILES): CC(=O)N1CCC2(CC1)c1cc(C(=O)NCc3ccccc3Cl)ccc1N(S(=O)(=O)c1ccc(F)cc1)C2C
InChIKey: MOEVGYNBSQJEFD-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of buserelin-induced response preincubated for 20 mins followed by buserelin addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 570.09, ALogP 4.89, HBA 4, HBD 1, PSA 86.79, QED 0.47
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2ccc(C(F)(F)F)cc2)cc1
InChIKey: NCIKNHSGMWWKJR-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 324.26, ALogP 3.08, HBA 3, HBD 3, PSA 78.43, QED 0.6
Compound (SMILES): C#CCN1CCCC(CO)C1
InChIKey: SEGPGNSXCVPIKQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 153.22, ALogP 0.32, HBA 2, HBD 1, PSA 23.47, QED 0.58
Compound (SMILES): Cc1nc(OCc2ccc(F)cc2)c(C(=O)NC2CCCCCC2)cc1Br
InChIKey: LEHIEWISZPIBHW-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL in human U937 cells using [glycerol-1,2,3-3H]2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.34, ALogP 5.32, HBA 3, HBD 1, PSA 51.22, QED 0.65
Compound (SMILES): Nc1nn2c(-c3ccc(Br)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: VPJWECUQRFSGFO-WCWDXBQESA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 54.3 nM (pChEMBL 7.260000228881836)
Descriptors: MW 472.33, ALogP 3.8, HBA 8, HBD 2, PSA 141.09, QED 0.43
Compound (SMILES): O=C1c2nc3ccccc3n2CCN1CCCCOc1ccc(OC(F)(F)F)cc1
InChIKey: QRCUMXUPIXTGPF-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.4, ALogP 4.25, HBA 5, HBD 0, PSA 56.59, QED 0.54
Compound (SMILES): Cn1c(C(N)=O)cc2c1-c1ccncc1OC21CCC1
InChIKey: YHBCYQIXVZFFIV-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 = 27.6 nM (pChEMBL 7.559999942779541)
Descriptors: MW 269.3, ALogP 1.96, HBA 4, HBD 1, PSA 70.14, QED 0.86
Compound (SMILES): CC1(C)OC(=O)c2ccc(Nc3ncc(-c4nc(C56CCN(CC5)CC6)no4)c(N[C@H](CO)c4ccccc4)n3)cc21
InChIKey: RVFYCRCCTDEQQD-XMMPIXPASA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in anti-CD3/anti-CD28-stimulated human T-cells assessed as inhibition of SLP76 phosphorylation preincubated for 1 hr followed by anti-CD3/CD28 stimulation for 30 mins by AlphaLISA assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 567.65, ALogP 4.56, HBA 11, HBD 3, PSA 138.53, QED 0.26
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4cnc5ccccc5c4)cc3c2)cn1
InChIKey: GUGOTVDQIVQZBF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa 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 ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is 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 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is 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 = 4464 nM (pChEMBL 5.349999904632568)
Descriptors: MW 379.42, ALogP 4.44, HBA 5, HBD 1, PSA 72.7, QED 0.5
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1ccc(F)cc1
InChIKey: HJFHBVCVDRZKOR-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant full length N-terminal polyHis-tagged PI3Kgamma (114 to 1102 residues) (unknown origin) expressed in baculovirus infected Hi-5 cells using PIP2 as substrate in presence of ATP incubated for 20 mins by Alphascreen assay
Measurement: IC50 = 191 nM (pChEMBL 6.71999979019165)
Descriptors: MW 391.39, ALogP 3.72, HBA 7, HBD 2, PSA 105.44, QED 0.55
Compound (SMILES): CCC1(Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)CCCNC1
InChIKey: ICAYWDBIWWQYCA-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 355.87, ALogP 4.22, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): C#CCN1CCCC(OC(=O)Nc2ccccc2)C1
InChIKey: ZMAXJNFYRWSNFA-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 258.32, ALogP 2.33, HBA 3, HBD 1, PSA 41.57, QED 0.85
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccncc4n3)C2)cc1
InChIKey: JVPPVCXAHQZJPI-QGZVFWFLSA-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 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-DOQBYECHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 15.4 nM (pChEMBL 7.809999942779541)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4)ccn2)C1
InChIKey: ASEPZBUAEOJUCM-DLBZAZTESA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MCF7 cells assessed as reduction in RNA Polymerase 2 CTD phosphorylation at Ser2 residues measured after 6 hrs by immunofluorescence assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 381.48, ALogP 2.91, HBA 5, HBD 2, PSA 88.91, QED 0.85
Compound (SMILES): CC(=O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: VBXUAFKZCVKOQN-ZDUSSCGKSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 335.41, ALogP 2.99, HBA 5, HBD 3, PSA 82.7, QED 0.64
Compound (SMILES): CCS(=O)(=O)c1ccc(CNC(=O)Nc2cc(Cl)c(-c3ccccc3OC(F)(F)F)c(Cl)c2)cc1
InChIKey: JSCWNFIGCHHELZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inhibitory Activity Assay: 1. Preparation of RORgamma Buffer Solution10 mL of DTT and 100 mL buffer solution were gently mixed together and ready to use.2. Preparation of Compound SolutionThe concentration of compound solution started from 7.5 mM to 0.25 mM, which was diluted by every 3 folds from 7.5 nM with 10 concentrations totally.3. Preparation of Protein Mixturea. 40 nM B-RORgamma LBD solution and 20 nM SA-APC solution were gently mixed together. The reaction mixture was incubated for 15 minutes at room temperature. Then 400 nM Biotin was added to the described above mixture. After gently mixed together, the resulting mixture was incubated for 10 minutes at room temperature.b. 40 nM Bioin-SRC1 solution and 10 nM SA-eu solution were gently mixed together, and the reaction mixture was incubated for 15 minutes at room temperature. Then 200 nM Biotin was added to the described above mixture. After gently mixed together, the resulting mixture was incubated for 10 minutes at room temperature.c. The described above two pre-mixes were gently mixed together with a ratio of 1:1, and the resulting mixture was incubated for 5 minutes at room temperature.
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 547.38, ALogP 6.67, HBA 4, HBD 2, PSA 84.5, QED 0.35
Compound (SMILES): C=CC(=O)Nc1ccc(-c2ccnc(Nc3cnn(CCOC)c3)n2)cc1
InChIKey: CKHJIDHRSXTJER-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 cytoplasmic domain (809 to 1153+9 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 1079 nM (pChEMBL 5.96999979019165)
Descriptors: MW 364.41, ALogP 2.85, HBA 7, HBD 2, PSA 93.96, QED 0.6
Compound (SMILES): CC[C@H](N[C@@H]1CC[C@@]2(OC)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3C)[C@H]1O5)C(=O)O
InChIKey: FGPMICJYDSZBIT-AXENNSGJSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 5.47 nM (pChEMBL 8.260000228881836)
Descriptors: MW 402.49, ALogP 1.65, HBA 6, HBD 3, PSA 91.26, QED 0.69
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1C
InChIKey: KXKAWIWAQIOGGO-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 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 419.46, ALogP 3.53, HBA 5, HBD 2, PSA 87.22, QED 0.62
Compound (SMILES): COc1ccc(NC(=O)CSc2nc3ccc(I)cc3c(=O)n2-c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: SGPPLUZVQGSQDM-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 142.4 nM (pChEMBL 6.849999904632568)
Descriptors: MW 622.47, ALogP 3.38, HBA 8, HBD 2, PSA 133.38, QED 0.18
Compound (SMILES): CC(C)(CO)NC(=O)c1cc(C(C)(C)C)n(-c2ccc(C(F)(F)F)cn2)n1
InChIKey: IIANDZHTDXIIKC-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in HEK293 cells after 24 hrs by luciferase reporter gene assay based Tango beta-arrestin recruitment method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.4, ALogP 3.08, HBA 5, HBD 2, PSA 80.04, QED 0.85
Compound (SMILES): Fc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: IVVMEAPLRJRWHE-JTQLQIEISA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 345.81, ALogP 3.58, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): Nc1nc(-c2ccccc2O)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: HMTBCEGHBBCZMF-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 319.32, ALogP 1.83, HBA 7, HBD 2, PSA 98.44, QED 0.59
Compound (SMILES): O=C(Nc1ccccc1)OCC1CCN(Cc2ccccc2)CC1
InChIKey: IKTRKOHDYGDICC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 324.42, ALogP 4.15, HBA 3, HBD 1, PSA 41.57, QED 0.9
Compound (SMILES): Fc1ccc(-c2ccc(OCCCN3CCN(c4ccncc4)CC3)cc2)cc1
InChIKey: FRXKBKSVWAOOCI-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]histamine from Gialpha2/Gbeta1gamma2-coupled human H4R expressed in Sf9 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 391.49, ALogP 4.48, HBA 4, HBD 0, PSA 28.6, QED 0.56
Compound (SMILES): CC(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: RPWBQONKJLUMGK-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 369.86, ALogP 3.64, HBA 5, HBD 3, PSA 82.7, QED 0.61
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2nc(-c3ncccc3F)ccc2N)C[C@@H](O)[C@]1(C)O
InChIKey: QVCLVTVRXGXXOR-FTMGGNRSSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin)
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 451.5, ALogP 3.14, HBA 7, HBD 4, PSA 134.25, QED 0.48
Compound (SMILES): C=CCOc1ccc2oc(CC)cc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: UXEFZEYHZIIDPC-YLAFAASESA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 433 nM (pChEMBL 6.360000133514404)
Descriptors: MW 271.36, ALogP 3.62, HBA 3, HBD 1, PSA 48.39, QED 0.82
Compound (SMILES): COc1ccc(N2CCN(Cc3cc(=O)oc4cc(OCc5ccccc5)ccc34)CC2)cc1
InChIKey: UAEWHFJNUIAMSI-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 456.54, ALogP 4.7, HBA 6, HBD 0, PSA 55.15, QED 0.38
Compound (SMILES): CCc1cnc(N[C@@H]2CCCNC2)nc1-c1n[nH]c2ncccc12
InChIKey: RMQZFHNZKHTFFQ-GFCCVEGCSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 323.4, ALogP 2.14, HBA 6, HBD 3, PSA 91.41, QED 0.68
Compound (SMILES): COc1cc(OC)c2c(N3CCN(C)CC3)nc(-c3cc(C)c(OCCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: NTUCJWZWDDQYER-UHFFFAOYSA-N
Target: Histone deacetylase 3/NCoR1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O75376
Assay: Inhibition of recombinant human GST-fused HDAC3/NCOR1 (397 to 503 residues) expressed in baculovirus infected insect cells using Ac-Leu-Gly-Lys(Ac)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 = 79.17 nM (pChEMBL 7.099999904632568)
Descriptors: MW 537.66, ALogP 4.13, HBA 9, HBD 2, PSA 109.28, QED 0.21
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1[nH]c(-c2ccc(F)cc2)nc1C(N)=O
InChIKey: QXMVYSCRIRLZNR-IBGZPJMESA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 457.55, ALogP 2.96, HBA 5, HBD 3, PSA 121.18, QED 0.42
Compound (SMILES): Ic1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BRLYHLKTEZGXJD-NSHDSACASA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 419.27, ALogP 3.39, HBA 4, HBD 3, PSA 65.63, QED 0.57
Compound (SMILES): Fc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)n[nH]c12
InChIKey: LOVXTLJVBKIDNT-VIFPVBQESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 346.8, ALogP 2.98, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): COCCN1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: WNTWPMDPWXFJJJ-AWEZNQCLSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 385.9, ALogP 3.8, HBA 5, HBD 2, PSA 66.07, QED 0.68
Compound (SMILES): Cc1ccn2c(-c3ccc(O)cc3)c(N)nc2c1
InChIKey: MUCQSAHJCJDIRZ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: P54578
Assay: Inhibition of USP14 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 239.28, ALogP 2.6, HBA 4, HBD 2, PSA 63.55, QED 0.69
Compound (SMILES): Cn1cc(-c2cc(C(C)(C)O)ccc2OC2CC2)c2cc(C(=O)NCc3ccc(C(=O)NO)cc3)[nH]c2c1=O
InChIKey: UTSVADVXKCTABF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 530.58, ALogP 3.35, HBA 7, HBD 5, PSA 145.68, QED 0.17
Compound (SMILES): FC(F)(F)c1cnc(NC2C3CCC2NC3)nc1-c1c[nH]c2ccccc12
InChIKey: TXZFORDUGWJTSQ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 373.38, ALogP 3.81, HBA 4, HBD 3, PSA 65.63, QED 0.65
Compound (SMILES): CC(=O)NCCC(C(=O)NCc1ccccc1Cl)N(C)CCC=C(c1sccc1C)c1sccc1C
InChIKey: BYIMWNNOGMXRCA-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 = 6165.95 nM (pChEMBL 5.210000038146973)
Descriptors: MW 544.19, ALogP 6.04, HBA 5, HBD 2, PSA 61.44, QED 0.29
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(C(=O)O)cc1
InChIKey: GTVGUYLLAFHOLS-SRZZPIQSSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 239.2 nM (pChEMBL 6.619999885559082)
Descriptors: MW 388.39, ALogP 2.93, HBA 8, HBD 2, PSA 118.42, QED 0.31
Compound (SMILES): COc1cc2nccc(Oc3ccc(Nc4nccc5[nH]cc(-c6ccc(F)cc6)c(=O)c45)cc3F)c2cc1OC
InChIKey: SLRINRCTDNIRFQ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition Assay: A study on inhibition of protein kinases activity at in vitro biochemical levelMaterial and method: kinases such as c-Met, VEGFR-2, Axl and RET, obtained from Invitrogen; HTRF KinEASE; TK kit (Cisbio Company); 384-well plate (Greiner Company); ATP (Sigma Company), MgCl2 (Sigma Company); PHERAstar FS multifunctional plate reader (BMG Company); conventional centrifuge (StaiteXiangyi Company); incubator (Binder Company). Dilution and storage of compounds: depending on solubility, the test compounds are prepared as stock solutions of 0.5-10 mmol/L with dimethyl sulphoxide (DMSO), and aliquots of the stock are stored at −20° C.;Preparation of working solution of the compounds: Before test, aliquots of the compounds are removed from the refrigerator, and diluted with pure DMSO to 50× of the level needed; and then the compounds are diluted with deionized water to 4× of the level needed;Preparation of 1.33× enzymatic buffer: 5× enzymatic buffer (from HTRF kit) is diluted to 1.33× with deionized water, and appropriate components of the final level 1.33× are added: 1.33 mmol/L dithiothreitol (DTT) and 1.33 mmol/L MgCl2;Preparation of kinase working solution: Met is diluted to 2× final level required, 0.2 ng/μL, with 1.33× enzymatic buffer;Preparation of substrate working solution: the substrate labeled with biotin (from HTRF kit) and ATP (10 mM) are diluted with 1.33× enzymatic buffer to prepare a mixture at 4× of the final level required;Preparation of the testing working solution: Streptavidin-XL665, 16.67 μmol/L is diluted with HTRF test buffer to 4× of the final level required, and then mixed with antibody-Cryptate of the same volume (both from the HTRF kit).Enzymatic reaction step: 4 μl of kinase working solution is added to each well of the low volume 384-well plate. Meanwhile, 4 μL 1.33× enzymatic buffer is added as the negative control. 2 μL compound working solution is added into each well, and 2 μL 8% DMSO in water is added as zero compound level control (i.e., positive control). At 25° C. (or 30 C), incubate for 5-10 min; add 2 μL substrate working solution into each well to initiate the enzymatic reaction. Allow to react while shaking at 25° C. (or 30° C.) for 15-60 min.
Measurement: IC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 552.54, ALogP 6.97, HBA 7, HBD 2, PSA 98.36, QED 0.22
Compound (SMILES): C[C@]1(O)CCN(C(=O)c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)C1
InChIKey: OJCCNWLOIVOTIV-WNSKOXEYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 488.51, ALogP 3.4, HBA 6, HBD 4, PSA 106.17, QED 0.45
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CN(C3CC3)C2)cc1)c1ccccc1
InChIKey: FYLMFZGXSLRZEH-IRWWKPKRSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 = 2526 nM (pChEMBL 5.599999904632568)
Descriptors: MW 425.57, ALogP 5.69, HBA 3, HBD 2, PSA 43.7, QED 0.46
Compound (SMILES): C[C@](O)(Cn1cc(F)cn1)C(=O)Nc1cnc(C#N)c(C(F)(F)F)c1
InChIKey: PLYZMJXXOPVZLJ-ZDUSSCGKSA-N
Target: Androgen receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P15207
Assay: Displacement of [3H]-MIB from wild-type rat AR LBD measured after 16 hrs by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 357.27, ALogP 1.7, HBA 6, HBD 2, PSA 103.83, QED 0.81
Compound (SMILES): CCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)O)C(C)C
InChIKey: NOKXPDPRVUBWSO-XBJFMILWSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293 cells co-expressing Rlucll-beta-arrestin2 assessed as induction of beta-arrestin2 recruitment to APJ incubated for 30 mins by BRET assay
Measurement: EC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 1262.53
Compound (SMILES): CCN1CC2(CCN(CCc3cc(F)ccc3F)CC2)O[C@H](C)C1=O
InChIKey: KALIKXMQWFLZKB-CQSZACIVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHOK1 cell membranes incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 352.43, ALogP 2.61, HBA 3, HBD 0, PSA 32.78, QED 0.84
Compound (SMILES): Cc1c[nH]nc1Nc1nc(Cl)nc2c1ncn2Cc1ccc(C(=O)Nc2ccccc2N)cc1
InChIKey: KXYKHEDMCUBQNA-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in baculovirus using fluorogenic peptide p53 residues 379-382 (RHKK(Ac)AMC) as substrate by Fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 473.93, ALogP 4.14, HBA 8, HBD 4, PSA 139.43, QED 0.21
Compound (SMILES): O=C1C[C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)CO1
InChIKey: MQEPWBMWFIVRPS-ZGSHZZHUSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of recombinant human PTP1B (1 to 322 residues) expressed in Escherichia coli using IR5 (1142 to 1153, pY1146) as substrate by malachite green dye based colorimetric assay
Measurement: IC50 = 5140 nM (pChEMBL 5.289999961853027)
Descriptors: MW 264.23, ALogP -2.88, HBA 8, HBD 4, PSA 125.68, QED 0.4
Compound (SMILES): O=c1ccoc2ccc(OCCCCCN3CCOCC3)cc12
InChIKey: CIQYOCMKRTYOTH-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 317.39, ALogP 2.67, HBA 5, HBD 0, PSA 51.91, QED 0.73
Compound (SMILES): CN1CCc2ccc(OCCCCN3CCN(c4cccc(C(F)(F)F)c4)CC3)cc2C1=O
InChIKey: NWSWBVKRQJZUCZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Receptor Binding Assay: D2:Procedures(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 Butaclamol (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-Spiperone 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 37° C. for 20 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.(6) The scintillation vials were put into Liquid Scintillation Counter for counting.Inhibition rate(I%)=(Total binding tube cpm−compound cpm)/(Total binding tube cpm−nonspecific binding tube cpm)×100% .
Measurement: Ki = 17.2 nM (pChEMBL 7.760000228881836)
Descriptors: MW 461.53, ALogP 4.31, HBA 4, HBD 0, PSA 36.02, QED 0.58
Compound (SMILES): C=CC(=O)N1CCN(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)CC1
InChIKey: LXGBKZHEQNMKJY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using ULight -mylein basic protein as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 2090 nM (pChEMBL 5.679999828338623)
Descriptors: MW 394.48, ALogP 2.26, HBA 5, HBD 2, PSA 94.22, QED 0.73
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccc(F)cc2)cc1
InChIKey: RNTJUUSYPCOMRZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 311.1 nM (pChEMBL 6.510000228881836)
Descriptors: MW 416.46, ALogP 1.04, HBA 5, HBD 4, PSA 147.46, QED 0.53
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CNC[C@@H](c3nnc4ccccn34)C2)nc1-c1c[nH]c2ccccc12
InChIKey: IJQBKJGUIDXXLI-LSDHHAIUSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 478.48, ALogP 4.24, HBA 7, HBD 3, PSA 95.82, QED 0.36
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CCN2CCN(c3ccccc3)CC2)cc1
InChIKey: GQFCMDDCGROQDX-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped-flow CO2 hydration assay
Measurement: Ki = 23.7 nM (pChEMBL 7.619999885559082)
Descriptors: MW 402.52, ALogP 1.16, HBA 5, HBD 2, PSA 95.74, QED 0.72
Compound (SMILES): COc1ccc(Cl)cc1-c1nn(C)cc1NC(=O)c1cncc2cn(C)nc12
InChIKey: FCWWZBZYMGWKGY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 396.84, ALogP 3.28, HBA 7, HBD 1, PSA 86.86, QED 0.57
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](Nc2ncnc3ccc(C(F)(F)F)cc23)C1=O
InChIKey: QAPTWHXHEYAIKG-RCOXNQKVSA-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 506.57, ALogP 3.48, HBA 6, HBD 3, PSA 99.25, QED 0.57
Compound (SMILES): O=C(NCc1ccccc1)c1ccc(S(=O)(=O)NCc2ccccc2)cc1
InChIKey: QDGVJMITKNOVTP-UHFFFAOYSA-N
Target: LIM domain kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53667
Assay: Affinity Biochemical interaction (RapidFire MS assay) EUB0000285b LIMK1
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 380.47, ALogP 3.1, HBA 3, HBD 2, PSA 75.27, QED 0.66
Compound (SMILES): COc1ccc(Nc2ncc(C(F)(F)F)c(NC3CC3)n2)cc1OC
InChIKey: BQROJYIEHOOQBY-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 354.33, ALogP 3.83, HBA 6, HBD 2, PSA 68.3, QED 0.82
Compound (SMILES): CN(C)CC/C=C/c1cccnc1
InChIKey: ZZHZSKGOOLOJFA-ZZXKWVIFSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]nicotine from 5-hydroxytryptamine receptor 1A (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 176.26, ALogP 2.05, HBA 2, HBD 0, PSA 16.13, QED 0.7
Compound (SMILES): C/C(=N\NC(N)=S)c1nnn(-c2ccc(S(=O)(=O)Nc3nccs3)cc2)c1C
InChIKey: RRKBFCHMSRWBJV-GIJQJNRQSA-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 436.55, ALogP 1.39, HBA 9, HBD 3, PSA 140.18, QED 0.3
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 299 nM (pChEMBL 6.519999980926514)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): CCN(CC)C(=O)Oc1ccc(/C=C/C(=O)N2CCc3ccccc3C2)cc1OC
InChIKey: XINGJGMSNDJSNH-ACCUITESSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate after 15 mins by Ellman's method
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 408.5, ALogP 4.13, HBA 4, HBD 0, PSA 59.08, QED 0.67
Compound (SMILES): C=CC(=O)N1CCC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2)CC1
InChIKey: VFRSDNYJPASDOG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Biochemical Assay for CDK12 (Kd Determination): Kinase-tagged T7 phage strains were grown in parallel in 24-well blocks in an E. coli host derived from the BL21 strain. E. coli were grown to log-phase and infected with T7 phage from a frozen stock (multiplicity of infection=0.4) and incubated with shaking at 32° C. until lysis (90-150 minutes). The lysates were centrifuged (6,000×g) and filtered (0.2 μm) to remove cell debris. The remaining kinases were produced in HEK-293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads were treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific phage binding. Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 40× stocks in 100% DMSO and directly diluted into the assay. All reactions were performed in polypropylene 384-well plates in a final volume of 0.02 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR.
Measurement: Kd = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 404.51, ALogP 4.22, HBA 3, HBD 2, PSA 78.09, QED 0.71
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCN(S(N)(=O)=O)CC3)cc2)nc2sccc12
InChIKey: WTHHTULGDNIPBZ-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 331 nM (pChEMBL 6.480000019073486)
Descriptors: MW 561.69, ALogP 4.71, HBA 9, HBD 2, PSA 137.47, QED 0.31
Compound (SMILES): Cc1cc(-c2cnc3[nH]cc(-c4ccncc4)c3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: ZMCCTUGKELKLJP-INIZCTEOSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using diclofenac as substrate measured after 5 to 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 408.51, ALogP 5.35, HBA 3, HBD 1, PSA 61.88, QED 0.49
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)c(Cl)c2sc(N[C@H]3CCCC[C@@H]3O)nc12
InChIKey: UTKUVLWIEWNEAC-RYUDHWBXSA-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 = 34254 nM (pChEMBL 4.460000038146973)
Descriptors: MW 435.94, ALogP 3.62, HBA 9, HBD 3, PSA 115.41, QED 0.54
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CCC2)c2cc(-c3ccc(C(F)(F)F)s3)cnc21
InChIKey: VBYDZMQKWHOANY-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.39, ALogP 2.71, HBA 6, HBD 0, PSA 60.13, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: VEGQLNMUJOVTKQ-AECWIZBESA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]deltorphin-II from human DOR expressed in CHO cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: Ki = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 1247.51
Compound (SMILES): C[C@@](O)(CS(C)(=O)=O)C(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: VIHNKLOUNODTJW-XWVZOOPGSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 677.63, ALogP 4.42, HBA 6, HBD 2, PSA 117.61, QED 0.33
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(-c3cccc(-c4ccccc4)c3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: MKRXYOLOOVOWQH-JYIZQLJCSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 2a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.033 nM (pChEMBL 10.479999542236328)
Descriptors: MW 897.05, ALogP 8.34, HBA 8, HBD 4, PSA 174.64, QED 0.09
Compound (SMILES): O=C(Nc1c[nH]nc1-c1cc(Cl)ccc1OC(F)F)c1cncc2scnc12
InChIKey: MURNDAWLFYCTAR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human JAK1 (854 to 1154 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay
Measurement: Ki = 0.51 nM (pChEMBL 9.289999961853027)
Descriptors: MW 421.82, ALogP 4.59, HBA 6, HBD 2, PSA 92.79, QED 0.49
Compound (SMILES): COc1ncc(-c2ccc3ncnc(Nc4cnn(CCO)c4)c3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: DUUVJFLCJKWQTO-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using lipid as substrate incubated for 15 mins followed by substrate addition and measured after 60 mins ADPGloTM reagent based assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 553.55, ALogP 3.71, HBA 10, HBD 3, PSA 144.15, QED 0.25
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)O
InChIKey: AJVDIBTZNDJXEE-JMHPHXCKSA-N
Target: Matrilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P09237
Assay: Inhibition of human MMP7 using 3163v as substrate preincubated for 15 mins followed by substrate addition and measured after 40 mins by fluorometric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1080.23