lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(CC)c1ccc(-c2cc(-c3ccc(C(=O)O)cc3)ccc2OCCCCO)cc1C(C)(C)C
InChIKey: MFJSSFBKCJUROC-UHFFFAOYSA-N
Target: Retinoic acid receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10826
Assay: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 489.66, ALogP 7.01, HBA 4, HBD 2, PSA 70, QED 0.28
Compound (SMILES): O=C(NCc1cccc(OCCCS(=O)(=O)N2CCCCC2C(=O)O)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: NEPHXSICDJEKLG-UHFFFAOYSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of recombinant human AMPA-activated MMP3 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 528.59, ALogP 1.89, HBA 7, HBD 3, PSA 158.76, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCC#Cc2ccccc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GYBMGGFXFSFXNL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.58, ALogP 5.63, HBA 7, HBD 0, PSA 65.3, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C(C)(C)C(=O)N5CCNCC5)c4)nc3c2)c1
InChIKey: RZRVTNNQCLYNOB-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 4265.8 nM (pChEMBL 5.369999885559082)
Descriptors: MW 555.68, ALogP 4.23, HBA 9, HBD 1, PSA 97.64, QED 0.33
Compound (SMILES): Nc1ncnc2cc(CN3C(=O)CN(S(=O)(=O)c4cc5ccc(Cl)cc5s4)CC3C(=O)O)ccc12
InChIKey: SXJRFJQQWDUBFI-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 30 min pre-incubation of enzyme with compound and 30 min reaction time after substrate addition.
Measurement: IC50 = 0.675 nM (pChEMBL 9.170000076293945)
Descriptors: MW 532, ALogP 2.57, HBA 8, HBD 2, PSA 146.79, QED 0.4
Compound (SMILES): Cc1cc(C(=O)Nc2nc3cccc(C)c3n2[C@@H]2CCCCN(C(=O)/C=C/CN(C)C)C2)ccn1
InChIKey: SKLAQDNYYXAFGK-QWDXWUACSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 474.61, ALogP 3.97, HBA 6, HBD 1, PSA 83.36, QED 0.55
Compound (SMILES): CC(C)[C@@H]1c2nn(-c3cccc(S(C)(=O)=O)c3)cc2CN1c1cc(C(F)(F)F)ncn1
InChIKey: OMMCNHJJHLQJHQ-LJQANCHMSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 451.47, ALogP 3.8, HBA 7, HBD 0, PSA 80.98, QED 0.6
Compound (SMILES): COc1cn(C(C)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: MPSQYCLTAAEIDL-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 451.87, ALogP 3.95, HBA 6, HBD 2, PSA 121.42, QED 0.58
Compound (SMILES): Cc1cc(Cl)ccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)ccc21
InChIKey: OAHDIZLUMALIAR-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: In Vitro Assay: HEK 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the IonWorks® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, Calif.). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation. Cells were held at −110 mV for three seconds (Nav 1.7) or half a second (Nav 1.5) from a holding voltage of −15 mV, then put through a series of 26 pulses of 150 msec duration to −20 mV at a frequency of 5 Hz. Cells were then left unclamped for a period of 3 to 8 minutes while a single concentration of test compound was added. Cells were then reclamped and put through the same voltage protocol. Current at the end of the 26th pulse to −20 mV was subtracted from the peak current evoked by the 26th pulse to −20 mV to correct for leak current.
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 421.93, ALogP 4.44, HBA 6, HBD 1, PSA 71.53, QED 0.67
Compound (SMILES): CO[C@H]1C[C@@H](n2c(=O)n(C)c3cnc4ccc(-c5ccc(OCCCN6CCCCC6)nc5)cc4c32)C1
InChIKey: QBXNJMCSVGEQDI-ZRZAMGCNSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology assay
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 501.63, ALogP 4.55, HBA 8, HBD 0, PSA 74.41, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC[C@H](C#N)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NTCROAMSHNBTJA-LJQANCHMSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.58, ALogP 4.03, HBA 9, HBD 0, PSA 92.33, QED 0.37
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2cccc(CS(C)(=O)=NC#N)c2)ncc1F
InChIKey: PMIUHCUGSNZOBV-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: CDK2/CycE Kinase Assay: Recombinant fusion proteins of GST and human CDK2 and of GST and human CycE, expressed in insect cells (Sf9) and purified by Glutathion-Sepharose affinity chromatography, were purchased from ProQinase GmbH (Freiburg, Germany). As substrate for the kinase reaction biotinylated peptide biotin-Ttds-YISPLKSPYKISEG (C-terminus in amid form) was used which can be purchased e.g. form the company JERINI Peptide Technologies (Berlin, Germany)For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of CDK2/CycE in aqueous assay buffer [50 mM Tris/HCl pH 8.0, 10 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium ortho-vanadate, 0.01% (v/v) Nonidet-P40 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 429.45, ALogP 4.25, HBA 7, HBD 1, PSA 100.26, QED 0.59
Compound (SMILES): COc1cc(N2CCC[C@@H](O)C2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: ASBGJVNBZBSENK-RUZDIDTESA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 647.69, ALogP 6.7, HBA 9, HBD 3, PSA 116.91, QED 0.17
Compound (SMILES): NCC1CCN(c2ccc(Cl)cc2NC(=O)c2cnn3cccnc23)CC1
InChIKey: ITDPQZHRPNERLI-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51617
Assay: In vitro IRAK-1 and IRAK-4 Assay: Purified recombinant IRAK-4 protein was incubated with 250 uM synthetic peptide(KKARFSRFAGSSPSQSSMVAR) in 30 ul of kinase buffer including (20 mM MOPS pH7.2, 25 mM beta glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM DTT, 50 uM ATP, 20 mM MgCl2, 10 uCi gamma-33P, 0.1% BSA) for the indicated time. For purified recombinant IRAK-1 protein kinase assay, 50 uM ATP was used. A 25 ul aliquot of the reaction mixture was transferred on to p81 phosphocellulose squares (Upstate Biotechnology, Lake Placid, N.Y.). The assay squares were washed three times with 0.75% phosphoric acid and once with acetone. Enzyme activity was measured by determining the bound radioactivity by liquid scintillation counting.
Measurement: IC50 = 463 nM (pChEMBL 6.329999923706055)
Descriptors: MW 384.87, ALogP 2.81, HBA 6, HBD 2, PSA 88.55, QED 0.72
Compound (SMILES): COc1cc(OC)cc(N(CCNCCF)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SHMLFYDRRWCODZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 450.52, ALogP 3.74, HBA 8, HBD 1, PSA 77.33, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(Cc2cccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XVHQBHLEUMQQIV-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 482.54, ALogP 4.79, HBA 9, HBD 0, PSA 87.42, QED 0.31
Compound (SMILES): CC(C)(O)c1cn(-c2ccc(-c3ccc(CO)c(S(C)(=O)=O)c3)cc2)c(Cc2ccccc2Cl)n1
InChIKey: VVVMBZVHNIYCQS-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXR-beta in human whole blood assessed as ABCA1 gene induction by measuring ABCA1 mRNA level after 4 hrs by SYBR-Green dye-based Q-PCR analysis
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 511.04, ALogP 4.91, HBA 6, HBD 2, PSA 92.42, QED 0.37
Compound (SMILES): COc1ccn2c(-c3ccnc(Nc4cccc(OCCN(C)C)c4)n3)c(-c3cccc(C(=O)Nc4ccc(F)cc4F)c3)nc2c1
InChIKey: OEQAHCYBQYJMNG-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 635.67, ALogP 6.68, HBA 9, HBD 2, PSA 105.91, QED 0.16
Compound (SMILES): N#CCC1(n2ccc(-c3ncnc4[nH]ccc34)c2)CN(C2CCN(C(=O)Nc3ccc(F)cc3Cl)CC2)C1
InChIKey: GMXLGWFJLRXYLE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 533.01, ALogP 4.84, HBA 6, HBD 2, PSA 105.87, QED 0.38
Compound (SMILES): CN(C)CCCOc1ccc(-c2ccc3ncc4c(c3c2)n(C2CCOCC2)c(=O)n4C)cn1
InChIKey: AOTRIQLYUAFVSC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 461.57, ALogP 3.63, HBA 8, HBD 0, PSA 74.41, QED 0.39
Compound (SMILES): COc1cc(CS(C)(=N)=O)cc(Nc2ncc(F)c(-c3ccc(F)cc3OC)n2)c1
InChIKey: NYJBTSYJXIHYOP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: CDK2/CycE Kinase Assay: Recombinant fusion proteins of GST and human CDK2 and of GST and human CycE, expressed in insect cells (Sf9) and purified by Glutathion-Sepharose affinity chromatography, were purchased from ProQinase GmbH (Freiburg, Germany). As substrate for the kinase reaction biotinylated peptide biotin-Ttds-YISPLKSPYKISEG (C-terminus in amid form) was used which can be purchased e.g. form the company JERINI Peptide Technologies (Berlin, Germany)For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of CDK2/CycE in aqueous assay buffer [50 mM Tris/HCl pH 8.0, 10 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium ortho-vanadate, 0.01% (v/v) Nonidet-P40 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 434.47, ALogP 4.36, HBA 7, HBD 2, PSA 97.19, QED 0.57
Compound (SMILES): Cc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1
InChIKey: YSVWQQHBTPMQMR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 298.39, ALogP 3.12, HBA 3, HBD 1, PSA 45.33, QED 0.89
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(N(C)C)no1
InChIKey: QJMKYRIHQWAKSM-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 461.31, ALogP 4.72, HBA 9, HBD 1, PSA 98.43, QED 0.42
Compound (SMILES): COC(=O)c1ccccc1S(=O)(=O)Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4C(=O)OC)ccc3o2)cc1
InChIKey: PQMJLPWTRFOANC-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 621.65, ALogP 4.67, HBA 10, HBD 2, PSA 170.97, QED 0.22
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc2ccc([C@H]3CC[C@H](c4ccc5nc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c5c4)N3c3ccc(C(C)(C)C)cc3)cc2[nH]1)C(C)C
InChIKey: NREDIDBJPFQPKQ-UEECLIOXSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1b (isolate Con1) (HCV)
UniProt: Q9WMX2
Assay: Inhibition of NS5A in HuH7 cell infected HCV genotype 1b Con1 assessed as decrease in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.013 nM (pChEMBL 10.890000343322754)
Descriptors: MW 888.13, ALogP 8.91, HBA 9, HBD 4, PSA 177.88, QED 0.1
Compound (SMILES): N[C@H](C(=O)O)C(NS(=O)(=O)c1ccc(Cl)cc1)C(=O)O
InChIKey: PHSLITQWZPTNLO-JAMMHHFISA-N
Target: Excitatory amino acid transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P43003
Assay: Inhibition of [3H]-D-Asp uptake at human EAAT1 expressed in HEK293 cells measured after 3 mins by TopCount method
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 322.73, ALogP -0.52, HBA 5, HBD 4, PSA 146.79, QED 0.55
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nnn(Cc5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: INSJPGRKOSFBIE-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 4a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 629.65, ALogP 4.95, HBA 8, HBD 1, PSA 127.4, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(N)=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: UIUUIHADIPAKSK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 0.8913 nM (pChEMBL 9.050000190734863)
Descriptors: MW 475.55, ALogP 2.65, HBA 9, HBD 2, PSA 120.42, QED 0.32
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1O[C@@H]1C[C@H]2OC[C@H](OC)[C@H]2O1
InChIKey: HDJUYMWWZOHAHK-WKRCXCSHSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 540.77, ALogP 4.84, HBA 8, HBD 1, PSA 83.96, QED 0.44
Compound (SMILES): COc1cc(-c2cn(C)nc2C)ccc1Nc1ncc2ccnc(NCC(C)(C)C)c2n1
InChIKey: LEVJITMIUUMAFY-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of full length human N-terminal His-tagged CDK2/cyclinA expressed in baculovirus expression system using 5FAM- peptide18 as substrate after 60 mins by caliper assay
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 431.54, ALogP 4.94, HBA 8, HBD 2, PSA 89.78, QED 0.45
Compound (SMILES): CNCc1ccc(Cl)c(-c2ccccc2OC)c1
InChIKey: NSASZAUFRUOUIN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Agonist activity at 5-HT7R (unknown origin) transfected in HEK293 cells expressing tTA-dependent luciferase reporter and beta arrestin 2-TEV fusion gene assessed as beta arrestin recruitment incubated for 22 hrs by Tango assay
Measurement: EC50 = 147.91 nM (pChEMBL 6.829999923706055)
Descriptors: MW 261.75, ALogP 3.74, HBA 2, HBD 1, PSA 21.26, QED 0.91
Compound (SMILES): Cc1noc(C)c1S(=O)(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: CHQKZKZKVPCOPD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 521.61, ALogP 2.2, HBA 10, HBD 1, PSA 149.83, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(CCS(C)(=O)=O)c4)nc3c2)c1
InChIKey: MDGGVKPYDJLWOU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 497.58, ALogP 2.69, HBA 10, HBD 1, PSA 119.67, QED 0.35
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc(OC)c4nnn(Cc5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: YQSZHQDSWAVRIF-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 4a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 659.67, ALogP 4.96, HBA 9, HBD 1, PSA 136.63, QED 0.24
Compound (SMILES): CNCCN(c1cc(OC)cc(OCCO)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1.Cl
InChIKey: XRWLZQITSKSQMM-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.53, ALogP 2.77, HBA 9, HBD 2, PSA 97.56, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(N3C[C@@H](C)O[C@@H](C)C3)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: MWQJFJHGPDMTDO-MEVFMXSASA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 585.75, ALogP 4.76, HBA 10, HBD 0, PSA 81.01, QED 0.26
Compound (SMILES): Nc1nc2cc(-c3cn(C4CCOCC4)c4ncnc(N)c34)ccc2o1
InChIKey: IYXWKNZOERXTKV-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 350.38, ALogP 2.76, HBA 8, HBD 2, PSA 118.01, QED 0.57
Compound (SMILES): Cc1cccc(-c2cc(Nc3nn(C)cc3C)nc3[nH]cc(C#N)c23)n1
InChIKey: BGDVHDMLORIBJR-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: LanthaScreen Kinase Activity Assay: In the assay, 1 nM LRRK2 WT or 250 pM LRRK2 G2019S kinase is incubated with the test compound (typically at 0 to 30 μM) for 30 minutes before the kinase reaction is initiated by addition of 1.3 mM ATP and 0.4 μM fluorescein-LRRKtide. The reaction mixture (20 μl total volume) is incubated for 2 hours at 30° C. before the reaction is terminated by addition of 10 mM EDTA and 1 nM terbium-labelled anti-phospho-LRRKtide antibody (final volume 20 μl). The mixture is further incubated for 30 minutes at RT. TR-FRET is measured by excitation of the terbium-donor with 340 nm light and subsequent (delay time 100 μs) measurement of terbium and fluorescein emission at 495 nm and 520 nm, respectively, over a time window of 1000 μs. The measurement is repeated 10 times for fluorescein and 10 times for terbium emission with a 2000 μs time window between repeats. TR-FRET measurements are performed on a Biomek Synergy plate. The TR-FRET signal is calculated as the emission-ratio at 520 nm over 495 nm.
Measurement: EC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 343.39, ALogP 3.59, HBA 6, HBD 2, PSA 95.21, QED 0.59
Compound (SMILES): O=C(Nc1ccc(-n2ccccc2=O)cc1F)[C@H]1Cc2ccccc2CN1C(=O)Nc1ccc(Cl)cn1
InChIKey: IUGUGRHPIJNBDF-HSZRJFAPSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 30 min pre-incubation of enzyme with compound and 30 min reaction time after substrate addition.
Measurement: IC50 = 0.696 nM (pChEMBL 9.15999984741211)
Descriptors: MW 517.95, ALogP 4.62, HBA 5, HBD 2, PSA 96.33, QED 0.41
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(C#N)cc3Cl)CC2)C1
InChIKey: YUBFUSWKFUFHHX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 540.03, ALogP 4.57, HBA 7, HBD 2, PSA 129.66, QED 0.38
Compound (SMILES): O=S(=O)(NCc1ccco1)c1ccc(Nc2ccc(F)cc2F)cc1C(F)(F)F
InChIKey: IVLALHAWSBHIRR-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: IC50 = 1176 nM (pChEMBL 5.929999828338623)
Descriptors: MW 432.37, ALogP 4.8, HBA 4, HBD 2, PSA 71.34, QED 0.55
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3cccc(Oc4ccccc4)c3)CC2)C1
InChIKey: YUJWHVPMAKCLQL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 544.66, ALogP 5.2, HBA 8, HBD 1, PSA 98.89, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(O)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: ISVOAPUXDBEYPJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 474.57, ALogP 3.25, HBA 9, HBD 1, PSA 88.77, QED 0.42
Compound (SMILES): O=C(NCCS(=O)(=O)Nc1ccc(-n2ccncc2=O)cc1)c1ccc(Cl)s1
InChIKey: YSWODTNWYVODPG-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 30 min pre-incubation of enzyme with compound and 45 min reaction time after substrate addition.
Measurement: IC50 = 32.9 nM (pChEMBL 7.480000019073486)
Descriptors: MW 438.92, ALogP 2.12, HBA 7, HBD 2, PSA 110.16, QED 0.59
Compound (SMILES): Cc1ccc2c(c1)C(=O)N(C)c1cnc(Nc3cccc(S(=O)(=O)N4CCC(O)CC4)c3)nc1N2C
InChIKey: GHKMIOAEPALCFS-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora kinase B (D25 to A303 residues) expressed in mammalian expression system by Z'LYTE assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 508.6, ALogP 3.03, HBA 8, HBD 2, PSA 118.97, QED 0.55
Compound (SMILES): O=C(O)C1CN(Cc2ccc3c(c2)CCc2c-3noc2-c2onc(-c3ccccc3)c2C(F)(F)F)C1
InChIKey: IVRVCMWFTIBONM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at human S1P1 assessed as stimulation of cAMP accumulation
Measurement: EC50 = 0.032 nM (pChEMBL 10.489999771118164)
Descriptors: MW 495.46, ALogP 5.3, HBA 6, HBD 1, PSA 92.6, QED 0.4
Compound (SMILES): CCCn1cc(-c2cnc3ccc(N(CCN)c4cc(OC)cc(OC)c4)cc3n2)cn1.Cl
InChIKey: FYIRHIZOHYRDDH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.514 nM (pChEMBL 8.819999694824219)
Descriptors: MW 432.53, ALogP 4.02, HBA 8, HBD 1, PSA 91.32, QED 0.43
Compound (SMILES): C=C(C)c1cc(-c2cc(NC(=O)c3cccc(C(F)(F)F)c3)ccc2C)nc(N2CCOCC2)n1
InChIKey: NZQDZMBWHLVRCS-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Enzyme Assay: Final assay conditions were 4 pM cRaf, 3 uM ATP, 10 nM biotin tagged MEK1 kinase dead protein substrate. Reactions were performed in Greiner384 well plates, catalog #784075. Reaction buffer was 50 mM Tris, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 0.01% Tween-20, 0.05% BSA and 1 mM DTT. 5 ul of 2×cRaf plus MEK1 were dispensed into plates containing 0.25 ul of compound in 100% DMSO and incubated at room temperature for 30 minutes. Reactions were started by addition of 5 ul of 2×ATP. Reactions were run for two hours and terminated by addition of 10 ul of 2× antibody and Alphascreen bead mixture in Stop Buffer. Stop Buffer was 50 mM Tris, pH 7.5, 0.005% Tween-20, 25 mM EDTA.
Measurement: IC50 = 0.137 nM (pChEMBL 9.859999656677246)
Descriptors: MW 482.51, ALogP 5.59, HBA 5, HBD 1, PSA 67.35, QED 0.51
Compound (SMILES): CC(=O)N1CCc2[nH]nc(Nc3ccccc3)c2C1
InChIKey: ZXIJCVCJLDGJRX-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Displacement of biotinylated ligand from recombinant His-tagged BRPF1 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 256.31, ALogP 2.06, HBA 3, HBD 2, PSA 61.02, QED 0.86
Compound (SMILES): CC(C)[C@@H]1c2nn(-c3cccc(S(C)(=O)=O)c3)cc2CN1c1nccc(C(F)(F)F)n1
InChIKey: WZQNVHXAZPMTQI-GOSISDBHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 2110 nM (pChEMBL 5.679999828338623)
Descriptors: MW 451.47, ALogP 3.8, HBA 7, HBD 0, PSA 80.98, QED 0.6
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2CO1
InChIKey: REMMHMJADZNMGO-KBPBESRZSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 493.37, ALogP 5.07, HBA 7, HBD 1, PSA 68.74, QED 0.48
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(OC)ncn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SDIZOFZVSQJIHJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 70.79 nM (pChEMBL 7.150000095367432)
Descriptors: MW 507.55, ALogP 4.04, HBA 10, HBD 0, PSA 100.31, QED 0.3
Compound (SMILES): O=C(Nc1cccc(C(F)(F)F)c1)N1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: YSEXRGLTJSGRFZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 429.41, ALogP 4.04, HBA 5, HBD 2, PSA 91.21, QED 0.5
Compound (SMILES): [2H]C([2H])([2H])n1cc(-c2ccc3ncc(N(CCO)c4cc(OC)cc(OC)c4)nc3c2)cn1
InChIKey: XBRAGXSHNWCDEC-FIBGUPNXSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.818 nM (pChEMBL 8.550000190734863)
Descriptors: MW 405.46, ALogP 3.18, HBA 8, HBD 1, PSA 85.53, QED 0.51
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(N2CCN(C)CC2)no1
InChIKey: UNVZWJFKXAEDKM-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 516.39, ALogP 4.4, HBA 10, HBD 1, PSA 101.67, QED 0.38
Compound (SMILES): CCOc1cc(F)ccc1-c1nc(Nc2cc(F)cc(CS(C)(=N)=O)c2)ncc1F
InChIKey: XOTQSFMYDHXIOI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: CDK9/CycT1 : Recombinant full-length His-tagged human CDK9 and CycT1, expressed in insect cells and purified by Ni-NTA affinity chromatography, were purchase from Invitrogen (Cat. No PV4131). As substrate for the kinase reaction biotinylated peptide biotin-Ttds-YISPLKSPYKISEG (C-terminus in amid form) was used which can be purchased e.g. form the company JERINI peptide technologies (Berlin, Germany) For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of CDK9/CycT1 in aqueous assay buffer [50 mM Tris/HCl pH 8.0, 10 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium ortho-vanadate, 0.01% (v/v) Nonidet-P40 (Sigma)] were added and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 436.46, ALogP 4.88, HBA 6, HBD 2, PSA 87.96, QED 0.55
Compound (SMILES): COc1cc2c(cc1OC)CN(CCCCc1nc3cc(Cl)ccc3s1)CC2.Cl
InChIKey: CIEYQJXJQBPJAX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor by liquid scintillation counting method
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 416.97, ALogP 5.35, HBA 5, HBD 0, PSA 34.59, QED 0.49
Compound (SMILES): N#CCC1(n2cc(-c3c(C#N)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3c(F)cc(C#N)cc3F)CC2)C1
InChIKey: FSKSWJIKOXAUAG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 551.56, ALogP 3.68, HBA 8, HBD 1, PSA 141.42, QED 0.4
Compound (SMILES): CCC(=O)N1CCc2[nH]nc(-c3ccccc3)c2C1
InChIKey: DVIQMCGALYMKFG-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human His10-tagged BRD4 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 using 1% DMSO by SPR assay
Measurement: Kd = 31300 nM (pChEMBL 4.5)
Descriptors: MW 255.32, ALogP 2.37, HBA 2, HBD 1, PSA 48.99, QED 0.9
Compound (SMILES): CCC(=O)N1CC[C@H](Oc2ncnc3ccc(-c4cnc(OC)c(C#N)c4)cc23)C1
InChIKey: FCRWAGMUQQHCJF-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of myristoylated PI3K-alpha (unknown origin) overexpressed in Rat1 cells assessed as inhibition of Akt phosphorylation
Measurement: IC50 = 1380 nM (pChEMBL 5.860000133514404)
Descriptors: MW 403.44, ALogP 2.96, HBA 7, HBD 0, PSA 101.23, QED 0.65
Compound (SMILES): CCN1CCCC(c2nc(COc3cc4ncnc(Nc5ccc(Cl)c(Cl)c5)c4cc3OC)no2)C1
InChIKey: GCBUMMPSFVNQKY-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 529.43, ALogP 5.85, HBA 9, HBD 1, PSA 98.43, QED 0.3
Compound (SMILES): O=C(NCc1cccc(OCCCS(=O)(=O)N2CCCCC2C(=O)O)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: NEPHXSICDJEKLG-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of recombinant human AMPA-activated MMP1 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.59, ALogP 1.89, HBA 7, HBD 3, PSA 158.76, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCC#Cc2ccccc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GYBMGGFXFSFXNL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 489.58, ALogP 5.63, HBA 7, HBD 0, PSA 65.3, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C(C)(C)C(=O)N5CCNCC5)c4)nc3c2)c1
InChIKey: RZRVTNNQCLYNOB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 18.62 nM (pChEMBL 7.730000019073486)
Descriptors: MW 555.68, ALogP 4.23, HBA 9, HBD 1, PSA 97.64, QED 0.33
Compound (SMILES): Nc1ncnc2cc(CN3C(=O)CN(S(=O)(=O)c4cc5ccc(Cl)cc5s4)CC3C(=O)O)ccc12
InChIKey: SXJRFJQQWDUBFI-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 30 min pre-incubation of enzyme with compound and 45 min reaction time after substrate addition.
Measurement: IC50 = 0.712 nM (pChEMBL 9.149999618530273)
Descriptors: MW 532, ALogP 2.57, HBA 8, HBD 2, PSA 146.79, QED 0.4
Compound (SMILES): CC(C)[C@@H]1c2nn(-c3cccc(S(C)(=O)=O)c3)cc2CN1c1cc(C(F)(F)F)ncn1
InChIKey: OMMCNHJJHLQJHQ-LJQANCHMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 5210 nM (pChEMBL 5.28000020980835)
Descriptors: MW 451.47, ALogP 3.8, HBA 7, HBD 0, PSA 80.98, QED 0.6