lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(CC(F)(F)F)C[C@H]1CC[C@H](N2CNC(=O)c3cnc4[nH]ccc4c32)CC1
InChIKey: IRUHHPCRGFKYOZ-JOCQHMNTSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: The inhibitory activity of the compounds of the present invention against JAK was measured.The respective enzymes (JAK1, JAK2, JAK3 and Tyk2) were purchased from Carna Biosciences, Inc.As a substrate of the enzymes (hereinafter referred to as substrate), LANCE Ultra ULight-JAK-1 (Tyr1023) Peptide (manufactured by PerkinElmer Inc.) was used.As an antibody for detecting phosphorylation of the substrate, LANCE Ultra Europium-anti-phospho tyrosine antibody (PT66) (manufactured by PerkinElmer Inc.) was used.The other reagents were purchased from the following.Adenosine triphosphate (ATP): Sigma-Aldrich4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES): DOJINDO LABORATORIESGlycol ether diamine tetraacetic acid (EGTA): DOJINDO LABORATORIES Magnesium chloride (MgCl2): Wako Pure Chemical Industries, Ltd.Dithiothreitol (DTT): Wako Pure Chemical Industries, Ltd.Tween 20: Sigma-AldrichEthylenediaminetetraacetic acid (EDTA): DOJINDO LABORATORIESThe compounds of the present invention, the enzymes (JAK1, JAK2, JAK3 and Tyk2), the substrate and ATP were used for assay as diluted with assay buffer.Â  As the assay buffer, one having the following composition was used.Â  HEPES (pH7.5): 50 mM EGTA: 1 mM MgCl2: 10 mM DTT: 2 mM Tween 20: 0.01% (wt/wt). The dilute concentration and the addition amount on a well plate as described hereinafter were adjusted so that the following final concentrations were achieved on the well plate.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 395.43, ALogP 3.12, HBA 4, HBD 2, PSA 64.26, QED 0.84
Compound (SMILES): CCS(=O)(=O)NC1CCCc2c(-c3ccc4c(c3)CCC(=O)N4C)cncc21
InChIKey: LVDKZTHQIJVVBW-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Cellular Enzyme Assay: The expression plasmids contains the ORF for either human/cyno CYP11B1 or CYP11B2 under the control of a suitable promoter (CMV-promoter) and a suitable resistance marker (neomycin). Using standard techniques the expression plasmid is transfected into G-402 cells and these cells are then selected for expressing the given resistance markers. Individual cell-clones are then selected and assessed for displaying the desired enzymatic activity using 11-Deoxycorticosterone (Cyp11B2) or 11-Deoxycortisol (Cyp11B1) as a substrate. G-402 cells expressing CYP11 constructs were established as described above and maintained in McCoy's 5a Medium Modified, ATCC Catalog No. 30-2007 containing 10% FCS and 400 μg/ml G418 (Geneticin) at 37° C. under an atmosphere of 5% CO2/95% air. Cellular enzyme assays were performed in DMEM/F12 medium containing 2.5% charcoal treated FCS and appropriate concentration of substrate (0.3-10 μM 11-Deoxycorticosterone, 11-Deoxycortisol or Corticosterone). For assaying enzymatic activity, cells were plated onto 96 well plates and incubated for 16 h. An aliquot of the supernatant is then transferred and analyzed for the concentration of the expected product (Aldosterone for CYP11B2; Cortisol for CYP11B1). The concentrations of these steroids can be determined using HTRF assays from CisBio analyzing either Aldosterone or Cortisol.
Measurement: EC50 = 4920 nM (pChEMBL 5.309999942779541)
Descriptors: MW 399.52, ALogP 2.97, HBA 4, HBD 1, PSA 79.37, QED 0.86
Compound (SMILES): CN(C)Cc1cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c(F)c(C(F)(F)F)n1
InChIKey: FEFBBJITSXZSDF-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 610.62, ALogP 3.67, HBA 9, HBD 1, PSA 122.86, QED 0.31
Compound (SMILES): CC(N)C/C=C\c1ccccc1
InChIKey: LLHJXESMOGGFAI-UITAMQMPSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C receptor expressed in HEK293 cells assessed as induction of calcium mobilization incubated for 15 mins by calcium 5 dye-based fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 161.25, ALogP 2.44, HBA 1, HBD 1, PSA 26.02, QED 0.72
Compound (SMILES): N#CC(C#N)C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: LSTAISHIPVMJJD-AULYBMBSSA-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.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 319.37, ALogP 2.93, HBA 6, HBD 1, PSA 106.45, QED 0.8
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCCN(C)C2)n1
InChIKey: STKWUQHKDUWIGO-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 530.48, ALogP 6.53, HBA 8, HBD 1, PSA 72.4, QED 0.29
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc([C@@H]2CCCN2C)n1
InChIKey: QHTZGTDGFHTCOG-FQEVSTJZSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 516.45, ALogP 6.49, HBA 8, HBD 1, PSA 72.4, QED 0.3
Compound (SMILES): c1cc2c(ncn3nnc([C@H]4CC[C@H](CN5CCC5)CC4)c23)[nH]1
InChIKey: LLLVLSAIMOMGRB-JOCQHMNTSA-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.
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 310.41, ALogP 2.59, HBA 5, HBD 1, PSA 62.11, QED 0.81
Compound (SMILES): COc1cc(N2CCC(N3CCN4CCOC[C@@H]4C3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: UBSJNJUTXOQWOY-HKBQPEDESA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 801.9, ALogP 6.73, HBA 12, HBD 2, PSA 121.62, QED 0.15
Compound (SMILES): C[C@H](NC(=O)C(=O)Nc1cc(C(F)(F)F)ccc1N1CCOCC1)C(=O)N[C@@H](CC(=O)O)C(=O)COP(=O)(c1ccccc1)c1ccccc1
InChIKey: KYGIHIZEIRIHFR-LVXARBLLSA-N
Target: Caspase-8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14790
Assay: Inhibition of recombinant MCH5 (unknown origin) pre-incubated for 60 mins with Acetyl-Tyr-Val-Ala-Asp-amino-4-methylcoumarin substrate followed by enzyme addition by fluorescence based assay
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 718.62, ALogP 2.46, HBA 9, HBD 4, PSA 180.44, QED 0.15
Compound (SMILES): CC[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(F)c2c(=O)n1-c1cccc(CC(F)(F)F)c1
InChIKey: JSFCONAGIRFNEB-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Homogeneous Time Resolved Fluorescence Assay: The ability of the compounds of the present invention to inhibit the activity of four PI3K isoforms, PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, were determined using a commercially available lipid kinase assay run in Homogeneous Time Resolved Fluorescence (HTRF) format. Assay DescriptionAssay principle: The PIP3 product is detected by displacement of biotin-PIP3 from an energy transfer complex consisting of Europium labeled anti-GST monoclonal antibody, a GST-tagged pleckstrin homology (PH) domain, biotinylated PIP3 and Streptavidin-Allophycocyanin (APC). Excitation of Europium in the complex results in an energy transfer to the APC and a fluorescent emission at 665 nm. The PIP3 product formed by PI 3-Kinase(h) activity displaces biotin-PIP3 from the complex resulting in a loss of energy transfer and thus a decrease in signal.This is a 3-step reaction: First, the kinase reaction with PIP2 substrate is carried out in the presence of ATP, and the reaction is quenched.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 497.46, ALogP 4.86, HBA 7, HBD 2, PSA 101.38, QED 0.33
Compound (SMILES): COc1cc(N2CCC(N3CCN(CCF)CC3)CC2)c(OC)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: MSXIHRKCKUXFBK-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 791.88, ALogP 7.31, HBA 11, HBD 2, PSA 112.39, QED 0.13
Compound (SMILES): O=C(/C=C/CN1CCCCC1)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cn1
InChIKey: YBEIPHUFRFGXCJ-SNAWJCMRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Irreversible inhibition of full length human ERBB1 autophosphorylation transfected in EGF-stimulated mouse NIH/3T3 cells incubated for 2 hrs followed by stimulation with EGF for 10 mins
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 440.91, ALogP 4.54, HBA 6, HBD 2, PSA 83.04, QED 0.55
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3cccnc3OC)nc3cc(C)ccn23)c(C#Cc2ccc3c(ccc(=O)n3C)c2)n1
InChIKey: BLCOQEHXRZDQMH-QFIPXVFZSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 597.68, ALogP 4.57, HBA 9, HBD 2, PSA 115.44, QED 0.27
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(C(=O)N(C)C)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)nccc2c1
InChIKey: RAHPBFRSLVDBER-AFJIDDCJSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of alpha-thrombin (unknown origin) using pyroGlu-Pro-Arg-pNA as substrate assessed as release of pNA after 10 to 120 mins by spectrophotometric method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 580.69, ALogP 5.3, HBA 7, HBD 3, PSA 129.89, QED 0.3
Compound (SMILES): Cc1ccnc(-c2cc(Nc3nn(C)cc3Cl)nc3[nH]cc(C#N)c23)c1
InChIKey: CBDJPXSHMIUPAJ-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 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 363.81, ALogP 3.94, HBA 6, HBD 2, PSA 95.21, QED 0.57
Compound (SMILES): COc1cncc(-c2nc3ccc(F)cn3c2C2CC2)c1
InChIKey: JQZNZPQADFOCLV-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1-8C7 expressed in Chinese hamster V79 cells using 11-deoxycortisol as substrate preincubated for 1 hr followed by substrate addition measured after 3 hrs by HTRF assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 283.31, ALogP 3.42, HBA 4, HBD 0, PSA 39.42, QED 0.74
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc3c(cc12)OCCO3
InChIKey: BWFXWPBHQAEGKO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
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 342.4, ALogP 2.58, HBA 5, HBD 1, PSA 63.79, QED 0.87
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COC(=O)[C@H](C)N)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: WRANVYZNSQCCSO-XVHYEQEESA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Functional Assay: Functional [35S]GTPgammaS binding assays were conducted as follows. kippa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 ug/ul kippa membrane protein (in-house), 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]GTPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 ul/well) was transferred to 96-shallow well polypropylene plates containing 10 ul of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25° C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Perkin Elmer, Shelton, Conn.) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 2001 ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50° C. for 2-3 hours.
Measurement: EC50 = 335.42 nM (pChEMBL 6.46999979019165)
Descriptors: MW 482.62, ALogP 2.81, HBA 7, HBD 1, PSA 83.25, QED 0.6
Compound (SMILES): Cc1cc(OC2CCNCC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: MQIAKZLWCNEYGB-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 631.69, ALogP 7.17, HBA 8, HBD 3, PSA 105.47, QED 0.16
Compound (SMILES): O=C(CCCCCCn1cc(-c2ccc3ncnc(Nc4cccc(Cl)c4F)c3c2)nn1)NO
InChIKey: PCKCQQLBJXBCNU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type EGFR (unknown origin) assessed as remaining ATP level measured after 15 mins by luminescence analysis
Measurement: IC50 = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 483.94, ALogP 4.88, HBA 8, HBD 3, PSA 117.85, QED 0.17
Compound (SMILES): CC(C)(C)c1ccc(N2CCN(c3nnc(Cc4ccc(F)cc4)c4c3CCCC4)CC2)cc1
InChIKey: OORARZMIZIGXRP-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 458.63, ALogP 5.71, HBA 4, HBD 0, PSA 32.26, QED 0.5
Compound (SMILES): COc1cc(C#N)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WMYLESPXATZBNH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (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 410.48, ALogP 4.46, HBA 7, HBD 0, PSA 79.86, QED 0.47
Compound (SMILES): CCC(=O)NC1CCCc2c(-c3cc4c(cc3F)N(C)C(=O)CC4)cncc21
InChIKey: CIRJNKSQEGVMOH-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Cellular Enzyme Assay: The expression plasmids contains the ORF for either human/cyno CYP11B1 or CYP11B2 under the control of a suitable promoter (CMV-promoter) and a suitable resistance marker (neomycin). Using standard techniques the expression plasmid is transfected into G-402 cells and these cells are then selected for expressing the given resistance markers. Individual cell-clones are then selected and assessed for displaying the desired enzymatic activity using 11-Deoxycorticosterone (Cyp11B2) or 11-Deoxycortisol (Cyp11B1) as a substrate. G-402 cells expressing CYP11 constructs were established as described above and maintained in McCoy's 5a Medium Modified, ATCC Catalog No. 30-2007 containing 10% FCS and 400 μg/ml G418 (Geneticin) at 37° C. under an atmosphere of 5% CO2/95% air. Cellular enzyme assays were performed in DMEM/F12 medium containing 2.5% charcoal treated FCS and appropriate concentration of substrate (0.3-10 μM 11-Deoxycorticosterone, 11-Deoxycortisol or Corticosterone). For assaying enzymatic activity, cells were plated onto 96 well plates and incubated for 16 h. An aliquot of the supernatant is then transferred and analyzed for the concentration of the expected product (Aldosterone for CYP11B2; Cortisol for CYP11B1). The concentrations of these steroids can be determined using HTRF assays from CisBio analyzing either Aldosterone or Cortisol.
Measurement: EC50 = 42551 nM (pChEMBL 4.369999885559082)
Descriptors: MW 381.45, ALogP 3.7, HBA 3, HBD 1, PSA 62.3, QED 0.88
Compound (SMILES): O=[N+]([O-])c1cccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5cccc([N+](=O)[O-])c5)ccc4o3)cc2)c1
InChIKey: HZTHWLZNEZZGCI-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 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 595.57, ALogP 4.91, HBA 10, HBD 2, PSA 204.65, QED 0.17
Compound (SMILES): CCCSc1nc2c(c(=O)n1-c1ccccc1)SCC2
InChIKey: YHNDCCKFNWDQGW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 304.44, ALogP 3.38, HBA 5, HBD 0, PSA 34.89, QED 0.64
Compound (SMILES): Cn1cc2c(nc(NCCCCCNC(=S)Nc3ccc(-c4c5ccc(=O)cc-5oc5cc(O)ccc45)c(C(=O)O)c3)n3nc(-c4ccco4)nc23)n1
InChIKey: GJQZTOMIXVZSNR-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]-AB-MECA from human adenosine A3 receptor expressed in CHO cells by radioligand competition analysis
Measurement: Ki = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 729.78, ALogP 6.12, HBA 13, HBD 5, PSA 197.87, QED 0.06
Compound (SMILES): COc1cc(OC)cc(N(Cc2ncc[nH]2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GWCJUEKQORIUTJ-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 absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 441.5, ALogP 4.11, HBA 8, HBD 1, PSA 93.98, QED 0.41
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCOC[C@H]2CO1
InChIKey: CMTRUERFSJKMJQ-KBPBESRZSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 553.82, ALogP 4.42, HBA 8, HBD 1, PSA 77.97, QED 0.45
Compound (SMILES): N#Cc1c(N)nc(N)nc1N[C@H](c1nc2c(F)ccc(Cl)c2c(=O)n1-c1cccnc1)C1CC1
InChIKey: XDSXYMOZKDUASY-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human full length PI3K p110gamma using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 477.89, ALogP 2.96, HBA 10, HBD 3, PSA 161.42, QED 0.39
Compound (SMILES): CCc1ccc(OCCNc2nc(Nc3cc(C)[nH]n3)cc(C)c2C#N)cn1
InChIKey: NKWGBOOLJXYPQR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 377.45, ALogP 3.49, HBA 7, HBD 3, PSA 111.54, QED 0.52
Compound (SMILES): Cc1c(Nc2c(CO)nc3c(N)cc(N4CCOC(CO)C4)nn23)cccc1C(F)(F)F
InChIKey: KHWGXDFXYVESQN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to human PI3Kdelta (108 to 1044 residues) expressed in mammalian expression system by KINOMEscan assay
Measurement: Kd = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 452.44, ALogP 2.07, HBA 9, HBD 4, PSA 121.17, QED 0.46
Compound (SMILES): CO[C@H]1CC[C@]2(CC1)Cc1ccc(-c3ccc(F)c(C#N)c3)cc1C21N=C(C)C(N)=N1
InChIKey: GJVWSAKHBXGRHV-QXONTCKQSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: sAPPbeta Release Assay: SH-SY5Y cells were cultured in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids and cryopreserved and stored at −140° C. at a concentration of 7.5-9.5×106 cells per vial. Thaw cells and seed at a conc. of around 10000 cells/well in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids to a 384-well tissue culture treated plate, 100 μL cell susp/well. The cell plates were then incubated for 7-24 h at 37° C., 5% CO2. The cell medium was removed, followed by addition of 30 μL compound diluted in DMEM/F-12 with Glutamax, 10% FCS, 1% non-essential amino acids and 1% PeSt to a final conc. of 1% DMSO. The compounds were incubated with the cells for 17 h (overnight) at 37° C., 5% CO2. Meso Scale Discovery (MSD) plates were used for the detection of sAPPβ release. MSD sAPPβ plates were blocked in 1% BSA in Tris wash buffer (40 μL/well) for 1 h on shake at r.t. and washed 1 time in Tris wash buffer (40 μL/well). 20 μL of medium was transferred to the pre-blocked and washed MSD sAPPβ microplates, and the cell plates were further used in an ATP assay to measure cytotoxicity. The MSD plates were incubated with shaking at r.t. for 2 h and the media discarded. 10 μL detection antibody was added (1 nM) per well followed by incubation with shaking at r.t. for 2 h and then discarded. 40 μL Read Buffer was added per well and the plates were read in a SECTOR Imager.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 416.5, ALogP 4.48, HBA 5, HBD 1, PSA 83.76, QED 0.78
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(F)cc(F)c3)CC2)C1
InChIKey: RLGJETWHGLSOSB-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 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 502.53, ALogP 3.33, HBA 7, HBD 1, PSA 106.73, QED 0.45
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)OCc3cc(F)cc(F)c3)CC2)C1
InChIKey: NGMZDEADJNNQBR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
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 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 532.56, ALogP 3.83, HBA 8, HBD 1, PSA 115.96, QED 0.4
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(F)cc3Cl)CC2)C1
InChIKey: SLQZHPOAPCUKGW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 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 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 533.01, ALogP 4.84, HBA 6, HBD 2, PSA 105.87, QED 0.38
Compound (SMILES): N[C@H](C(=O)O)C(NS(=O)(=O)c1ccc2ccccc2c1)C(=O)O
InChIKey: PSIIUSMBTVCZCJ-PXYINDEMSA-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 = 8912.51 nM (pChEMBL 5.050000190734863)
Descriptors: MW 338.34, ALogP -0.02, HBA 5, HBD 4, PSA 146.79, QED 0.58
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(C(=O)NCC)nc4)cc23)c1F
InChIKey: AACPHNFEDMXRPQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 527.55, ALogP 4.04, HBA 6, HBD 3, PSA 133.91, QED 0.28
Compound (SMILES): CNC(=O)c1cc(OC2CCC(NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)CC2)ccn1
InChIKey: VZOUKWZMPPMODY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: ADP-Glo Kinase Assay: Inhibitor Concentration at 50% enzyme inhibition (IC50) values were calculated by quantifying the end-point ADP production from each kinase reaction using the ADP-Glo Kinase Assay (Promega, Madison, Wis.) as described by the manufacturer. Reactions were performed in Tris buffer (50 mM pH 7.5, RT) containing 20 mM MgCl2 and 0.1% Bovine Serum Albumin. Each assay was performed in 60 uL of the solution in 10x75 mm borosilicate glass test tubes and allowed to continuously shake during the duration of the assay. The total ADP generated was quantified by transferring 25 uL (2x) of each assay to a 96-well luminescence assay plate, followed by the addition of 25 uL of ADP-Glo Reagent (45 min incubation) to remove any remaining ATP. For luminescence readings, 50 uL of Kinase Detection Reagent (45 min incubation) was added to convert the ADP generated from the kinase reaction to ATP, and luminescent intensity was measured using a luciferase/luciferin reaction.
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 470.88, ALogP 4.63, HBA 4, HBD 3, PSA 92.35, QED 0.59
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3ccnc(OC)c3)nc3cc(C)ccn23)c(C#Cc2ccc3c(C)nccc3c2)n1
InChIKey: DOCWUWPIDUHYPB-QHCPKHFHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 581.68, ALogP 5.58, HBA 8, HBD 2, PSA 106.33, QED 0.25
Compound (SMILES): N#Cc1c[nH]c2nccc(-c3ccsc3)c12
InChIKey: BHEBICBPOTVZFO-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 = 851 nM (pChEMBL 6.070000171661377)
Descriptors: MW 225.28, ALogP 3.16, HBA 3, HBD 1, PSA 52.47, QED 0.69
Compound (SMILES): Cc1cccc2ccc(N3CC[C@H](C(=O)N[C@H]4CCO[C@H](CO)C4)C(C)(C)C3)nc12
InChIKey: OLJFTJILJDDJGV-SLFFLAALSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Canis lupus familiaris
UniProt: A0SYQ0
Assay: Inhibition of mPGES-1 in dog whole blood
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 411.55, ALogP 3.05, HBA 5, HBD 2, PSA 74.69, QED 0.81
Compound (SMILES): COc1cc(F)cc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: BMTRLYMQWMETEI-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 absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 389.43, ALogP 4.72, HBA 5, HBD 1, PSA 66.93, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC5CCOCC5)c4)nc3c2)c1
InChIKey: GYKUJANUHZAPRA-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 absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.62, ALogP 5.49, HBA 8, HBD 0, PSA 74.53, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CC1
InChIKey: SDPXNCYWHLAZJC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 390.27, ALogP 5.48, HBA 5, HBD 1, PSA 56.27, QED 0.6
Compound (SMILES): COC(=O)CCC/C=C\C[C@H]1C(=O)C(C)(C)[C@@H](O)[C@@H]1/C=C/C(O)CCc1ccccc1
InChIKey: ZELKHLBDQHQEJW-NRBAOQCDSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding: HEK-293 cells stably expressing the human or feline FP receptor, or EP1, EP2, EP3, or EP4 receptors were washed with TME buffer, scraped from the bottom of the flasks, and homogenized for 30 sec using a Brinkman PT 10/35 polytron. TME buffer was added to achieve a final 40 ml volume in the centrifuge tubes (the composition of TME is 100 mM TRIS base, 20 mM MgCl2, 2M EDTA; 10 N HCl is added to achieve a pH of 7.4).The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4 C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2 (5 nM) were performed in a 100 ul volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell.
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 428.57, ALogP 4.03, HBA 5, HBD 2, PSA 83.83, QED 0.32
Compound (SMILES): COc1cccc(N(C(=O)OC[C@H]2CC[C@H](COCC(=O)O)CC2)c2ccccc2)c1
InChIKey: RPNYUFBHLRPFJE-WGSAOQKQSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
Assay: Agonist activity at IP receptor in human primary platelets assessed as inhibition of ADP-induced platelet aggregation
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 427.5, ALogP 4.88, HBA 5, HBD 1, PSA 85.3, QED 0.61
Compound (SMILES): COc1ccn2c(-c3ccnc(Nc4cccc(OCCN(C)C)c4)n3)c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc2c1
InChIKey: JHAJPTOYCXHOLN-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 665.7, ALogP 6.69, HBA 10, HBD 2, PSA 115.14, QED 0.15
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2c(F)cccc2F)c1F)c1c[nH]c2nccc(Cl)c12
InChIKey: LZXVWIKLBIDGKX-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.83, ALogP 4.8, HBA 4, HBD 2, PSA 91.92, QED 0.31
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2CO1
InChIKey: FSJDACURTSWGHC-HOTGVXAUSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 475.38, ALogP 4.93, HBA 7, HBD 1, PSA 68.74, QED 0.54
Compound (SMILES): COc1cc(N(CCCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)cc(OC)c1C(O)C(F)(F)F
InChIKey: DWSQRXVYJVMLAJ-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 absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 516.52, ALogP 4.13, HBA 9, HBD 2, PSA 111.55, QED 0.34
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(Cl)c2c(=O)n1-c1cccnc1
InChIKey: XJFBDHGCAVAKJA-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human full length PI3K p110gamma using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 433.86, ALogP 2.43, HBA 10, HBD 3, PSA 161.42, QED 0.44
Compound (SMILES): CCc1cc(O)ccc1-c1ccc2c(-c3nc4ccccc4[nH]3)n[nH]c2c1
InChIKey: CSLGOZXFBHTYAA-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human CDK2 expressed in baculovirus infected Sf9 insect cells/full length recombinant truncated cyclin A expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by [32P]ATP based scintillation counting analysis
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 354.41, ALogP 5.04, HBA 3, HBD 3, PSA 77.59, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)cc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IJQYMGBALOJSDL-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 absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 485.98, ALogP 6.04, HBA 7, HBD 0, PSA 65.3, QED 0.28
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3cccc(C#N)c3)CC2)C1
InChIKey: FYAIMVZLZTXMKX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 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 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 477.58, ALogP 3.28, HBA 8, HBD 1, PSA 113.45, QED 0.45
Compound (SMILES): Cc1c(-c2c(Cl)cc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: IRBVGTPPFBYDKX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required for inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations.
Measurement: IC50 = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 587.46, ALogP 5.69, HBA 6, HBD 3, PSA 122.59, QED 0.25
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)cc(Cl)n1
InChIKey: JPXPFBBAKOKSRT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
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 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 532.01, ALogP 3.11, HBA 9, HBD 1, PSA 128.85, QED 0.38
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cccc(C(F)(F)F)c3F)CC2)C1
InChIKey: KHHTXXKIWBHJGR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 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 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 552.54, ALogP 4.21, HBA 7, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc2ccc(Cl)cc12
InChIKey: QQGZOWNAHJAXCG-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
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 516.84, ALogP 8.14, HBA 6, HBD 1, PSA 56.27, QED 0.25