lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@@H]1C[C@](O)(C(F)(F)F)[C@@H](Nc2cccc3[nH]c(=O)ccc23)c2cc(F)c(F)c(O)c21
InChIKey: VZPLUSXTJULLCS-SYQZRHMFSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Agonist activity at glucocorticoid receptor in human ChaGoK1 cells assessed as inhibition of AP1-mediated transcriptional activity by measuring reduction in PMA-stimulated TRE-LacZ activity after 24 hrs in presence of MUG by fluorometric assay
Measurement: IC50 = 1.15 nM (pChEMBL 8.9399995803833)
Descriptors: MW 454.39, ALogP 4.86, HBA 4, HBD 4, PSA 85.35, QED 0.43
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2CO1
InChIKey: VEZBREXQDQRJTD-KBPBESRZSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
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 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 537.82, ALogP 5.18, HBA 7, HBD 1, PSA 68.74, QED 0.43
Compound (SMILES): COc1cc(O)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HHRGGSVSAUUCLO-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 = 3.89 nM (pChEMBL 8.40999984741211)
Descriptors: MW 391.43, ALogP 2.87, HBA 8, HBD 2, PSA 96.53, QED 0.52
Compound (SMILES): CCOc1cc(F)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QCYDLOHINRAHID-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 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 407.45, ALogP 3.7, HBA 7, HBD 1, PSA 76.3, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MZLXXVIDRYUZIM-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 = 5.129 nM (pChEMBL 8.289999961853027)
Descriptors: MW 515.66, ALogP 4.21, HBA 9, HBD 0, PSA 71.78, QED 0.33
Compound (SMILES): COCCNC(=O)C(C)(C)n1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NGLRSTVZLVHSJO-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 = 8.318 nM (pChEMBL 8.079999923706055)
Descriptors: MW 544.66, ALogP 4.56, HBA 9, HBD 1, PSA 103.63, QED 0.26
Compound (SMILES): Cc1ncc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cnc(OC2CCOCC2)c(N2CCOCC2)c1
InChIKey: FYNMINFUAIDIFL-UHFFFAOYSA-N
Target: BRAF/CRAF (PROTEIN COMPLEX), Homo sapiens
UniProt: P04049
Assay: Stimulation of BRAF-CRAF dimerization in human HCT116 cells by luciferase complementation assay
Measurement: EC50 = 796 nM (pChEMBL 6.099999904632568)
Descriptors: MW 542.56, ALogP 5.12, HBA 7, HBD 1, PSA 85.81, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCCC5)c4)nc3c2)c1.Cl
InChIKey: PAWXGXHMRSTMFA-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 = 5.129 nM (pChEMBL 8.289999961853027)
Descriptors: MW 498.63, ALogP 5.15, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): CC(C(=O)NC1COc2ncccc21)c1cccc(C(F)(F)F)c1Cl
InChIKey: CGZWZKJDTFHJQE-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: In Vitro Assay: Cell line generation was performed in general according to established molecular cloning protocols. Specifically, RNA was extracted from human whole blood using the Qiagen RNeasy kit (Qiagen, CH) according to the manufacturer's instructions. Subsequently cDNA was made (Superscript II, Invitrogen AG, CH) and the human P2X7 gene (genbank ref. BC011913) was amplified with the following primers: ATCGCGGCCGCTCAGTAAGGACTCTTGAAGCCACT and CGCCGCTAGCACCACCATGCCGGCCTGCTGCAGCTGCA. The amplified sequence was subsequently ligated into a pcDNA3.1 (+) NotI, NheI digested plasmid. Human embryonic kidney (HEK) cells (ATCC CRL-1573, Manassas, Va., USA) were transfected with the pcDNA3.1 (+). hP2X7 plasmid using lipofectamine 2000 (Invitrogen AG, CH) according to the manufacturer's instructions. Following a 24 h exposure to DNA, cells were trypsinized and re-seeded at low density in the presence of 250 ug Geneticin. Geneticin resistant cells were then selected during two consecutive rounds of cloning by serial limiting dilution with visual inspection.
Measurement: IC50 = 308 nM (pChEMBL 6.510000228881836)
Descriptors: MW 370.76, ALogP 4.11, HBA 3, HBD 1, PSA 51.22, QED 0.88
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCN(C(N)=O)CC1
InChIKey: VQODXNCHOGDXSX-YKSBVNFPSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in microsomes using ER as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 522.64, ALogP 4.45, HBA 6, HBD 1, PSA 80.28, QED 0.43
Compound (SMILES): COC(=O)c1cccnc1C#CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: JBMDPQHNWRVKTP-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 = 23.44 nM (pChEMBL 7.630000114440918)
Descriptors: MW 534.58, ALogP 4.42, HBA 10, HBD 0, PSA 104.49, QED 0.22
Compound (SMILES): CC1CCN(C(=O)OC(C)(C)C)CC1c1nnn2cnc3[nH]ccc3c12
InChIKey: IVFATVRABARRFI-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 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 356.43, ALogP 2.97, HBA 6, HBD 1, PSA 88.41, QED 0.72
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ARDLUUQELBPNNT-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 = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 472.55, ALogP 3.71, HBA 8, HBD 1, PSA 94.4, QED 0.4
Compound (SMILES): COCc1c(-c2cc3cc(C)cc(OC)c3s2)c2c(N)ncnn2c1CN1CCNC(=O)C1
InChIKey: HNLRRJSKGXOYNO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human recombinant FGFR4 in the presence of ATP at 0.8 uM measured after 1 hr by fluorescence based assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 466.57, ALogP 2.59, HBA 9, HBD 2, PSA 107.01, QED 0.45
Compound (SMILES): Cc1nc(C2CCCCC2)c2c3cc[nH]c3ncn12
InChIKey: VEBMETUDINBSIP-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.
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 254.34, ALogP 3.57, HBA 3, HBD 1, PSA 45.98, QED 0.72
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(-c2ccc(Cl)cc2)n1
InChIKey: KIHIMMDNUNDKTJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
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 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 543.86, ALogP 8.04, HBA 7, HBD 1, PSA 69.16, QED 0.22
Compound (SMILES): Cl.c1ccc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)cc1
InChIKey: XRTFMLXFXJOUEC-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 = 851.14 nM (pChEMBL 6.070000171661377)
Descriptors: MW 341.42, ALogP 4.57, HBA 4, HBD 1, PSA 57.7, QED 0.58
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(F)cc3)C2)n1C
InChIKey: XRDPJIJIWYVCKW-PGRDOPGGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in microsomes using 7BQ as substrate after 10 mins by P450 cypex assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 427.55, ALogP 4.28, HBA 7, HBD 0, PSA 59.98, QED 0.41
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)F)cc3)c(N)c2c1C
InChIKey: KNZAIFIZJGFOCI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-N-Methylscopolamine from human M1 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.47, ALogP 2.82, HBA 7, HBD 2, PSA 115.04, QED 0.65
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XJOQXSSQHKPXSP-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 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 415.5, ALogP 4.6, HBA 7, HBD 0, PSA 65.3, QED 0.44
Compound (SMILES): CCCOc1ccc(CCc2nc3cc(-c4c(C)noc4C)ccc3n2CCN2CCOCC2)cc1
InChIKey: CGWBJJZOKGZCSJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to recombinant BRD4 bromodomain1 (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 488.63, ALogP 5.21, HBA 7, HBD 0, PSA 65.55, QED 0.31
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(F)nc4)cc23)c1F
InChIKey: UBJUBKFKARGYJS-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.46, ALogP 4.42, HBA 5, HBD 2, PSA 104.81, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccnc(N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DBFMFHYDGXJVLJ-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 = 5.495 nM (pChEMBL 8.260000228881836)
Descriptors: MW 492.54, ALogP 3.61, HBA 10, HBD 1, PSA 117.1, QED 0.35
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: WDACLZKYOGTKNW-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 = 2.455 nM (pChEMBL 8.609999656677246)
Descriptors: MW 418.5, ALogP 3.87, HBA 7, HBD 3, PSA 99.19, QED 0.4
Compound (SMILES): Cc1cccc(-c2cc(N)nc3[nH]cc(C#N)c23)c1
InChIKey: KWTGXMXCSXFSJX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant phosphorylation at ser935 transfected in HEK293 cells after 48 hrs by in-cell Western assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 248.29, ALogP 2.99, HBA 3, HBD 2, PSA 78.49, QED 0.69
Compound (SMILES): CNCCN1CCC(OCc2ccccc2)CC1
InChIKey: HBOJWAYLSJLULG-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Inhibition of PRMT3 (unknown origin) assessed as inhibition of methylation activity measured after 3 hrs using [3H]-SAM by scintillation proximity assay
Measurement: IC50 > 22000 nM (pChEMBL 4.6579999923706055)
Descriptors: MW 248.37, ALogP 1.89, HBA 3, HBD 1, PSA 24.5, QED 0.83
Compound (SMILES): COc1nc(N(CC(C)(C)F)c2cc(Cl)c(F)cc2F)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: RVMWIVNHZMXEHS-UWVGGRQHSA-N
Target: Leukotriene C4 synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16873
Assay: Inhibition of LTC4S in human PBMC cells assessed as inhibition of calcium ionophore A23187 stimulated LTC4 release preincubated for 15 mins followed by calcium ionophore stimulation and measured after 2 hrs by FRET analysis
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 457.84, ALogP 4.21, HBA 6, HBD 1, PSA 92.62, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(Cc2csc(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IIGRWRUGUUITMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 472.57, ALogP 5.15, HBA 9, HBD 0, PSA 78.19, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC[C@H](C#N)C2)c2ccc3ncc(-c4cnn(CC5CCOCC5)c4)nc3c2)c1
InChIKey: FNJXQSFBTXMNDB-XMMPIXPASA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (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 = 38.02 nM (pChEMBL 7.420000076293945)
Descriptors: MW 567.69, ALogP 4.92, HBA 10, HBD 0, PSA 101.56, QED 0.26
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1cc(Br)cc(Br)c1
InChIKey: YETQQFMHUDZVIA-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
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 584.1, ALogP 7.79, HBA 5, HBD 1, PSA 56.27, QED 0.25
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2cc(F)cc(CS(C)(=N)=O)c2)ncc1F
InChIKey: NSJOYQIOHVHMCZ-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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 422.43, ALogP 4.49, HBA 6, HBD 2, PSA 87.96, QED 0.61
Compound (SMILES): Cc1cc(Nc2nc([C@H](O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
InChIKey: DCRWIATZWHLIPN-QGZVFWFLSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: CYP450 Inhibition Assay: The ability of the R and S enantiomers of (4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol to inhibit the common drug metabolizing isoforms of cytochrome P450 (CYP) was evaluated against the following isoforms: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The compounds were incubated in duplicate with eight test compound concentrations (final DMSO concentration of 0.20%) with human liver microsomes (0.25 or 0.50 mg/mL) and NADPH (1 mM) in the presence of CYP isoform specific probe substrates (phenacetin, bupropion, taxol, diclofenac, mephenyloin, dextromethorphan, testosterone) at the Km for 10-20 minutes at 37° C. Selective CYP isoform inhibitors (furafulline, ticlopidine, quercetin, sulfaphenazole, ticlopidine, quinidine, ketoconazole) were screened alongside the test compounds as positive controls.
Measurement: IC50 = 26900 nM (pChEMBL 4.570000171661377)
Descriptors: MW 349.37, ALogP 3.63, HBA 5, HBD 3, PSA 86.72, QED 0.52
Compound (SMILES): COC(=O)Nc1ccc(S(=O)(=O)C(C)C)c([C@H]2CCCN2C(=O)[C@H](Nc2cc3c(cc2F)CNC3=O)c2ccc(OC)c(OC)c2)c1
InChIKey: BPIJQVAKJCDFPD-PDDLMNHVSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of human urokinase
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 668.74, ALogP 4.96, HBA 9, HBD 3, PSA 152.37, QED 0.27
Compound (SMILES): COc1cc(O)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HHRGGSVSAUUCLO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 0.8318 nM (pChEMBL 9.079999923706055)
Descriptors: MW 391.43, ALogP 2.87, HBA 8, HBD 2, PSA 96.53, QED 0.52
Compound (SMILES): CCOc1cc(F)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QCYDLOHINRAHID-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.898 nM (pChEMBL 8.3100004196167)
Descriptors: MW 407.45, ALogP 3.7, HBA 7, HBD 1, PSA 76.3, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MZLXXVIDRYUZIM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 515.66, ALogP 4.21, HBA 9, HBD 0, PSA 71.78, QED 0.33
Compound (SMILES): COCCNC(=O)C(C)(C)n1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NGLRSTVZLVHSJO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.57 nM (pChEMBL 8.59000015258789)
Descriptors: MW 544.66, ALogP 4.56, HBA 9, HBD 1, PSA 103.63, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCCC5)c4)nc3c2)c1.Cl
InChIKey: PAWXGXHMRSTMFA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.236 nM (pChEMBL 8.489999771118164)
Descriptors: MW 498.63, ALogP 5.15, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): CC(C(=O)NC1COc2ncccc21)c1cccc(C(F)(F)F)c1Cl
InChIKey: CGZWZKJDTFHJQE-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: In Vitro Assay: Cell line generation was performed in general according to established molecular cloning protocols. Specifically, RNA was extracted from human whole blood using the Qiagen RNeasy kit (Qiagen, CH) according to the manufacturer's instructions. Subsequently cDNA was made (Superscript II, Invitrogen AG, CH) and the human P2X7 gene (genbank ref. BC011913) was amplified with the following primers: ATCGCGGCCGCTCAGTAAGGACTCTTGAAGCCACT and CGCCGCTAGCACCACCATGCCGGCCTGCTGCAGCTGCA. The amplified sequence was subsequently ligated into a pcDNA3.1 (+) NotI, NheI digested plasmid. Human embryonic kidney (HEK) cells (ATCC CRL-1573, Manassas, Va., USA) were transfected with the pcDNA3.1 (+). hP2X7 plasmid using lipofectamine 2000 (Invitrogen AG, CH) according to the manufacturer's instructions. Following a 24 h exposure to DNA, cells were trypsinized and re-seeded at low density in the presence of 250 ug Geneticin. Geneticin resistant cells were then selected during two consecutive rounds of cloning by serial limiting dilution with visual inspection.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 370.76, ALogP 4.11, HBA 3, HBD 1, PSA 51.22, QED 0.88
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCN(C(N)=O)CC1
InChIKey: VQODXNCHOGDXSX-YKSBVNFPSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 expressed in microsomes using FCA as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 522.64, ALogP 4.45, HBA 6, HBD 1, PSA 80.28, QED 0.43
Compound (SMILES): COC(=O)c1cccnc1C#CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: JBMDPQHNWRVKTP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 534.58, ALogP 4.42, HBA 10, HBD 0, PSA 104.49, QED 0.22
Compound (SMILES): CC1CCN(C(=O)OC(C)(C)C)CC1c1nnn2cnc3[nH]ccc3c12
InChIKey: IVFATVRABARRFI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 560 nM (pChEMBL 6.25)
Descriptors: MW 356.43, ALogP 2.97, HBA 6, HBD 1, PSA 88.41, QED 0.72
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ARDLUUQELBPNNT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 472.55, ALogP 3.71, HBA 8, HBD 1, PSA 94.4, QED 0.4
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(-c2ccc(Cl)cc2)n1
InChIKey: KIHIMMDNUNDKTJ-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
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 543.86, ALogP 8.04, HBA 7, HBD 1, PSA 69.16, QED 0.22
Compound (SMILES): Cl.c1ccc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)cc1
InChIKey: XRTFMLXFXJOUEC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 776.25 nM (pChEMBL 6.110000133514404)
Descriptors: MW 341.42, ALogP 4.57, HBA 4, HBD 1, PSA 57.7, QED 0.58
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(F)cc3)C2)n1C
InChIKey: XRDPJIJIWYVCKW-PGRDOPGGSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor expressed in CHO cell membranes after 90 mins in presence of quinelorane by [35S]-GTPgammaS binding assay
Measurement: Ki = 0.5248 nM (pChEMBL 9.279999732971191)
Descriptors: MW 427.55, ALogP 4.28, HBA 7, HBD 0, PSA 59.98, QED 0.41
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)F)cc3)c(N)c2c1C
InChIKey: KNZAIFIZJGFOCI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-N-Methylscopolamine from human M2 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.47, ALogP 2.82, HBA 7, HBD 2, PSA 115.04, QED 0.65
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XJOQXSSQHKPXSP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 415.5, ALogP 4.6, HBA 7, HBD 0, PSA 65.3, QED 0.44
Compound (SMILES): CCCOc1ccc(CCc2nc3cc(-c4c(C)noc4C)ccc3n2CCN2CCOCC2)cc1
InChIKey: CGWBJJZOKGZCSJ-UHFFFAOYSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Selectivity interaction (BROMOscan (DiscoverX)) EUB0002298a EP300
Measurement: IC50 = 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 488.63, ALogP 5.21, HBA 7, HBD 0, PSA 65.55, QED 0.31
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(F)nc4)cc23)c1F
InChIKey: UBJUBKFKARGYJS-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.46, ALogP 4.42, HBA 5, HBD 2, PSA 104.81, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccnc(N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DBFMFHYDGXJVLJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 492.54, ALogP 3.61, HBA 10, HBD 1, PSA 117.1, QED 0.35
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: WDACLZKYOGTKNW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.202 nM (pChEMBL 8.920000076293945)
Descriptors: MW 418.5, ALogP 3.87, HBA 7, HBD 3, PSA 99.19, QED 0.4
Compound (SMILES): Cc1cccc(-c2cc(N)nc3[nH]cc(C#N)c23)c1
InChIKey: KWTGXMXCSXFSJX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant phosphorylation at ser935 transfected in HEK293 cells after 48 hrs by in-cell Western assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 248.29, ALogP 2.99, HBA 3, HBD 2, PSA 78.49, QED 0.69
Compound (SMILES): CNCCN1CCC(OCc2ccccc2)CC1
InChIKey: HBOJWAYLSJLULG-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Inhibition of PRMT1 (unknown origin) assessed as inhibition of methylation activity measured after 3 hrs using [3H]-SAM by scintillation proximity assay
Measurement: IC50 > 13000 nM (pChEMBL 4.886000156402588)
Descriptors: MW 248.37, ALogP 1.89, HBA 3, HBD 1, PSA 24.5, QED 0.83
Compound (SMILES): COc1nc(N(CC(C)(C)F)c2cc(Cl)c(F)cc2F)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: RVMWIVNHZMXEHS-UWVGGRQHSA-N
Target: Leukotriene C4 synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16873
Assay: Inhibition of LTC4S in human whole blood assessed as inhibition of calcium ionophore A23187 stimulated LTC4 release preincubated with compound for 4 hrs followed by calcium ionophore stimulation and measured after 15 mins by competitive immunoassays EIA analysis
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 457.84, ALogP 4.21, HBA 6, HBD 1, PSA 92.62, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(Cc2csc(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IIGRWRUGUUITMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 472.57, ALogP 5.15, HBA 9, HBD 0, PSA 78.19, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC[C@H](C#N)C2)c2ccc3ncc(-c4cnn(CC5CCOCC5)c4)nc3c2)c1
InChIKey: FNJXQSFBTXMNDB-XMMPIXPASA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (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 567.69, ALogP 4.92, HBA 10, HBD 0, PSA 101.56, QED 0.26
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2cc(F)cc(CS(C)(=N)=O)c2)ncc1F
InChIKey: NSJOYQIOHVHMCZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Carbonic Anhydrase Assay: The principle of the assay is based on the hydrolysis of 4-nitrophenyl acetate by carbonic anhydrases (Pocker & Stone, Biochemistry, 1967, 6, 668), with subsequent photometric determination of the dye product 4-nitrophenolate at 400 nm by means of a 96-channel spectral photometer. 2 uL of the test compounds, dissolved in DMSO (100-fold final concentration), in a concentration range of 0.03-10 umol/L (final), was pipetted as quadruplicates into the wells of a 96-hole microtiter plate. Wells that contained the solvent without test compounds were used as reference values (1. Wells without carbonic anhydrase for correction of the non-enzymatic hydrolysis of the substrate, and 2. Wells with carbonic anhydrase for determining the activity of the non-inhibited enzyme). 188 uL of assay buffer (10 mmol/L of Tris/HCl, pH 7.4, 80 mmol/L of NaCl), with or without 3 units/well of carbonic anhydrase-1 [=human carbonic anhydrase-1.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.43, ALogP 4.49, HBA 6, HBD 2, PSA 87.96, QED 0.61
Compound (SMILES): Cc1cc(Nc2nc([C@H](O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
InChIKey: DCRWIATZWHLIPN-QGZVFWFLSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: CYP450 Inhibition Assay: The ability of the R and S enantiomers of (4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol to inhibit the common drug metabolizing isoforms of cytochrome P450 (CYP) was evaluated against the following isoforms: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The compounds were incubated in duplicate with eight test compound concentrations (final DMSO concentration of 0.20%) with human liver microsomes (0.25 or 0.50 mg/mL) and NADPH (1 mM) in the presence of CYP isoform specific probe substrates (phenacetin, bupropion, taxol, diclofenac, mephenyloin, dextromethorphan, testosterone) at the Km for 10-20 minutes at 37° C. Selective CYP isoform inhibitors (furafulline, ticlopidine, quercetin, sulfaphenazole, ticlopidine, quinidine, ketoconazole) were screened alongside the test compounds as positive controls.
Measurement: IC50 = 15200 nM (pChEMBL 4.820000171661377)
Descriptors: MW 349.37, ALogP 3.63, HBA 5, HBD 3, PSA 86.72, QED 0.52
Compound (SMILES): COC(=O)Nc1ccc(S(=O)(=O)C(C)C)c([C@H]2CCCN2C(=O)[C@H](Nc2cc3c(cc2F)CNC3=O)c2ccc(OC)c(OC)c2)c1
InChIKey: BPIJQVAKJCDFPD-PDDLMNHVSA-N
Target: Vitamin K-dependent protein C (SINGLE PROTEIN), Homo sapiens
UniProt: P04070
Assay: Inhibition of human activated protein C
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 668.74, ALogP 4.96, HBA 9, HBD 3, PSA 152.37, QED 0.27
Compound (SMILES): COc1cc(O)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HHRGGSVSAUUCLO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 391.43, ALogP 2.87, HBA 8, HBD 2, PSA 96.53, QED 0.52
Compound (SMILES): CCOc1cc(F)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QCYDLOHINRAHID-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 72.44 nM (pChEMBL 7.139999866485596)
Descriptors: MW 407.45, ALogP 3.7, HBA 7, HBD 1, PSA 76.3, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MZLXXVIDRYUZIM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 515.66, ALogP 4.21, HBA 9, HBD 0, PSA 71.78, QED 0.33
Compound (SMILES): COCCNC(=O)C(C)(C)n1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NGLRSTVZLVHSJO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 42.66 nM (pChEMBL 7.369999885559082)
Descriptors: MW 544.66, ALogP 4.56, HBA 9, HBD 1, PSA 103.63, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCCC5)c4)nc3c2)c1.Cl
InChIKey: PAWXGXHMRSTMFA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 498.63, ALogP 5.15, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): CC(C(=O)NC1COc2ncccc21)c1cccc(C(F)(F)F)c1Cl
InChIKey: CGZWZKJDTFHJQE-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: In Vitro Assay: Cell line generation was performed in general according to established molecular cloning protocols. Specifically, RNA was extracted from human whole blood using the Qiagen RNeasy kit (Qiagen, CH) according to the manufacturer's instructions. Subsequently cDNA was made (Superscript II, Invitrogen AG, CH) and the human P2X7 gene (genbank ref. BC011913) was amplified with the following primers: ATCGCGGCCGCTCAGTAAGGACTCTTGAAGCCACT and CGCCGCTAGCACCACCATGCCGGCCTGCTGCAGCTGCA. The amplified sequence was subsequently ligated into a pcDNA3.1 (+) NotI, NheI digested plasmid. Human embryonic kidney (HEK) cells (ATCC CRL-1573, Manassas, Va., USA) were transfected with the pcDNA3.1 (+). hP2X7 plasmid using lipofectamine 2000 (Invitrogen AG, CH) according to the manufacturer's instructions. Following a 24 h exposure to DNA, cells were trypsinized and re-seeded at low density in the presence of 250 ug Geneticin. Geneticin resistant cells were then selected during two consecutive rounds of cloning by serial limiting dilution with visual inspection.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 370.76, ALogP 4.11, HBA 3, HBD 1, PSA 51.22, QED 0.88
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCN(C(N)=O)CC1
InChIKey: VQODXNCHOGDXSX-YKSBVNFPSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in microsomes using BMC as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 522.64, ALogP 4.45, HBA 6, HBD 1, PSA 80.28, QED 0.43
Compound (SMILES): COC(=O)c1cccnc1C#CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: JBMDPQHNWRVKTP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 46.77 nM (pChEMBL 7.329999923706055)
Descriptors: MW 534.58, ALogP 4.42, HBA 10, HBD 0, PSA 104.49, QED 0.22
Compound (SMILES): CC1CCN(C(=O)OC(C)(C)C)CC1c1nnn2cnc3[nH]ccc3c12
InChIKey: IVFATVRABARRFI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
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 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 356.43, ALogP 2.97, HBA 6, HBD 1, PSA 88.41, QED 0.72
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ARDLUUQELBPNNT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 472.55, ALogP 3.71, HBA 8, HBD 1, PSA 94.4, QED 0.4
Compound (SMILES): Cl.c1ccc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)cc1
InChIKey: XRTFMLXFXJOUEC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 341.42, ALogP 4.57, HBA 4, HBD 1, PSA 57.7, QED 0.58
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(F)cc3)C2)n1C
InChIKey: XRDPJIJIWYVCKW-PGRDOPGGSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human dopamine D2L receptor expressed in CHO cells coexpressing Galpha16 assessed as inhibition of dopamine-induced Ca2+ stimulation pre-incubated for 10 mins followed by dopamine challenge by Fluo-4AM based fluorometric analysis
Measurement: Ki = 57.54 nM (pChEMBL 7.239999771118164)
Descriptors: MW 427.55, ALogP 4.28, HBA 7, HBD 0, PSA 59.98, QED 0.41
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)F)cc3)c(N)c2c1C
InChIKey: KNZAIFIZJGFOCI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-N-Methylscopolamine from human M3 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.47, ALogP 2.82, HBA 7, HBD 2, PSA 115.04, QED 0.65
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XJOQXSSQHKPXSP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 407.38 nM (pChEMBL 6.389999866485596)
Descriptors: MW 415.5, ALogP 4.6, HBA 7, HBD 0, PSA 65.3, QED 0.44
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccnc(N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DBFMFHYDGXJVLJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 11.22 nM (pChEMBL 7.949999809265137)
Descriptors: MW 492.54, ALogP 3.61, HBA 10, HBD 1, PSA 117.1, QED 0.35
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: WDACLZKYOGTKNW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 18.2 nM (pChEMBL 7.739999771118164)
Descriptors: MW 418.5, ALogP 3.87, HBA 7, HBD 3, PSA 99.19, QED 0.4
Compound (SMILES): Cc1cccc(-c2cc(N)nc3[nH]cc(C#N)c23)c1
InChIKey: KWTGXMXCSXFSJX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 A2016T mutant phosphorylation at ser935 transfected in HEK293 cells after 48 hrs by in-cell Western assay
Measurement: IC50 = 471 nM (pChEMBL 6.329999923706055)
Descriptors: MW 248.29, ALogP 2.99, HBA 3, HBD 2, PSA 78.49, QED 0.69
Compound (SMILES): CNCCN1CCC(OCc2ccccc2)CC1
InChIKey: HBOJWAYLSJLULG-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 248.37, ALogP 1.89, HBA 3, HBD 1, PSA 24.5, QED 0.83
Compound (SMILES): COc1nc(N(CC(C)(C)F)c2cc(Cl)c(F)cc2F)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: RVMWIVNHZMXEHS-UWVGGRQHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide from human ERG expressed in HEK293 cells
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 457.84, ALogP 4.21, HBA 6, HBD 1, PSA 92.62, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(Cc2csc(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IIGRWRUGUUITMA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 472.57, ALogP 5.15, HBA 9, HBD 0, PSA 78.19, QED 0.32