lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOc1cc(N2CCN(S(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: XSXVTOKBIMMTQI-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 768.85, ALogP 6.53, HBA 11, HBD 2, PSA 143.29, QED 0.15
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cnc3[nH]ccc3n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMYSJBYJRVLWPM-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 516.57, ALogP 4.51, HBA 9, HBD 1, PSA 106.87, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC(F)CN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SBKRUFBQSKWUSE-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 436.49, ALogP 3.48, HBA 8, HBD 1, PSA 91.32, QED 0.45
Compound (SMILES): COc1cc(C2CCN(CCF)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: PWHFGNAWONSPIB-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 707.76, ALogP 7.9, HBA 9, HBD 2, PSA 105.91, QED 0.14
Compound (SMILES): COc1nc2ccc(C(C)(O)c3oc(C)nc3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
InChIKey: GZHHSXYGQHWIGF-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Reporter Assay: The reporter assay was performed by transiently transfecting HEK293T cells with 5 μg of pBIND-RORγt LBD or pBIND-RORγt LBD-AF2 and 5 μg pGL4.31 (Promega Cat no. C935A) using Fugene 6 (Invitrogen Cat no. E2691) at a 1:6 ratio of DNA:Fugene 6 in a T-75 flask in which cells were at least 80% confluent. Twenty four hours after bulk transfection, cells were plated into 96-well plates at 50,000 cells/well in phenol-red free DMEM containing 5% Lipid Reduced FCS and Pen/Strep. Six hours after plating, cells were treated with compounds for 24 hours. Media was removed and cells were lysed with 50 μL 1× Glo Lysis Buffer (Promega). Dual Glo Luciferase Reagent (50 μL/well) was then added and firefly luciferase luminescence was read on an Envision after a ten minute incubation. Finally, Stop and Glo reagent (50 μL/well) was added and renilla luciferase luminescence was read on an Envision after a ten minute incubation.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 490.91, ALogP 6.37, HBA 5, HBD 1, PSA 68.38, QED 0.35
Compound (SMILES): CC1CCN(C(=O)C(CCn2ccnc2[N+](=O)[O-])NS(=O)(=O)c2cc(Cl)c(N)c(Cl)c2)CC1
InChIKey: FVJCVTWWUJRNDE-UHFFFAOYSA-N
Target: C-C chemokine receptor type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P46092
Assay: Antagonist activity at human CCR10 expressed in CHOK1 cells coexpressing aequorin/Galphaq assessed as inhibition of human CCL28-dependent calcium flux by chemiluminescence assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 519.41, ALogP 2.68, HBA 8, HBD 2, PSA 153.46, QED 0.31
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCC4CCCCC4)[C@@H](C2)N(C)CC[C@]315
InChIKey: CROXCUGUTMDKDP-ZYGOFEOWSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Binding Assay: Binding assay of certain compounds of this invention to the opioid receptor was determine using radioligand binding assay (screening and dose-displacement).
Measurement: Ki = 89.96 nM (pChEMBL 7.050000190734863)
Descriptors: MW 467.65, ALogP 4.74, HBA 5, HBD 0, PSA 40.16, QED 0.6
Compound (SMILES): COc1cn(C(CC(C)C)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: PDLAMRDOLIUATC-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 493.95, ALogP 4.97, HBA 6, HBD 2, PSA 121.42, QED 0.46
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3c(C)cccn23)n1
InChIKey: LAVUQVGESJYCJA-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 807.93, ALogP 6.6, HBA 11, HBD 2, PSA 137.3, QED 0.16
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)c2cccc(F)c2n(C)c1=O
InChIKey: LEOYMYOSQPPAAS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos-B cells assessed as suppression of BCR/anti-IgG-stimulated Ca2+ flux after 1 hr incubation in dark by FLIPR1 assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 550.59, ALogP 4.76, HBA 6, HBD 3, PSA 123.11, QED 0.29
Compound (SMILES): COc1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1OC[C@@H]1CN2CCOC[C@H]2CO1
InChIKey: KHSJGHHCLKKKKU-KBPBESRZSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 509.37, ALogP 4.31, HBA 8, HBD 1, PSA 77.97, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC5(OC)CCNCC5)c4)nc3c2)c1
InChIKey: IJNFMKJSNQLEOT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.66, ALogP 4.83, HBA 9, HBD 1, PSA 86.56, QED 0.31
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(C(F)(F)F)cc4)ccc3o2)cc1)c1ccc(C(F)(F)F)cc1
InChIKey: RMPODXYECPUGCS-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 641.57, ALogP 7.13, HBA 6, HBD 2, PSA 118.37, QED 0.18
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(O)cc3F)CC2)C1
InChIKey: MFJNAWBKFSYMLB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 517.54, ALogP 3.64, HBA 7, HBD 2, PSA 114.07, QED 0.42
Compound (SMILES): CC(C)(C)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: BKVIUNNZVOCFGC-MRXNPFEDSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Agonist activity at human recombinant EP3A receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 = 19234 nM (pChEMBL 4.71999979019165)
Descriptors: MW 387.5, ALogP 4.46, HBA 4, HBD 1, PSA 66.84, QED 0.79
Compound (SMILES): O=C(O)C(=O)Nc1ccc2nc(NC(=O)c3cc(Br)c(Br)[nH]3)sc2c1
InChIKey: ZDVZBRWEKLWNNU-UHFFFAOYSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus DNA topoisomerase 4 using supercoiled pNO1 plasmid DNA as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 488.12, ALogP 3.42, HBA 5, HBD 4, PSA 124.18, QED 0.42
Compound (SMILES): Cc1cc(NC(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)n(C)n1
InChIKey: KVMNGYIMVRBSMH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 499.58, ALogP 2.48, HBA 9, HBD 2, PSA 136.58, QED 0.43
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(CCOC)c4)nc3c2)c1
InChIKey: AIVBMTJXLHCJTQ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.54, ALogP 2.64, HBA 9, HBD 2, PSA 114.63, QED 0.36
Compound (SMILES): CN1CCCN(c2cncc(-c3cc(CCO)no3)c2)CC1
InChIKey: ZDANANXJEHBAHQ-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Agonist activity at human alpha4beta2 nAChR expressed in human SH-EP1 cells after 9.5 mins by 86Rb+ efflux assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 302.38, ALogP 1.41, HBA 6, HBD 1, PSA 65.63, QED 0.92
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc4ccccc4s3)CC2)C1
InChIKey: CMBZNHSLRJYIHI-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 < 10 nM (pChEMBL 8)
Descriptors: MW 522.64, ALogP 4.27, HBA 8, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): C[C@]1(N2CCc3c(-c4cnc(N)nc4)nc(N4CCOCC4)nc32)CCN(S(C)(=O)=O)C1
InChIKey: ROYQBLPXACEGTQ-FQEVSTJZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 460.56, ALogP 0.14, HBA 10, HBD 1, PSA 130.67, QED 0.67
Compound (SMILES): COc1cc(OC)cc(N(CCN(C)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SDEGOUSDMNTQQS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.58, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.36
Compound (SMILES): Nc1nc(NCCc2ccc(O)cc2)nc2sc(-c3ccco3)nc12
InChIKey: PAERJGTURZDOCC-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity against human adenosine A2A receptor expressed in CHO cells assessed as inhibition of CGS21680-stimulated cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 353.41, ALogP 3.29, HBA 8, HBD 3, PSA 110.09, QED 0.5
Compound (SMILES): COc1c(Br)cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)cc1Br
InChIKey: DLIUAQISEFIHQE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 654.37, ALogP 4.58, HBA 8, HBD 1, PSA 115.96, QED 0.32
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)n3)CC2)C1
InChIKey: UTLSURCXUGWVFM-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 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): Cc1cc(F)ccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: OEOFVVDQHYJLBB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 513.58, ALogP 3.89, HBA 7, HBD 2, PSA 118.76, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCN5CCN(CCCO)CC5)c4)nc3c2)c1.Cl
InChIKey: RRKHYJVGAHJYAK-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 5495.41 nM (pChEMBL 5.260000228881836)
Descriptors: MW 585.75, ALogP 4.45, HBA 10, HBD 1, PSA 92.01, QED 0.23
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(F)c(F)cc12
InChIKey: NNNDNTAGOMPUOM-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 320.34, ALogP 3.09, HBA 3, HBD 1, PSA 45.33, QED 0.88
Compound (SMILES): NC(=O)n1cc(NC(=O)N2CCC[C@H]2C(=O)Nc2cccc(OC(F)(F)F)c2)c2ccccc21
InChIKey: GPEWMCZCFCZAEI-SFHVURJKSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 475.43, ALogP 4.1, HBA 5, HBD 3, PSA 118.69, QED 0.53
Compound (SMILES): CC1(C)CC(=O)N(CCCCN2Cc3ccccc3C2)C(=O)C1
InChIKey: HWHPJDOZGZLVJB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5-HT7 receptor by liquid scintillation counting method
Measurement: Ki = 739 nM (pChEMBL 6.130000114440918)
Descriptors: MW 314.43, ALogP 2.96, HBA 3, HBD 0, PSA 40.62, QED 0.62
Compound (SMILES): COc1cc(OC)cc(N(CCN)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: PJTVWSGDWBEDPC-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.45, ALogP 3.13, HBA 7, HBD 2, PSA 102.18, QED 0.5
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(Cl)cc(Cl)c3)CC2)C1
InChIKey: KSWJUVYIMSOFST-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 535.44, ALogP 4.36, HBA 7, HBD 1, PSA 106.73, QED 0.41
Compound (SMILES): Cn1cc(-c2cnc3ccc(N(CC4CC4)c4cccc(OC(F)F)c4)cc3n2)cn1
InChIKey: RVXVVMLZMQHZHP-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 421.45, ALogP 5.18, HBA 6, HBD 0, PSA 56.07, QED 0.41
Compound (SMILES): COCCNc1cc(NC(=O)N2CCCc3cc(CN4CCN(C)CC4=O)c(C=O)nc32)ncc1C#N
InChIKey: BHKDKKZMPODMIQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 V550L mutant (unknown origin)
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 506.57, ALogP 1.48, HBA 9, HBD 2, PSA 143.79, QED 0.4
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CC(=O)NC)c3)nc2c1.Cl
InChIKey: ZDXFCIBDTYOWRJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 475.55, ALogP 2.61, HBA 9, HBD 2, PSA 106.43, QED 0.36
Compound (SMILES): FC(F)(F)c1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)o1
InChIKey: YNUQOPRHHFOIIN-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 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 390.37, ALogP 3.6, HBA 6, HBD 1, PSA 75.25, QED 0.58
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC[C@@H]2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: GIXXSGFKMGLYQT-BDQAORGHSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 0.5888 nM (pChEMBL 9.229999542236328)
Descriptors: MW 486.62, ALogP 5.06, HBA 8, HBD 0, PSA 68.54, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CMTCHQUJHUVRIU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.47 nM (pChEMBL 7.980000019073486)
Descriptors: MW 491.56, ALogP 4.21, HBA 9, HBD 1, PSA 104.21, QED 0.35
Compound (SMILES): COc1cc(OC)cc(N(C/C=C\c2ncccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DULFLBNKXBAPSF-XQRVVYSFSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 18.2 nM (pChEMBL 7.739999771118164)
Descriptors: MW 479.54, ALogP 4.69, HBA 9, HBD 0, PSA 91.08, QED 0.32
Compound (SMILES): OC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: PAMGOJDAOVYVMB-MGCOHNPYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
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 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 271.32, ALogP 1.87, HBA 5, HBD 2, PSA 79.1, QED 0.75
Compound (SMILES): CC1CN(C(=O)c2cc(Cc3n[nH]c(=O)c4ccccc34)ccc2F)Cc2nnc(C(F)(F)F)n21
InChIKey: QNQFPYADHVFRKQ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Enzyme Assay: In order to test the selectivity of substituents on piperazinotriazole ring within the PARP family, the selectivity of compound S3 and positive compound AZD2281 were tested.
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 486.43, ALogP 3.48, HBA 6, HBD 1, PSA 96.77, QED 0.45
Compound (SMILES): N#Cc1cc(C(F)(F)F)ccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)c(Cl)cc21
InChIKey: SHCCRGIIPVJFHB-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Mus musculus
UniProt: Q62205
Assay: Inhibition of mouse NaV1.7 by whole cell voltage clamp method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 500.91, ALogP 5.02, HBA 7, HBD 1, PSA 95.32, QED 0.54
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NYYKCMGNIZNHAN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.607 nM (pChEMBL 8.180000305175781)
Descriptors: MW 516.52, ALogP 3.7, HBA 9, HBD 2, PSA 97.56, QED 0.33
Compound (SMILES): Cc1cc(C)c(-n2ccn3nc(-c4cccnc4)cc23)cc1NC(=O)c1cc(C#N)cc(S(F)(F)(F)(F)F)c1
InChIKey: MPASHPJAIUOWCK-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Binding affinity to TIE2 (unknown origin) assessed as dissociation constant by KINOME scan assay
Measurement: Kd = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 558.54, ALogP 7.59, HBA 6, HBD 1, PSA 88.01, QED 0.23
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CLPZHWNOBVVCEB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 499.62, ALogP 4.02, HBA 8, HBD 1, PSA 88.41, QED 0.37
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(S(N)(=O)=O)cc4)cc23)c1F
InChIKey: NZJIFYMUDPMWAG-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 534.57, ALogP 3.54, HBA 6, HBD 3, PSA 152.08, QED 0.29
Compound (SMILES): Cc1cc(F)cc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c12
InChIKey: HEMPDMBOSVBORY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 316.38, ALogP 3.26, HBA 3, HBD 1, PSA 45.33, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC[C@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MJBNLVZGJYYOOP-NRFANRHFSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 488.59, ALogP 3.64, HBA 9, HBD 1, PSA 88.77, QED 0.38
Compound (SMILES): CCO[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2Oc1cc2ncnc(Nc3ccc(Br)c(Cl)c3)c2cc1OC
InChIKey: RVMLSAUWFLLGAT-FNAHDJPLSA-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 536.81, ALogP 4.75, HBA 8, HBD 1, PSA 83.96, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CC(O)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KTQNUSVVKAQAIV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 0.4467 nM (pChEMBL 9.350000381469727)
Descriptors: MW 474.57, ALogP 3.25, HBA 9, HBD 1, PSA 88.77, QED 0.4
Compound (SMILES): COc1cc(O)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ORUNGMOTBJGTPU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.074 nM (pChEMBL 8.390000343322754)
Descriptors: MW 401.47, ALogP 4.29, HBA 7, HBD 1, PSA 76.3, QED 0.52
Compound (SMILES): Cc1c(-c2c(F)cc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)[nH]c2c(F)cccc2c1=O
InChIKey: SXAGMGAWHSROAH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Tyrosine Kinase Assay: The assays were performed in V-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2, 25 mM beta-glycerolphosphate, 0.015% Brij 35 surfactant and 4 mM DTT). The reaction was initiated by the combination of Jak2 tyrosine kinase with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 minutes and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 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 vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays is ATP, 30 μM; Jak2 fluorescent peptide, 1.5 μM; Jak2, 1 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations, each in duplicate.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 554.55, ALogP 4.89, HBA 5, HBD 4, PSA 133.97, QED 0.25
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(S(=O)(=O)NC5CC5)cc4)cc23)c1F
InChIKey: YNFCDXLGHFKDKE-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 574.63, ALogP 4.33, HBA 6, HBD 3, PSA 138.09, QED 0.24
Compound (SMILES): O=C(CCNC(=O)c1ccc(Cl)s1)Nc1ccc(N2CCOCC2=O)c(C(F)(F)F)c1
InChIKey: KPMMXXOLUHKIMC-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 30 min pre-incubation of enzyme with compound and 45 min reaction time after substrate addition.
Measurement: IC50 = 3.93 nM (pChEMBL 8.40999984741211)
Descriptors: MW 475.88, ALogP 3.54, HBA 5, HBD 2, PSA 87.74, QED 0.67
Compound (SMILES): O=C(O)[C@@H]1C[C@@H]2[C@H](C1)[C@H]2C(=O)N1CC[C@](c2ccc(C(F)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: MVMNXAJUCHJIFB-LPSQLEIASA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Transactivation of human GAL4-fused LXRbeta expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 625.53, ALogP 5.37, HBA 4, HBD 1, PSA 91.75, QED 0.34
Compound (SMILES): Cc1nc2ccc(-n3ncc(C(=O)c4cc5ccccc5[nH]4)c3N)cc2[nH]1
InChIKey: BEMNJULZEQTDJY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells assessed as reduction in channel currents at -80 mV holding potential by automated whole-cell patch clamp method
Measurement: IC50 = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 356.39, ALogP 3.35, HBA 5, HBD 3, PSA 105.38, QED 0.43
Compound (SMILES): COc1cc(OCCO)cc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: BXBWZDDZLDSYQH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 15.49 nM (pChEMBL 7.809999942779541)
Descriptors: MW 431.5, ALogP 3.95, HBA 7, HBD 2, PSA 96.39, QED 0.41
Compound (SMILES): Cn1cc(-c2cnc3ccc(N(CC4CC4)c4ccccc4)cc3n2)cn1
InChIKey: VDVZOCBAFGDAKS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 354.81 nM (pChEMBL 6.449999809265137)
Descriptors: MW 355.45, ALogP 4.58, HBA 5, HBD 0, PSA 46.84, QED 0.53
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: GEEWFYSWIUQFGV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.677 nM (pChEMBL 8.329999923706055)
Descriptors: MW 472.55, ALogP 3.8, HBA 8, HBD 1, PSA 94.4, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccc(Cl)nc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AUFUDTOCLCOVHF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.02 nM (pChEMBL 8.520000457763672)
Descriptors: MW 486.96, ALogP 5.43, HBA 8, HBD 0, PSA 78.19, QED 0.28
Compound (SMILES): CC(F)c1noc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)C3C)n1
InChIKey: UECKJWCZXJBAJH-UHFFFAOYSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Binding Assay: The affinity of compounds of the invention for the NK-2 receptor was evaluated in CHO recombinant cells which express the human NK-2 receptor. Membrane suspensions were prepared from these cells. The following radioligand [125I]-Neurokinin A (PerkinElmer Cat#NEX252) was used in this assay. Binding assays were performed in a 25 mM HEPES/1 mM CaCl2/5 mM MgCl2/0.5% BSA/10 μg/ml saponin, at pH 7.4. Binding assays consisted of 25 μl of membrane suspension (approximately 3.75 μg of protein/well in a 96 well plate), 50 μl of compound or reference ligand (Neurokinin A) at increasing concentrations (diluted in assay buffer) and 0.1 nM [125I]-Neurokinin A. The plate was incubated 60 min at 25° C. in a water bath and then filtered over GF/C filters (Perkin Elmer, 6005174, presoaked in assay buffer without saponine for 2 h at room temperature) with a Filtration unit (Perkin Elmer). The radioactivity retained on the filters was measured by using the TopCount-NXT reader (Packard).
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 374.35, ALogP 2.71, HBA 7, HBD 0, PSA 89.94, QED 0.7
Compound (SMILES): COc1cc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2cc1F
InChIKey: RBKJRFRDZLFTTM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
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 332.38, ALogP 2.96, HBA 4, HBD 1, PSA 54.56, QED 0.87
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCCN1CCCCC1
InChIKey: QOLKGXDWVMWHLS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
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 447.37, ALogP 5.55, HBA 6, HBD 1, PSA 59.51, QED 0.51
Compound (SMILES): COC[C@@H](CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)OC(C)=O
InChIKey: BFLRXUQCNYUNBN-HSZRJFAPSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 491.55, ALogP 3.76, HBA 10, HBD 0, PSA 100.83, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cnc3[nH]ccc3n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMYSJBYJRVLWPM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 516.57, ALogP 4.51, HBA 9, HBD 1, PSA 106.87, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC(F)CN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SBKRUFBQSKWUSE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.862 nM (pChEMBL 8.729999542236328)
Descriptors: MW 436.49, ALogP 3.48, HBA 8, HBD 1, PSA 91.32, QED 0.45
Compound (SMILES): CC1CCN(C(=O)C(CCn2ccnc2[N+](=O)[O-])NS(=O)(=O)c2cc(Cl)c(N)c(Cl)c2)CC1
InChIKey: FVJCVTWWUJRNDE-UHFFFAOYSA-N
Target: C-C chemokine receptor type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P46092
Assay: Antagonist activity at human CCR10 expressed in CHOK1 cells coexpressing aequorin/Galphaq assessed as inhibition of human CCL27-dependent calcium flux in presence of coelenterazine H by chemiluminescence assay
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 519.41, ALogP 2.68, HBA 8, HBD 2, PSA 153.46, QED 0.31
Compound (SMILES): COc1cn(C(CC(C)C)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: PDLAMRDOLIUATC-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 493.95, ALogP 4.97, HBA 6, HBD 2, PSA 121.42, QED 0.46
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)c2cccc(F)c2n(C)c1=O
InChIKey: LEOYMYOSQPPAAS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood assessed as suppression of BCR/anti-IgM/IgG-stimulated CD69 surface expression after 18 hrs with agitation by FITC-staining based FACS analysis
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 550.59, ALogP 4.76, HBA 6, HBD 3, PSA 123.11, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC5(OC)CCNCC5)c4)nc3c2)c1
InChIKey: IJNFMKJSNQLEOT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 528.66, ALogP 4.83, HBA 9, HBD 1, PSA 86.56, QED 0.31
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(C(F)(F)F)cc4)ccc3o2)cc1)c1ccc(C(F)(F)F)cc1
InChIKey: RMPODXYECPUGCS-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL/ES-mediated refolding of the denatured malate dehydrogenase
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 641.57, ALogP 7.13, HBA 6, HBD 2, PSA 118.37, QED 0.18
Compound (SMILES): CC(C)(C)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: BKVIUNNZVOCFGC-MRXNPFEDSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Agonist activity at human recombinant EP4 receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 387.5, ALogP 4.46, HBA 4, HBD 1, PSA 66.84, QED 0.79
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(CCOC)c4)nc3c2)c1
InChIKey: AIVBMTJXLHCJTQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 476.54, ALogP 2.64, HBA 9, HBD 2, PSA 114.63, QED 0.36
Compound (SMILES): CN1CCCN(c2cncc(-c3cc(CCO)no3)c2)CC1
InChIKey: ZDANANXJEHBAHQ-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Antagonist activity at human alpha4beta2 expressed in human SH-EP1 cells assessed as reduction in carbamylcholine induced 86Rb+ efflux preincubated for 10 mins followed by carbamylcholine addition measured after 5 mins by Cherenkov counting
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 302.38, ALogP 1.41, HBA 6, HBD 1, PSA 65.63, QED 0.92
Compound (SMILES): COc1cc(OC)cc(N(CCN(C)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SDEGOUSDMNTQQS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.413 nM (pChEMBL 8.850000381469727)
Descriptors: MW 460.58, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.36