lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1c(C(=O)N2CCc3c(nnn3-c3cnccn3)C2C)cccc1C(F)(F)F
InChIKey: UMGZTIJCJJGATI-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Ca2+ Flux Assay: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat) or 600 μM (mouse)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of test concentration.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 402.38, ALogP 3.14, HBA 6, HBD 0, PSA 76.8, QED 0.66
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC[C@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LKMLECIRYJPQOC-QFIPXVFZSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 502.62, ALogP 4.03, HBA 9, HBD 1, PSA 88.77, QED 0.35
Compound (SMILES): CCc1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: HQQABXMYFDMKIT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 7585.78 nM (pChEMBL 5.119999885559082)
Descriptors: MW 505.58, ALogP 4.59, HBA 9, HBD 0, PSA 91.08, QED 0.3
Compound (SMILES): CO[C@H]1C[C@@H](n2c(=O)n(C)c3cnc4ccc(-c5ccc(OCCCN(C)C)nc5)cc4c32)C1
InChIKey: DWICJHMMZLNUEB-BGYRXZFFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology assay
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 461.57, ALogP 3.63, HBA 8, HBD 0, PSA 74.41, QED 0.37
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(nnn2-c2ccccc2)C1
InChIKey: SQRLNRNKCKCMFY-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Ca2+ flux assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 1874 nM (pChEMBL 5.730000019073486)
Descriptors: MW 406.8, ALogP 4.14, HBA 4, HBD 0, PSA 51.02, QED 0.64
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)CC1
InChIKey: RNOAOAWBMHREKO-QFIPXVFZSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of full-length N-terminal GST-tagged ITK (2 to 620 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 65.9 nM (pChEMBL 7.179999828338623)
Descriptors: MW 471.56, ALogP 4.22, HBA 6, HBD 2, PSA 102.48, QED 0.52
Compound (SMILES): CNc1cccc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VCHBCVRCEHYVAE-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 4786.3 nM (pChEMBL 5.320000171661377)
Descriptors: MW 384.49, ALogP 4.62, HBA 6, HBD 1, PSA 58.87, QED 0.53
Compound (SMILES): Cc1ncoc1-c1nnc(SCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: KLQDZSYTMPJBBU-UTKZUKDTSA-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 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 463.53, ALogP 4.77, HBA 7, HBD 0, PSA 59.98, QED 0.49
Compound (SMILES): COc1cc(N2CCC(N3CCC(O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: MRHINXBPDMMURR-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 760.85, ALogP 7.18, HBA 11, HBD 3, PSA 129.38, QED 0.13
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JRZBGTIYYHVJEO-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 434.5, ALogP 2.51, HBA 9, HBD 2, PSA 111.55, QED 0.44
Compound (SMILES): N#CCC1(n2cc(-c3c(C#N)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(C#N)cc(C#N)c3)CC2)C1
InChIKey: AOWQKMUADIXHEC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 540.59, ALogP 3.27, HBA 9, HBD 1, PSA 165.21, QED 0.4
Compound (SMILES): Cc1c(C(=O)N2Cc3nnn(-c4ncc(F)cn4)c3C[C@@H]2C)ccnc1C(F)(F)F
InChIKey: VYDQRUVOXRXKGT-VIFPVBQESA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 421.36, ALogP 2.51, HBA 7, HBD 0, PSA 89.69, QED 0.59
Compound (SMILES): CCN(CC)c1ccc(-c2cc(-c3ccc(C(=O)O)cc3)ccc2OCCO)cc1C(C)(C)C
InChIKey: OOTHJAQLAQMOBN-UHFFFAOYSA-N
Target: Retinoic acid receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10276
Assay: Agonist activity at GAL4 DNA-binding domain-tagged RARalpha (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 1010 nM (pChEMBL 6)
Descriptors: MW 461.6, ALogP 6.23, HBA 4, HBD 2, PSA 70, QED 0.4
Compound (SMILES): CO[C@H]1C[C@@H](n2c(=O)n(C)c3cnc4ccc(-c5ccc(OCCCN6CCCC6)nc5)cc4c32)C1
InChIKey: OPNZWUZVFPAJIO-SZPZYZBQSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT29 cells assessed as decrease in Chk1 phosphorylation at Ser 345 preincubated for 1 hr followed by 4NQO addition and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay
Measurement: IC50 > 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 487.6, ALogP 4.16, HBA 8, HBD 0, PSA 74.41, QED 0.35
Compound (SMILES): CO[C@H]1CC[C@]2(CC1)Cc1ccc(-c3cc(Br)cc(C#N)c3)cc1C21N=C(C)C(N)=N1
InChIKey: BCPJXJSUDZCZSL-TYRCWPPYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: sAPPbeta Release Assay: SH-SY5Y cells were cultured in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids and cryopreserved and stored at −140° C. at a concentration of 7.5-9.5×106 cells per vial. Thaw cells and seed at a conc. of around 10000 cells/well in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids to a 384-well tissue culture treated plate, 100 μL cell susp/well. The cell plates were then incubated for 7-24 h at 37° C., 5% CO2. The cell medium was removed, followed by addition of 30 μL compound diluted in DMEM/F-12 with Glutamax, 10% FCS, 1% non-essential amino acids and 1% PeSt to a final conc. of 1% DMSO. The compounds were incubated with the cells for 17 h (overnight) at 37° C., 5% CO2. Meso Scale Discovery (MSD) plates were used for the detection of sAPPβ release. MSD sAPPβ plates were blocked in 1% BSA in Tris wash buffer (40 μL/well) for 1 h on shake at r.t. and washed 1 time in Tris wash buffer (40 μL/well). 20 μL of medium was transferred to the pre-blocked and washed MSD sAPPβ microplates, and the cell plates were further used in an ATP assay to measure cytotoxicity. The MSD plates were incubated with shaking at r.t. for 2 h and the media discarded. 10 μL detection antibody was added (1 nM) per well followed by incubation with shaking at r.t. for 2 h and then discarded. 40 μL Read Buffer was added per well and the plates were read in a SECTOR Imager.
Measurement: IC50 = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 477.41, ALogP 5.1, HBA 5, HBD 1, PSA 83.76, QED 0.65
Compound (SMILES): Cn1cc(-c2cc3c(cn2)cnn3-c2cccc(N3CCNCC(O)C3)n2)cn1
InChIKey: WHGGAJVOOZRMSO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Kinase Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.PIM reactions were carried out in a final volume of 10 uL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 uL 2Ã¿Â¿ATP and test compound to 5 uL of 2x enzyme and FAM-peptide, contained 20 uM PIM1, 50 uM PIM2, or 55 uM PIM3, 1 uM FAM-peptide, and 10 uM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 uL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000 (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of -500V, an upstream voltage of -2150V, and a screening pressure of -1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm. Substrate conversion was calculated from the electropherogram using HTS Well Analyzer software (Caliper Life Sciences, Hopkinton, Mass.). Ki values for the test compound were calculated.
Measurement: Ki = 0.131 nM (pChEMBL 9.880000114440918)
Descriptors: MW 390.45, ALogP 0.99, HBA 9, HBD 2, PSA 96.92, QED 0.54
Compound (SMILES): COc1cc2c(Nc3cccc(Cl)c3F)ncnc2cc1O[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2F
InChIKey: GBVHHGINCYVVRZ-TVJWEXTRSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 449.84, ALogP 4.06, HBA 7, HBD 1, PSA 74.73, QED 0.63
Compound (SMILES): N#Cc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)s1
InChIKey: GLTHTYRWIILEGV-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 363.45, ALogP 2.92, HBA 7, HBD 1, PSA 85.9, QED 0.6
Compound (SMILES): C#CC(=O)Nc1cccc(-c2cnc3[nH]cc(Cl)c3c2)n1
InChIKey: DZAHHFCGFLVKIL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 296.72, ALogP 2.85, HBA 3, HBD 2, PSA 70.67, QED 0.71
Compound (SMILES): Cc1cncc(-c2cc3c(cn2)cnn3-c2cccc(N3CCNC(C)C3)n2)n1
InChIKey: BVSPZNRNBYKDLE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.PIM reactions were carried out in a final volume of 10 uL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 uL 2Ã¿Â¿ATP and test compound to 5 uL of 2x enzyme and FAM-peptide, contained 20 uM PIM1, 50 uM PIM2, or 55 uM PIM3, 1 uM FAM-peptide, and 10 uM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 uL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000 (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of -500V, an upstream voltage of -2150V, and a screening pressure of -1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm. Substrate conversion was calculated from the electropherogram using HTS Well Analyzer software (Caliper Life Sciences, Hopkinton, Mass.). Ki values for the test compound were calculated.
Measurement: Ki = 0.54 nM (pChEMBL 9.270000457763672)
Descriptors: MW 386.46, ALogP 2.38, HBA 8, HBD 1, PSA 84.65, QED 0.58
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccccc3Cl)CC2)C1
InChIKey: OSKNEJAXRNEFRX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 516.01, ALogP 4.1, HBA 7, HBD 2, PSA 118.76, QED 0.41
Compound (SMILES): COc1cc(N2CCN(C3CCN(CCF)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: WROBOUZJBUWDDO-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 761.85, ALogP 7.3, HBA 10, HBD 2, PSA 103.16, QED 0.14
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4CN(C)C)nc3c2)c1
InChIKey: CCDNYIWGTYFDSI-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 503.65, ALogP 4.25, HBA 9, HBD 1, PSA 80.57, QED 0.33
Compound (SMILES): CCC1(C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CCS(=O)(=O)CC1
InChIKey: HQZCXDWOMVTYLT-DEOSSOPVSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human Gal4-fused RORbeta LBD (200 to 559 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 661.63, ALogP 5.62, HBA 5, HBD 0, PSA 88.59, QED 0.3
Compound (SMILES): CCOc1ccc(-c2nc3ccccn3c2-c2ccnc(Nc3ccc(N4CCN(CCOC)CC4)cc3OC)n2)cc1C(=O)Nc1c(F)cccc1F
InChIKey: YFQKRLUWZVQGQS-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 734.81, ALogP 6.91, HBA 11, HBD 2, PSA 118.38, QED 0.13
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(-c2nc3cc(NS(=O)(=O)CCC)ccc3o2)cc1
InChIKey: MUSNXRCOWVRSMH-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 437.54, ALogP 3.8, HBA 6, HBD 2, PSA 118.37, QED 0.53
Compound (SMILES): CC(C)Oc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(C)CCO1
InChIKey: HPSOKGKCQBAFCF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 477.39, ALogP 5.18, HBA 7, HBD 1, PSA 68.74, QED 0.5
Compound (SMILES): CCCN1CCC(c2cc(OC)c(Nc3nccc(-c4c(-c5ccc(OC)c(C(=O)Nc6c(F)cccc6F)c5)nc5ccccn45)n3)cc2C)CC1
InChIKey: YXAQENFRPVZZLS-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 717.82, ALogP 8.65, HBA 9, HBD 2, PSA 105.91, QED 0.14
Compound (SMILES): c1cnc2ncn(-c3cc(Nc4ccc(OCCN5CCCCC5)cn4)ncn3)c2c1
InChIKey: CODOEMQMKTTYRW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TAO1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7L7X3
Assay: Inhibition recombinant human TAOK1 (1 to 356 residues) after 5 mins in presence of [33P] ATP by Topcount method
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 416.49, ALogP 3.21, HBA 9, HBD 1, PSA 93.88, QED 0.49
Compound (SMILES): Nc1nc(NCCN2CCC(c3ccccc3)CC2)nc2nc(-c3ccco3)nn12
InChIKey: WUOOFKSGLYZAKD-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: The A2A-StaR2 receptor has been purified from membranes in n-decyl-beta-D-maltoside as detergent. Ligands were prepared over a five-fold concentration series and injected in either a multi- or a single-cycle format depending on the kinetic parameters of the ligand. The actual concentrations as well as contact and dissociation times varied between the ligands depended on the kinetics and affinity of the interaction. The data were fitted to a 1:1 interaction model using the kinetics evaluation software from Biacore. A minimum of three measurements were recorded for each interaction.
Measurement: Kd = 8.22 nM (pChEMBL 8.09000015258789)
Descriptors: MW 404.48, ALogP 2.65, HBA 9, HBD 2, PSA 110.4, QED 0.5
Compound (SMILES): CCOc1cc(N2CCN(C(C)C)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: GGCSJXJBJIBXQQ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 718.81, ALogP 7.67, HBA 10, HBD 2, PSA 109.15, QED 0.14
Compound (SMILES): Cc1cc(Nc2cc(C)c(C#N)c(NCCOc3cccnc3C)n2)n[nH]1
InChIKey: VQBZFHKHISYRMO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 363.43, ALogP 3.23, HBA 7, HBD 3, PSA 111.54, QED 0.55
Compound (SMILES): COc1cnc(C(=O)Nc2ccc(F)c([C@]3(C)CS(=O)(=O)C(C)(C)C(N)=N3)c2)cn1
InChIKey: HVMRBCNORJDLCW-IBGZPJMESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK cells by voltage clamp assay
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 435.48, ALogP 1.66, HBA 8, HBD 2, PSA 136.63, QED 0.74
Compound (SMILES): N[C@H](C(=O)O)[C@H](NS(=O)(=O)c1ccccc1)C(=O)O
InChIKey: ZHWUOFGFENMPFS-YUMQZZPRSA-N
Target: Excitatory amino acid transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P43003
Assay: Inhibition of [3H]-D-Asp uptake at human EAAT1 expressed in HEK293 cells measured after 3 mins by TopCount method
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 288.28, ALogP -1.17, HBA 5, HBD 4, PSA 146.79, QED 0.52
Compound (SMILES): CN(CCO)c1ncc(C(=O)Nc2ccc(OC(F)(F)Cl)cc2)cc1-c1cncc(C#N)c1
InChIKey: XKRULHQNJBGDON-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Cellular Proliferation Assay: Test compounds were resuspended in DMSO at a concentration of 10 mM. A serial three-fold dilution of each compound with DMSO was performed in 384-well plates using the Janus Liquid Dispenser (PerkinElmer). Compound was delivered to the assay plates containing 2500 cells in a 50 μL volume via Acoustic delivery from an ATS-100 (EDC). For Ba/F3-BCR-ABL1-WT cell assays, 2 nL of each compound dilution was transferred to the assay plate for final assay concentrations of 0.4 μM, 0.13 μM, 0.044 μM, 0.015 μM, 0.005 μM, 0.001 μM, 0.00033 μM, 0.00011 μM, 0.000037 μM, 0.000012 μM. For Ba/F3-WT and Ba/F3-BCR-ABL1-T315I cell assays, 50 nL of each compound dilution was transferred to the assay plate for final assay concentrations of 10 μM, 3.33 μM, 1.11 μM, 0.37 μM, 0.12 μM, 0.041 μM, 0.014 μM, 0.0046 μM, 0.0015 μM, 0.00051 μM.Cells were incubated at 37° C. in a humidified environment with 5% car
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 473.87, ALogP 3.86, HBA 7, HBD 2, PSA 111.37, QED 0.48
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCN(CCO)CC5)c4)nc3c2)c1.Cl
InChIKey: VODOUHVUVVFGNL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 6165.95 nM (pChEMBL 5.210000038146973)
Descriptors: MW 557.7, ALogP 3.67, HBA 10, HBD 1, PSA 92.01, QED 0.28
Compound (SMILES): CCOC(=O)C(C)N1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: BTGGKWOJEKOLEQ-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 535.43, ALogP 4.72, HBA 9, HBD 1, PSA 95.04, QED 0.39
Compound (SMILES): CN(C)Cc1cc(C#N)cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c1
InChIKey: RHYNNSFSDRXQLO-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 > 100 nM (pChEMBL 7)
Descriptors: MW 548.66, ALogP 2.98, HBA 9, HBD 1, PSA 133.76, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CCCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RFPQZVZQZKKHQS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.47
Compound (SMILES): COc1ccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NC(=O)C2CC2)cn1
InChIKey: YDRQCGICZKAGCQ-LMKMVOKYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Displacement of 3H-aldosterone from MR (unknown origin) ligand binding domain by SPA assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.51, ALogP 4.6, HBA 6, HBD 1, PSA 78.27, QED 0.42
Compound (SMILES): COc1cc(N2CCC(N3CCC(F)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: NFLQLTNOVWJRID-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 732.81, ALogP 8.14, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): N#C[C@@H]1CCCN1C(=O)CNC(=O)c1cnc2ccccc2c1
InChIKey: HNRNBVNSDXARCW-AWEZNQCLSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Enzymatic Assay: Enzyme activities were determined kinetically in a final volume of 200 μl for 10 minutes at 37° C. by measuring the initial velocities of pNA release (405 nm) from the substrate using a Spectramax plus microtiterplate reader (Molecular devices). One unit of enzyme activity was defined as the amount of enzyme that catalyzes the release of 1 μmol pNA from the substrate per minute under assay conditions. The chromogenic substrate Gly-Pro-p-nitroanilide (100 μmol/l) was used at pH 8.3 for DPP IV, Lys-Ala-p-nitroanilide (1 mmol/l) at pH 5.5 for DPP II, Ala-Pro-p-nitroanilide (300 μmol/l) at pH 7.4 for DPP9 and Ala-Pro-p-nitroanilide (2 mmol/l) at pH 7.4 for FAP activity measurement. To evaluate the endopeptidase activity of FAP and the influence of inhibitors thereon, Z-Gly-Pro-AMC and Z-Gly-Pro-p-nitroanilide were used at a final concentration of 300 and 100 μmol/l, respectively. The substrate concentrations were chosen around the Km value obtained under the assay conditions used. Buffer compositions for the DPP assays were reported before in the purification articles−vide supra. The FAP assay buffer consisted of 50 mM Tris pH7.4 containing 100 mmol/l NaCl and 0.1 mg/ml bovine serum albumin. The PREP activity was measured as described by Brandt et al. using the chromogenic substrate Z-Gly-Pro-p-nitroanilide (0.25 mmol/l) at pH 7.5 in the presence of 10 mmol/l DTT. Test compounds were dissolved and diluted in DMSO (final concentration DMSO during assay 5% v/v) except for FAP where dilution of the inhibitor was done in water. Inhibitors are pre-incubated with the enzyme for 15 min at 37° C. before starting the assay by the addition of substrate. The concentration of enzyme and of inhibitor during the preincubation is double of the final concentration during activity measurement.
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 308.34, ALogP 1.48, HBA 4, HBD 1, PSA 86.09, QED 0.93
Compound (SMILES): COc1cc(-c2cc(OC)c(-n3c(=O)ccc4cc(S(=O)(=O)Nc5ncccn5)ccc43)cc2F)ccc1Cl
InChIKey: ZHGZIHUZNQBPHC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Time-dependent inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated with enzyme in presence of NADPH followed by substrate addition
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 567, ALogP 5.06, HBA 8, HBD 1, PSA 112.41, QED 0.29
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CC3CCC(C2)N3C(=O)c2cc(F)cc(C#N)c2)C1
InChIKey: QSPJYULZDWYAEG-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 535.59, ALogP 3.59, HBA 8, HBD 1, PSA 130.52, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(CCNCC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GIWGPTOTMRZIBE-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 458.57, ALogP 4.19, HBA 8, HBD 1, PSA 77.33, QED 0.36
Compound (SMILES): C#CCN(c1ccc2ncc(-c3cnn(C)c3)nc2c1)c1c(F)c(OC)cc(OC)c1F
InChIKey: MXMLJQCILGAGCP-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 435.43, ALogP 4.1, HBA 7, HBD 0, PSA 65.3, QED 0.43
Compound (SMILES): Nc1nc(NCCc2ccccc2)nc2sc(-c3ccco3)nc12
InChIKey: UNFCWBZGDOODJH-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 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 337.41, ALogP 3.58, HBA 7, HBD 2, PSA 89.86, QED 0.58
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: MNAFRWGRFIBAQX-GCJKJVERSA-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 477.56, ALogP 5.16, HBA 7, HBD 0, PSA 59.98, QED 0.35
Compound (SMILES): S=c1[nH]c(C2CCCCC2)c2c3cc[nH]c3ncn12
InChIKey: MZSZFDGQDHRGQK-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 272.38, ALogP 3.92, HBA 3, HBD 2, PSA 48.88, QED 0.66
Compound (SMILES): C=CCOc1cc(-c2ccc3c(/C=C/c4ccc(OC)c(OC)c4)n[nH]c3c2)ccc1O
InChIKey: BXMUFQGDIWSQBJ-BJMVGYQFSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human GST-tagged CDK4/cyclin D1 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by gamma32P-ATP based scintillation counting analysis
Measurement: Ki = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 428.49, ALogP 5.69, HBA 5, HBD 2, PSA 76.6, QED 0.35
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cccc(S(C)(=O)=O)c4)cc23)c1F
InChIKey: LCVHYZOPJTTYEL-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 533.58, ALogP 4.29, HBA 6, HBD 2, PSA 126.06, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCCNC(=O)C(C)(O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: KFJOXEZTTGGPOW-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 558.56, ALogP 4.01, HBA 9, HBD 2, PSA 114.63, QED 0.28
Compound (SMILES): CCC[C@]1(C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC[C@H](C(=O)O)CC1
InChIKey: SJFLTEYVNDWHPL-DOYMOWJKSA-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 669.63, ALogP 7.08, HBA 4, HBD 1, PSA 91.75, QED 0.24
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4CCO)nc3c2)c1
InChIKey: KGJGNTKVAMGHGP-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 449.51, ALogP 2.71, HBA 9, HBD 2, PSA 105.76, QED 0.4
Compound (SMILES): Nc1nc2cc(-c3ccc4ncc(C(=O)N5CCOCC5)n4c3)ccc2o1
InChIKey: BLGWHBSBBJNKJO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 15 mins in presence of NADPH by LC/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.38, ALogP 2.2, HBA 7, HBD 1, PSA 98.89, QED 0.59
Compound (SMILES): COc1cc(OCCO)cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ALWLHZIHFJJPNH-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 449.51, ALogP 2.93, HBA 9, HBD 2, PSA 105.76, QED 0.38
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3cnc(C)nc3)nc3cc(C)ccn23)c(C#Cc2ccc3c(ccc(=O)n3C)c2)n1
InChIKey: KNODPLACRRUGBI-NRFANRHFSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 582.67, ALogP 4.27, HBA 9, HBD 2, PSA 119.1, QED 0.29
Compound (SMILES): O=C(NO)c1cnc(NC2(c3ccccc3)CCC(F)(F)CC2)nc1
InChIKey: MRWCVKLVSWYIFO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human BEAS-2B cells assessed as deacetylation of acetylated alpha-tubulin level incubated for 24 hrs by Western blot analysis
Measurement: EC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 348.35, ALogP 3.11, HBA 5, HBD 3, PSA 87.14, QED 0.58
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(N2CCOCC2)no1
InChIKey: DACWWGSNTVRALQ-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 503.35, ALogP 4.49, HBA 10, HBD 1, PSA 107.66, QED 0.39
Compound (SMILES): COc1cn(C(C[C@@H]2CCCO2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: AETBCOOBUYAHJM-AJZOCDQUSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition Assay: 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 Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 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 substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μl 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).
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 521.96, ALogP 4.5, HBA 7, HBD 2, PSA 130.65, QED 0.45
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#Cc1ccc(F)cn1)c1nc2cccc(Cl)c2c(=O)n1N1CCNCC1
InChIKey: GMYFMBWBTPKFFS-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: TR-FRET PIK3 Assay: TR-FRET monitored the formation of 3,4,5-inositol triphosphate molecule that competed with fluorescently labeled PIPS for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidylinositide 3-phosphate product resulted in a decrease in TR-FRET signal as the labeled fluorophore was displaced from the GRP-1 protein binding site.Class I PI3K isoforms were expressed and purified as heterodimeric recombinant proteins. All assay reagents and buffers for the TR-FRET assay were purchased from Millipore. PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2× Km ATP (75-500 μM), 2 μM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, and 1% (v/v) DMSO at the following concentrations for each isoform: PI3Kα, PI3Kβ, and PI3Kδ between 25 and 50 pM, and PI3Kγ at 2 nM. The compounds of Table 1 and Compound X ((S)-2,4-diamino-6-((1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile) were added to the assay solution and incubated for 30 minutes at 25° C. The reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIPS, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 100 is delay and 500 is read window).The results were normalized based on positive (1 μM wortmanin) and negative (DMSO) controls, and the IC50 values for PI3Kα, β, δ, and γ were calculated from the fit of the dose-response curves to a four-parameter equation. These assays generally produced results within 3-fold of the reported mean.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 519.97, ALogP 2.07, HBA 10, HBD 3, PSA 126.88, QED 0.35
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(C(F)(F)F)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MRHQRDLYXUJURF-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 554.62, ALogP 5.85, HBA 8, HBD 0, PSA 68.54, QED 0.26