lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1c2ncn(-c3ncccc3F)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: UGDRWAKRKFUNEE-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
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 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 438.81, ALogP 4.84, HBA 4, HBD 0, PSA 51.02, QED 0.54
Compound (SMILES): CCCSc1nc2c(c(=O)n1-c1ccccc1OC)SCC2
InChIKey: MXDVDZKXHJWBLR-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 334.47, ALogP 3.39, HBA 6, HBD 0, PSA 44.12, QED 0.62
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(-c4ccc5ncccc5c4)c(F)c3)CC2)C1
InChIKey: WZAHZXZSJCINDG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 611.69, ALogP 5.41, HBA 8, HBD 1, PSA 119.62, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)[C@H]2CC[C@@H](NC(C)C)CC2)c1
InChIKey: AHSYHYFTUKZLCI-SZPZYZBQSA-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 500.65, ALogP 5.49, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC(O)C(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: JXGGHGLZZYBWNG-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 = 2.754 nM (pChEMBL 8.5600004196167)
Descriptors: MW 501.51, ALogP 5.15, HBA 8, HBD 1, PSA 85.53, QED 0.36
Compound (SMILES): Cc1c(C(=O)N2Cc3nnn(-c4ncc(F)cn4)c3C[C@@H]2C)cccc1C(F)(F)F
InChIKey: ABRKNOBDRPPGRG-JTQLQIEISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-Mephenytoin as substrate
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 420.37, ALogP 3.11, HBA 6, HBD 0, PSA 76.8, QED 0.6
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(F)cc3C(F)(F)F)CC2)C1
InChIKey: RZUCZMLSGAQMJN-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 567.55, ALogP 4.6, HBA 7, HBD 2, PSA 118.76, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1.Cl
InChIKey: VNKOQGCHLFSNGI-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 = 10.23 nM (pChEMBL 7.989999771118164)
Descriptors: MW 528.58, ALogP 5.77, HBA 8, HBD 1, PSA 77.33, QED 0.25
Compound (SMILES): COc1cc(OC)cc(N(CCCn2c(C)cnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: DULJZQNTEOXLFX-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 nM (pChEMBL 8)
Descriptors: MW 497.6, ALogP 5.09, HBA 9, HBD 0, PSA 83.12, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCn2c(C)cnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MUFKFZHTITXUCK-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 = 66.07 nM (pChEMBL 7.179999828338623)
Descriptors: MW 483.58, ALogP 4.7, HBA 9, HBD 0, PSA 83.12, QED 0.32
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2=O)cc1)c1cc(CO)n(Cc2cc(-c3ccc(Cl)s3)on2)n1
InChIKey: FQRGFMDCLSIWKO-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 = 1.39 nM (pChEMBL 8.859999656677246)
Descriptors: MW 513.96, ALogP 3.41, HBA 9, HBD 2, PSA 122.72, QED 0.39
Compound (SMILES): FC(F)(F)Sc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: SFYDGMHYRUGYLJ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 432.48, ALogP 4.6, HBA 6, HBD 1, PSA 62.11, QED 0.48
Compound (SMILES): COc1cc(OC)cc(N(CCCc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KSWZVURHYKWKHC-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 = 26.3 nM (pChEMBL 7.579999923706055)
Descriptors: MW 510.6, ALogP 5.22, HBA 9, HBD 0, PSA 87.42, QED 0.25
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NTSVKEPNLGDQBL-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 = 5.623 nM (pChEMBL 8.25)
Descriptors: MW 473.58, ALogP 3.53, HBA 8, HBD 2, PSA 97.2, QED 0.38
Compound (SMILES): Cc1nn(C)c(C)c1N(C)S(=O)(=O)c1c(Cl)cc(CCCN2CCNCC2)cc1Cl
InChIKey: YMLFRSAHQNBEFS-UHFFFAOYSA-N
Target: Glycylpeptide N-tetradecanoyltransferase (SINGLE PROTEIN), Leishmania major
UniProt: Q4Q5S8
Assay: Inhibition of Leishmania major NMT L421Q mutant expressed in Escherichia coli Rosetta-2 cells using GSNKSKPK as substrate in presence of MyrCoA after 30 mins by CPM dye based fluorescence assay
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 474.46, ALogP 3.01, HBA 6, HBD 1, PSA 70.47, QED 0.67
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(Cl)nc4)cc23)c1F
InChIKey: OIBJFKDNKMXSGB-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 490.92, ALogP 4.94, HBA 5, HBD 2, PSA 104.81, QED 0.28
Compound (SMILES): Cn1c(=O)n(-c2cccc(-c3c(F)cc(C(N)=O)c4[nH]c5cc(C(C)(C)O)ccc5c34)c2Cl)c(=O)c2cccc(F)c21
InChIKey: CACKWDPMBIYJAG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 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.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 589, ALogP 5.25, HBA 6, HBD 3, PSA 123.11, QED 0.26
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QKNXNIJTPNITNW-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 = 77.62 nM (pChEMBL 7.110000133514404)
Descriptors: MW 539.68, ALogP 4.9, HBA 8, HBD 0, PSA 79.62, QED 0.3
Compound (SMILES): Clc1ncc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)s1
InChIKey: XUZXYEBCRSNLCA-UHFFFAOYSA-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 373.87, ALogP 3.1, HBA 7, HBD 1, PSA 75, QED 0.6
Compound (SMILES): CCS(=O)(=O)NCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: SQEZUHWWJYSRDG-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 = 0.871 nM (pChEMBL 9.0600004196167)
Descriptors: MW 496.59, ALogP 3.12, HBA 9, HBD 1, PSA 111.47, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: FIPKJBQQLVYHGW-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 = 54.95 nM (pChEMBL 7.260000228881836)
Descriptors: MW 457.58, ALogP 5.71, HBA 7, HBD 0, PSA 65.3, QED 0.32
Compound (SMILES): Cc1ccc(C2=C(c3nnn[nH]3)C(=O)N[C@@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)C2)cc1
InChIKey: AEMPUAWUDAMJBV-QFIPXVFZSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: Inhibition of human MGAT2 in mouse STC-1 cell based assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 525.45, ALogP 5.12, HBA 5, HBD 2, PSA 92.79, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCCc2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KDMGWBBETGCJDN-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 = 28.18 nM (pChEMBL 7.550000190734863)
Descriptors: MW 511.59, ALogP 4.62, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): CC(=O)NC1CCC(c2nnc(SCCCN3CC[C@]4(C[C@@H]4c4ccc(C(F)(F)F)cc4)C3)n2C)CC1
InChIKey: QDBPUGDJXGIOJW-HFYIJGDASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes coexpressing Galpha16 after 120 mins by liquid scintillation counting
Measurement: Ki = 457.09 nM (pChEMBL 6.340000152587891)
Descriptors: MW 535.68, ALogP 5.36, HBA 6, HBD 1, PSA 63.05, QED 0.36
Compound (SMILES): COc1cccc(F)c1CN1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: CUOPRISSKJCUKG-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 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 500.58, ALogP 3.56, HBA 8, HBD 1, PSA 98.89, QED 0.41
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NKVDPZYKPGKBTK-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 = 2.344 nM (pChEMBL 8.630000114440918)
Descriptors: MW 500.48, ALogP 3.86, HBA 8, HBD 1, PSA 94.4, QED 0.39
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)cc2)cc(OC)c1
InChIKey: GCPFDXOLQNQCTI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 362.45, ALogP 3.14, HBA 5, HBD 2, PSA 76.66, QED 0.75
Compound (SMILES): c1ccc(CCCN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: OAAWZOIHZUDJRD-UHFFFAOYSA-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. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 360.47, ALogP 3.42, HBA 5, HBD 1, PSA 62.11, QED 0.59
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: INWHLZUNIJSPHA-JOCHJYFZSA-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 = 1.175 nM (pChEMBL 8.930000305175781)
Descriptors: MW 473.46, ALogP 4.11, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COc1cc(N2Cc3cn(-c4cccc(S(C)(=O)=O)c4)nc3[C@H]2C(C)C)ccn1
InChIKey: LYZQPKJAYGTLJX-OAQYLSRUSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 5625 nM (pChEMBL 5.25)
Descriptors: MW 412.52, ALogP 3.4, HBA 7, HBD 0, PSA 77.32, QED 0.64
Compound (SMILES): CC1=C(N2CCC3(CCN(C[C@H](O)c4ccc5c(c4C)COC5=O)CC3)C2=O)COC1=O
InChIKey: KDAIMYGCILCZSH-FQEVSTJZSA-N
Target: Inward rectifier potassium channel 13 (SINGLE PROTEIN), Homo sapiens
UniProt: O60928
Assay: Inhibition of Kir7.1 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 440.5, ALogP 1.84, HBA 7, HBD 1, PSA 96.38, QED 0.71
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C5CCOCC5)c4)nc3c2)c1
InChIKey: OXOGSNQFCPKZMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 516.65, ALogP 5, HBA 9, HBD 1, PSA 86.56, QED 0.32
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: MNAFRWGRFIBAQX-AVRDEDQJSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in microsomes using ER as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 477.56, ALogP 5.16, HBA 7, HBD 0, PSA 59.98, QED 0.35
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnn(Cc5ccccc5)c4)cc23)c1F
InChIKey: YWNLVLUPBGVIJZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 535.58, ALogP 5.14, HBA 6, HBD 2, PSA 109.74, QED 0.25
Compound (SMILES): CC(C)(O)CNc1ncc(-c2ccnc(Nc3ccnc(Cl)c3)n2)c(CC2CC2)n1
InChIKey: AWNXKZVIZARMME-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: O60331
Assay: Selectivity interaction (Lipid kinase panel (AstraZeneca)) EUB0000631a PIP5K1C
Measurement: IC50 = 382 nM (pChEMBL 6.420000076293945)
Descriptors: MW 425.92, ALogP 3.86, HBA 8, HBD 3, PSA 108.74, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(CCC#N)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: LBGCXBADNLLJIM-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 = 1.549 nM (pChEMBL 8.8100004196167)
Descriptors: MW 444.5, ALogP 3.55, HBA 9, HBD 1, PSA 109.32, QED 0.42
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCNC(=O)C1
InChIKey: ARSLLTCMIOZESX-PNYWAOBFSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in microsomes using BMC as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 21000 nM (pChEMBL 4.677999973297119)
Descriptors: MW 493.6, ALogP 4.19, HBA 6, HBD 1, PSA 63.05, QED 0.46
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(CN2CCN(C)CC2)cs1
InChIKey: AYWUHPUXKGVOSD-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 545.5, ALogP 5.47, HBA 9, HBD 1, PSA 75.64, QED 0.31
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(F)cc4)ccc3o2)cc1)c1ccc(F)cc1
InChIKey: LRFLFBGHSCCUCH-UHFFFAOYSA-N
Target: Phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: A0A045ISB3
Assay: Inhibition of Mycobacterium tuberculosis His-tagged PtpB expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 30 mins by spectrophotometric method
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 541.56, ALogP 5.37, HBA 6, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): Cc1cc(C)c(CC(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c(C)c1
InChIKey: XZRZKPSBFSPKKR-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 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 522.66, ALogP 3.9, HBA 7, HBD 1, PSA 106.73, QED 0.41
Compound (SMILES): C[C@@H]1CN(Cc2ccccc2)c2ccccc2[C@H](C)N1C(=O)NCc1ccccc1
InChIKey: JFGVQJFBQJWZAW-RTWAWAEBSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1I (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0X4
Assay: Inhibition of Cav3.3 subunit 1alpha-l(unknown origin) stably transfected in HEK293 cells measured by FLIPR assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 399.54, ALogP 5.37, HBA 2, HBD 1, PSA 35.58, QED 0.64
Compound (SMILES): CCCSc1nc2c(c(=O)n1-c1ccccc1OC)SCC2
InChIKey: MXDVDZKXHJWBLR-UHFFFAOYSA-N
Target: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P51160
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 334.47, ALogP 3.39, HBA 6, HBD 0, PSA 44.12, QED 0.62
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)[C@H]2CC[C@@H](NC(C)C)CC2)c1
InChIKey: AHSYHYFTUKZLCI-SZPZYZBQSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 500.65, ALogP 5.49, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC(O)C(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: JXGGHGLZZYBWNG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.818 nM (pChEMBL 8.550000190734863)
Descriptors: MW 501.51, ALogP 5.15, HBA 8, HBD 1, PSA 85.53, QED 0.36
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(F)cc3C(F)(F)F)CC2)C1
InChIKey: RZUCZMLSGAQMJN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) 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 μL 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 hour 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 PHERA star plate reader (BMG, Cary, N.C.). The data for the JAK1 and/or JAK2 inhibitors were obtained by testing the compounds in the Example A assay at 1 mM ATP.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 567.55, ALogP 4.6, HBA 7, HBD 2, PSA 118.76, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1.Cl
InChIKey: VNKOQGCHLFSNGI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 528.58, ALogP 5.77, HBA 8, HBD 1, PSA 77.33, QED 0.25
Compound (SMILES): COc1cc(OC)cc(N(CCCn2c(C)cnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: DULJZQNTEOXLFX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.467 nM (pChEMBL 8.350000381469727)
Descriptors: MW 497.6, ALogP 5.09, HBA 9, HBD 0, PSA 83.12, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCn2c(C)cnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MUFKFZHTITXUCK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 58.88 nM (pChEMBL 7.230000019073486)
Descriptors: MW 483.58, ALogP 4.7, HBA 9, HBD 0, PSA 83.12, QED 0.32
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2=O)cc1)c1cc(CO)n(Cc2cc(-c3ccc(Cl)s3)on2)n1
InChIKey: FQRGFMDCLSIWKO-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 60 min reaction time after substrate addition.
Measurement: IC50 = 1.58 nM (pChEMBL 8.800000190734863)
Descriptors: MW 513.96, ALogP 3.41, HBA 9, HBD 2, PSA 122.72, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(CCCc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KSWZVURHYKWKHC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 33.88 nM (pChEMBL 7.46999979019165)
Descriptors: MW 510.6, ALogP 5.22, HBA 9, HBD 0, PSA 87.42, QED 0.25
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NTSVKEPNLGDQBL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.918 nM (pChEMBL 8.15999984741211)
Descriptors: MW 473.58, ALogP 3.53, HBA 8, HBD 2, PSA 97.2, QED 0.38
Compound (SMILES): Cc1nn(C)c(C)c1N(C)S(=O)(=O)c1c(Cl)cc(CCCN2CCNCC2)cc1Cl
InChIKey: YMLFRSAHQNBEFS-UHFFFAOYSA-N
Target: Glycylpeptide N-tetradecanoyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30419
Assay: Inhibition of human NMT1 L495M mutant expressed in Escherichia coli Rosetta-2 cells using GSNKSKPK as substrate in presence of MyrCoA after 30 mins by CPM dye based fluorescence assay
Measurement: Ki = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 474.46, ALogP 3.01, HBA 6, HBD 1, PSA 70.47, QED 0.67
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(Cl)nc4)cc23)c1F
InChIKey: OIBJFKDNKMXSGB-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 490.92, ALogP 4.94, HBA 5, HBD 2, PSA 104.81, QED 0.28
Compound (SMILES): Cn1c(=O)n(-c2cccc(-c3c(F)cc(C(N)=O)c4[nH]c5cc(C(C)(C)O)ccc5c34)c2Cl)c(=O)c2cccc(F)c21
InChIKey: CACKWDPMBIYJAG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 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.
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 589, ALogP 5.25, HBA 6, HBD 3, PSA 123.11, QED 0.26
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QKNXNIJTPNITNW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 81.28 nM (pChEMBL 7.090000152587891)
Descriptors: MW 539.68, ALogP 4.9, HBA 8, HBD 0, PSA 79.62, QED 0.3
Compound (SMILES): CCS(=O)(=O)NCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: SQEZUHWWJYSRDG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.445 nM (pChEMBL 8.84000015258789)
Descriptors: MW 496.59, ALogP 3.12, HBA 9, HBD 1, PSA 111.47, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: FIPKJBQQLVYHGW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 64.57 nM (pChEMBL 7.190000057220459)
Descriptors: MW 457.58, ALogP 5.71, HBA 7, HBD 0, PSA 65.3, QED 0.32
Compound (SMILES): Cc1ccc(C2=C(c3nnn[nH]3)C(=O)N[C@@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)C2)cc1
InChIKey: AEMPUAWUDAMJBV-QFIPXVFZSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q921V5
Assay: Inhibition of mouse MGAT2 in mouse STC-1 cell based assay
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 525.45, ALogP 5.12, HBA 5, HBD 2, PSA 92.79, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCCc2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KDMGWBBETGCJDN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 20.42 nM (pChEMBL 7.690000057220459)
Descriptors: MW 511.59, ALogP 4.62, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): CC(=O)NC1CCC(c2nnc(SCCCN3CC[C@]4(C[C@@H]4c4ccc(C(F)(F)F)cc4)C3)n2C)CC1
InChIKey: QDBPUGDJXGIOJW-HFYIJGDASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG transfected in HEK293 cells assessed as reduction in tail current by patch clamp assay
Measurement: IC50 = 6918.31 nM (pChEMBL 5.159999847412109)
Descriptors: MW 535.68, ALogP 5.36, HBA 6, HBD 1, PSA 63.05, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NKVDPZYKPGKBTK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.57 nM (pChEMBL 8.59000015258789)
Descriptors: MW 500.48, ALogP 3.86, HBA 8, HBD 1, PSA 94.4, QED 0.39
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)cc2)cc(OC)c1
InChIKey: GCPFDXOLQNQCTI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 362.45, ALogP 3.14, HBA 5, HBD 2, PSA 76.66, QED 0.75
Compound (SMILES): c1ccc(CCCN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: OAAWZOIHZUDJRD-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 360.47, ALogP 3.42, HBA 5, HBD 1, PSA 62.11, QED 0.59
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: INWHLZUNIJSPHA-JOCHJYFZSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 473.46, ALogP 4.11, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): CC1=C(N2CCC3(CCN(C[C@H](O)c4ccc5c(c4C)COC5=O)CC3)C2=O)COC1=O
InChIKey: KDAIMYGCILCZSH-FQEVSTJZSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 440.5, ALogP 1.84, HBA 7, HBD 1, PSA 96.38, QED 0.71
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C5CCOCC5)c4)nc3c2)c1
InChIKey: OXOGSNQFCPKZMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 516.65, ALogP 5, HBA 9, HBD 1, PSA 86.56, QED 0.32
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@H]3c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: MNAFRWGRFIBAQX-AVRDEDQJSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes coexpressing Galpha16 after 120 mins by liquid scintillation counting
Measurement: Ki = 660.69 nM (pChEMBL 6.179999828338623)
Descriptors: MW 477.56, ALogP 5.16, HBA 7, HBD 0, PSA 59.98, QED 0.35
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnn(Cc5ccccc5)c4)cc23)c1F
InChIKey: YWNLVLUPBGVIJZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 535.58, ALogP 5.14, HBA 6, HBD 2, PSA 109.74, QED 0.25
Compound (SMILES): CC(C)(O)CNc1ncc(-c2ccnc(Nc3ccnc(Cl)c3)n2)c(CC2CC2)n1
InChIKey: AWNXKZVIZARMME-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: O60331
Assay: Selectivity interaction (Lipid kinase panel (ProQuinase)) EUB0000631a PIP5K1C
Measurement: IC50 = 3370 nM (pChEMBL 5.46999979019165)
Descriptors: MW 425.92, ALogP 3.86, HBA 8, HBD 3, PSA 108.74, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(CCC#N)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: LBGCXBADNLLJIM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.344 nM (pChEMBL 8.630000114440918)
Descriptors: MW 444.5, ALogP 3.55, HBA 9, HBD 1, PSA 109.32, QED 0.42
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCNC(=O)C1
InChIKey: ARSLLTCMIOZESX-PNYWAOBFSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in microsomes using MMC as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 21000 nM (pChEMBL 4.677999973297119)
Descriptors: MW 493.6, ALogP 4.19, HBA 6, HBD 1, PSA 63.05, QED 0.46
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(CN2CCN(C)CC2)cs1
InChIKey: AYWUHPUXKGVOSD-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 545.5, ALogP 5.47, HBA 9, HBD 1, PSA 75.64, QED 0.31
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(F)cc4)ccc3o2)cc1)c1ccc(F)cc1
InChIKey: LRFLFBGHSCCUCH-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTPN1 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 541.56, ALogP 5.37, HBA 6, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): CCCSc1nc2c(c(=O)n1-c1ccccc1OC)SCC2
InChIKey: MXDVDZKXHJWBLR-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 334.47, ALogP 3.39, HBA 6, HBD 0, PSA 44.12, QED 0.62
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)[C@H]2CC[C@@H](NC(C)C)CC2)c1
InChIKey: AHSYHYFTUKZLCI-SZPZYZBQSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.09 nM (pChEMBL 8.510000228881836)
Descriptors: MW 500.65, ALogP 5.49, HBA 8, HBD 1, PSA 77.33, QED 0.34