lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOc1cc(N2CCC(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: UCTIQZALHPFVBB-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 765.89, ALogP 8.09, HBA 10, HBD 2, PSA 130.82, QED 0.13
Compound (SMILES): c1cc2c(ncn3nnc([C@H]4CC[C@H](CNc5ccc(N6CCOCC6)cc5)CC4)c23)[nH]1
InChIKey: MNJRACXEGYGQGZ-IYARVYRRSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 431.54, ALogP 3.83, HBA 7, HBD 2, PSA 83.37, QED 0.5
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3c(F)c(F)cc(F)c3F)CC2)C1
InChIKey: ATWNIMMKFHMANM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 538.51, ALogP 3.61, HBA 7, HBD 1, PSA 106.73, QED 0.31
Compound (SMILES): O[C@H]1CC[C@@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HPMRVSRZBKQEID-DTORHVGOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 257.3, ALogP 1.62, HBA 5, HBD 2, PSA 79.1, QED 0.69
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN2CCOCC2CO1
InChIKey: ZJFHLSCSEWIASA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 491.38, ALogP 4.17, HBA 8, HBD 1, PSA 77.97, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C3CCN(C(C)=O)CC3)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ACYBEMFGBZHIBB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 60.26 nM (pChEMBL 7.21999979019165)
Descriptors: MW 598.75, ALogP 3.81, HBA 10, HBD 0, PSA 92.09, QED 0.29
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(-c2ccc(O)c(C(N)=O)c2)cs1
InChIKey: VATKWVNDCITFEB-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
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 568.44, ALogP 6.2, HBA 9, HBD 3, PSA 132.48, QED 0.2
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cccc4ccccc34)CC2)C1
InChIKey: HHAUIQVPGMLYMC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 516.61, ALogP 4.2, HBA 7, HBD 1, PSA 106.73, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC[C@H]2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: CHNWMSQQHAFKHI-FSRHSHDFSA-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 472.59, ALogP 4.67, HBA 8, HBD 0, PSA 68.54, QED 0.37
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(CC#Cc2ccncc2)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: PWYSFHRYCZIJJM-LIJFRPJRSA-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 = 8128.31 nM (pChEMBL 5.090000152587891)
Descriptors: MW 504.59, ALogP 5.68, HBA 8, HBD 0, PSA 78.19, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(CCCN2C[C@@H](C)N[C@@H](C)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IJENXCZIMOXLKN-OYRHEFFESA-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 = 8128.31 nM (pChEMBL 5.090000152587891)
Descriptors: MW 515.66, ALogP 4.26, HBA 9, HBD 1, PSA 80.57, QED 0.35
Compound (SMILES): c1cc2c(ncn3nnc(C4CCN(C5CCCC5)CC4)c23)[nH]1
InChIKey: NRQQFRUCNQDBDE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 310.41, ALogP 2.73, HBA 5, HBD 1, PSA 62.11, QED 0.79
Compound (SMILES): CS(=O)(=O)c1ccc(CNC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: JYPQLENCUJFZLR-JCNLHEQBSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 438.56, ALogP 3.07, HBA 7, HBD 2, PSA 105.04, QED 0.48
Compound (SMILES): Cn1cc(-c2cc(CO)ccc2Oc2ccccc2)c2cc[nH]c2c1=O
InChIKey: SFDROCHFRBBUBF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: Compound dilution series were prepared in DMSO via an approximately 3-fold serial dilution. Compound dilutions were added directly into white, low-volume assay plates (Perkin Elmer Proxiplate 384 Plus#6008280) using a Labcyte Echo in conjunction with Labcyte Access and Thermo Multidrop CombinL robotics. Compounds were then suspended in eight microliters (μL) of assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and Alexa-647-conjugated probe.The final concentration of 1× assay mixture contained 2% DMSO, 12 nM His tagged BRD4 (BDI_K57-E168) and 100 nM probe or 4 nM His tagged BRD4 (BDII_E352-M457) and 30 nM probe, and 1 nM Europium-conjugated anti-His-tag antibody, and compound concentrations in the range of: 49.02 μM-0.61 nM or 0.98 μM-0.15 nM.After a one-hour equilibration at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 346.39, ALogP 3.82, HBA 4, HBD 2, PSA 67.25, QED 0.59
Compound (SMILES): COc1ccc(-c2ccc3ncnc(-c4cccc(C(=O)N5CCN(C(C)=O)CC5)c4)c3c2)cc1OC
InChIKey: NADSMCCUYCEYHM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3K-alpha (unknown origin) by KinaseGlo assay
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 496.57, ALogP 4.29, HBA 6, HBD 0, PSA 84.86, QED 0.41
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(C(F)(F)F)ncc3F)CC2)C1
InChIKey: JDKXQCYZSUBGIZ-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 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): Cc1ncccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: PEUAIYBHOLIJBN-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 496.58, ALogP 3.15, HBA 8, HBD 2, PSA 131.65, QED 0.43
Compound (SMILES): Cc1c(-c2c(Cl)cc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(F)cccn2c1=O
InChIKey: RXGHNLYVCPQUBS-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 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 571.01, ALogP 5.18, HBA 6, HBD 3, PSA 122.59, QED 0.27
Compound (SMILES): CC(=O)c1ccc(Nc2nccc3c(NC(=O)c4csc5c(N)ncnc45)c(C)ccc23)cc1
InChIKey: VDPIYNSZQSYYGQ-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Kinase Activity: The compounds prepared in Examples were tested for inhibitory activity against FMS, DDR1 and DDR2 kinases using Kinase Screening and Profiling Service (Invitrogen, U.S.).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 468.54, ALogP 5.33, HBA 8, HBD 3, PSA 122.89, QED 0.3
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)c(F)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: DCAGKJGCAXCDAL-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 762.84, ALogP 8.34, HBA 10, HBD 2, PSA 109.15, QED 0.14
Compound (SMILES): CC(C)(O)c1cn(-c2ccc(-c3cc(F)c(CO)c(S(C)(=O)=O)c3)cc2)c(C(C)(C)c2ccccc2Cl)n1
InChIKey: WUVSLEJBHNUDBB-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXR-beta in human whole blood assessed as ABCA1 gene induction by measuring ABCA1 mRNA level after 4 hrs by SYBR-Green dye-based Q-PCR analysis
Measurement: EC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 557.09, ALogP 5.78, HBA 6, HBD 2, PSA 92.42, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CCC(=O)O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: RETSMBIAYGNHLJ-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 433.47, ALogP 3.66, HBA 8, HBD 1, PSA 102.6, QED 0.45
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2c2ccncc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: UNSUYJXQOBXBNF-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 492.58, ALogP 5.38, HBA 8, HBD 0, PSA 78.19, QED 0.29
Compound (SMILES): CC[C@]1(C(=O)O)CC[C@H](C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC1
InChIKey: NMDBMKMFARAOPP-ATANMQQVSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Transactivation of human GAL4-fused LXRalpha expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 655.6, ALogP 6.69, HBA 4, HBD 1, PSA 91.75, QED 0.27
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3cccc(NS(=O)(=O)c4c(F)cccc4F)c3F)c2c1
InChIKey: XSFKXNZFVQQLSS-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 456.4, ALogP 3.88, HBA 5, HBD 2, PSA 115.71, QED 0.44
Compound (SMILES): CC#CC(=O)Nc1cc(-c2cnc3[nH]cc(Cl)c3c2)ccc1F
InChIKey: HBWIVNIJPLFQBT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Inhibition Assay: ITK and JAK3 Kinase assay procedures:Enzyme was incubated with substrate peptide in reaction buffer in the presence and absence of test compounds or Staurosporine. All additions were done on ice, followed by the addition of ATP mix. Wells were uniformly mixed using an Eppendorff plate shaker and incubated at 30° C. for 20 min, and stopped by the addition of 5 μL of 3% phosphoric acid. Volume was increased to 100 μL by adding 0.8% phosphoric acid which was then transferred to PC filter mats (Millipore), pre-equilibrated with 70% ethanol and water. Plates were washed thrice with 100 μL 0.8% phosphoric acid and dried for an hour at 60° C. 100 μL scintillation fluid was added into each well and reading taken in Perkin Elmer TOPCOUNT beta counter. The data analysis was performed by averaging the duplicate top count readings for each standard, negative, positive control (enzyme control) and samples and subtracting the average negative control from each reading which results in corrected values.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 327.75, ALogP 3.98, HBA 2, HBD 2, PSA 57.78, QED 0.7
Compound (SMILES): CCN(CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)C(C)C.Cl
InChIKey: VISMWVZBCCXDPW-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 474.61, ALogP 4.92, HBA 8, HBD 0, PSA 68.54, QED 0.32
Compound (SMILES): Cn1cc(Nc2ncc(Cl)c(NC3CCC4(CC3)CCN(C(=O)CC#N)C4)n2)cn1
InChIKey: OYVOATNFWDYRPN-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Kinase Assay: TYK2 (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 250 μM GGMEDIYFEFMGGKKK, 10 mM MgAcetate and [γ-33P-ATP](specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 μL of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 428.93, ALogP 3.09, HBA 8, HBD 2, PSA 111.76, QED 0.75
Compound (SMILES): COC(=O)N[C@@H](C(=O)N1CCC[C@@H]1c1ncc(-c2ccc3cc(-c4ccc5nc([C@H]6CCCN6C(=O)[C@H](NC(=O)OC)[C@H](C)OC)[nH]c5c4)ccc3c2)[nH]1)C(C)C
InChIKey: QCDPCGCVNMYPHK-PWVNGPOOSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Transient Transfection Assay: In a transient set-up, a Huh-7 lunet hepatoma cell line was transiently transfected with an autonomously replicating RNA encoding a bi-cistronic expression construct. This construct comprises a firefly luciferase reporter gene preceding the NS3-NS5B subgenomic region of HCV (genotype 1a H77 or 1b Con1). Translation of the HCV subgenomic region is mediated by an internal ribosome entry site of encephalomyocarditis virus. The construct is furthermore flanked by 5' and 3' untranslated regions of HCV (genotype 1a H77 or 1b Con 1, respectively), which allow for replication of the RNA. In addition to the wild-type constructs, site-directed mutations were introduced into the transient HCV genotype 1b replicon in the gene encoding for the non-structural protein 5A (NS5A). More precisely, amino acid residues 28, 30, 31 and 93 in NS5A were independently altered. Cells were plated in 384 well plates in the presence of test and control compounds, which were added in various concentrations. Following an incubation of two days, replication of the HCV subgenomic replicon RNA was measured by assaying luciferase activity (using standard luciferase assay substrates and reagents and a Perkin Elmer ViewLux™ ultraHTS microplate imager).
Measurement: EC50 = 0.042 nM (pChEMBL 10.380000114440918)
Descriptors: MW 778.91, ALogP 6.24, HBA 9, HBD 4, PSA 183.87, QED 0.12
Compound (SMILES): Cc1nc(C(F)(F)F)ccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: YPWWOTZOZAXQKM-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 564.58, ALogP 4.16, HBA 8, HBD 2, PSA 131.65, QED 0.37
Compound (SMILES): CNC(=O)c1cc(F)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CAMOGMXHVRSGKE-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 420.45, ALogP 2.66, HBA 7, HBD 2, PSA 96.17, QED 0.5
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3c(F)cccn23)n1
InChIKey: UZNKAXPRQVARSF-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 732.81, ALogP 8.33, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nnc(-c2ccc(C)cc2)o1
InChIKey: ZNOFYQJDWNDHAI-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
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 508.37, ALogP 6.63, HBA 8, HBD 1, PSA 95.19, QED 0.26
Compound (SMILES): COc1ccc2nc(NC3=NC[C@@]4(CN5CCC4CC5)O3)sc2c1
InChIKey: KIDXXFXVPLATJJ-KRWDZBQOSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Agonist activity at rat alpha3beta4 nAChR expressed in HEK293 cells for 2 mins by FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 344.44, ALogP 2.57, HBA 7, HBD 1, PSA 58.98, QED 0.91
Compound (SMILES): CC1=CC(=O)C(C(C)C)=C/C1=N/OC(=O)c1ccccc1C
InChIKey: CMOJHDQJJPIVEC-MNDPQUGUSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Binding affinity to GST-tagged PLK1 PBD (327 to 603 residues) (unknown origin) by NT-647 dye-based microscale thermophoresis analysis
Measurement: Kd = 35700 nM (pChEMBL 4.449999809265137)
Descriptors: MW 297.35, ALogP 3.62, HBA 4, HBD 0, PSA 55.73, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(CCNCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DYLLHXRSSYZCKB-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 448.53, ALogP 2.77, HBA 9, HBD 2, PSA 97.56, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN2C(=O)c3ccccc3C2=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FQDRWRLLOXGGSS-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 534.58, ALogP 4.48, HBA 9, HBD 0, PSA 102.68, QED 0.27
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(CN4CCC4)nc(C(F)(F)F)n3)CC2)C1
InChIKey: MWGJEAKQQFZRHH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 605.63, ALogP 3.07, HBA 10, HBD 1, PSA 135.75, QED 0.34
Compound (SMILES): COc1ccc(Cl)c(N(CCO)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: HGAFTPHVPFQPHO-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 395.85, ALogP 3.81, HBA 6, HBD 2, PSA 87.16, QED 0.52
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(N2CCNCC2)n1
InChIKey: RGUFKCMSOMSTHM-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
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 517.44, ALogP 5.13, HBA 9, HBD 2, PSA 84.43, QED 0.35
Compound (SMILES): c1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: GCJYVBVRNNJNAU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 332.41, ALogP 2.99, HBA 5, HBD 1, PSA 62.11, QED 0.63
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HLPZBUCKWKGYBH-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 544.54, ALogP 5.65, HBA 8, HBD 0, PSA 78.19, QED 0.26
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(-c4cccc(C#N)c4)c(F)c3)CC2)C1
InChIKey: FYATUSPSVPIDFE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 585.65, ALogP 4.73, HBA 8, HBD 1, PSA 130.52, QED 0.3
Compound (SMILES): CCOc1cc(N2CCN(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: QZWUFSOCTRROPU-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 766.87, ALogP 6.61, HBA 11, HBD 2, PSA 134.06, QED 0.14
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(O)c(F)cc12
InChIKey: HMMXUGABDMMBFW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 318.35, ALogP 2.66, HBA 4, HBD 2, PSA 65.56, QED 0.85
Compound (SMILES): COCC(O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: IVVNCQGZOKJKEC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.715 nM (pChEMBL 8.430000305175781)
Descriptors: MW 449.51, ALogP 3.19, HBA 9, HBD 1, PSA 94.76, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)CNC(C)C)c1
InChIKey: DVBMTJCMGPJACG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.413 nM (pChEMBL 8.850000381469727)
Descriptors: MW 460.58, ALogP 4.57, HBA 8, HBD 1, PSA 77.33, QED 0.39
Compound (SMILES): CCC(=O)N1CCN(S(=O)(=O)c2cccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)c2)CC1
InChIKey: NIWBUWMZKOEJTN-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora kinase B (D25 to A303 residues) expressed in mammalian expression system by Z'LYTE assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 549.66, ALogP 3.13, HBA 8, HBD 1, PSA 119.05, QED 0.52
Compound (SMILES): COc1ccc2ccc(S(=O)(=O)N[C@H]3CCN(Cc4ccc5nc(N)[nH]c5c4)C3=O)cc2c1
InChIKey: BTOKMAIVSPYLMD-FQEVSTJZSA-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 = 3550 nM (pChEMBL 5.449999809265137)
Descriptors: MW 465.54, ALogP 2.39, HBA 6, HBD 3, PSA 130.41, QED 0.4
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(CN2CCOCC2)cs1
InChIKey: FTIMKXNADWOPKE-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 532.45, ALogP 5.56, HBA 9, HBD 1, PSA 81.63, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CCS(C)(=O)=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VITKBUDPMVQPFZ-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 = 5.248 nM (pChEMBL 8.279999732971191)
Descriptors: MW 467.55, ALogP 3.23, HBA 9, HBD 0, PSA 99.44, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC[C@@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LKMLECIRYJPQOC-JOCHJYFZSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged VEGFR2 (790 end residues) expressed in baculovirus infected insect Sf21 cells using Btn-Flt3 as substrate after 1 hr by time resolved fluorescence assay
Measurement: IC50 = 33.88 nM (pChEMBL 7.46999979019165)
Descriptors: MW 502.62, ALogP 4.03, HBA 9, HBD 1, PSA 88.77, QED 0.35
Compound (SMILES): COc1cc(F)cc(N(CCCN2CCC(C#N)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NSRRVSVPEXCSGE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.761 nM (pChEMBL 8.170000076293945)
Descriptors: MW 485.57, ALogP 4.55, HBA 8, HBD 0, PSA 83.1, QED 0.36
Compound (SMILES): COc1ncc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(NS(=O)(=O)c5cccc(F)c5)c4F)c3c2)cn1
InChIKey: ZAZVIZDQSOFUFL-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 539.5, ALogP 4.48, HBA 7, HBD 2, PSA 126.93, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCCC2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: VVXGTLFJZWGABM-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 = 1.23 nM (pChEMBL 8.90999984741211)
Descriptors: MW 486.62, ALogP 5.06, HBA 8, HBD 0, PSA 68.54, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC2=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KJZWLNUAUHEQCJ-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 = 33.11 nM (pChEMBL 7.480000019073486)
Descriptors: MW 472.55, ALogP 3.81, HBA 8, HBD 0, PSA 85.61, QED 0.39
Compound (SMILES): Nc1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc(N)cc5)ccc4o3)cc2)cc1
InChIKey: LCYYWRRGEZMPJO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 41000 nM (pChEMBL 4.389999866485596)
Descriptors: MW 535.61, ALogP 4.26, HBA 8, HBD 4, PSA 170.41, QED 0.22
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DDNOUEXAVDQPMR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 435.48, ALogP 2.54, HBA 9, HBD 2, PSA 105.76, QED 0.44
Compound (SMILES): Cc1cccc(-c2c[nH]c3ncc(-c4cccc(NC(=O)/C=C/CN(C)C)c4)cc23)c1F
InChIKey: PRIQLBRXOCMBJB-IZZDOVSWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Inhibition Assay: ITK and JAK3 Kinase assay procedures:Enzyme was incubated with substrate peptide in reaction buffer in the presence and absence of test compounds or Staurosporine. All additions were done on ice, followed by the addition of ATP mix. Wells were uniformly mixed using an Eppendorff plate shaker and incubated at 30° C. for 20 min, and stopped by the addition of 5 μL of 3% phosphoric acid. Volume was increased to 100 μL by adding 0.8% phosphoric acid which was then transferred to PC filter mats (Millipore), pre-equilibrated with 70% ethanol and water. Plates were washed thrice with 100 μL 0.8% phosphoric acid and dried for an hour at 60° C. 100 μL scintillation fluid was added into each well and reading taken in Perkin Elmer TOPCOUNT beta counter. The data analysis was performed by averaging the duplicate top count readings for each standard, negative, positive control (enzyme control) and samples and subtracting the average negative control from each reading which results in corrected values.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 428.51, ALogP 5.4, HBA 3, HBD 2, PSA 61.02, QED 0.4
Compound (SMILES): O[C@H]1CC[C@@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HPMRVSRZBKQEID-DTORHVGOSA-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 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 257.3, ALogP 1.62, HBA 5, HBD 2, PSA 79.1, QED 0.69
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN2CCOCC2CO1
InChIKey: ZJFHLSCSEWIASA-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
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 491.38, ALogP 4.17, HBA 8, HBD 1, PSA 77.97, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C3CCN(C(C)=O)CC3)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ACYBEMFGBZHIBB-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 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 598.75, ALogP 3.81, HBA 10, HBD 0, PSA 92.09, QED 0.29
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(-c2ccc(O)c(C(N)=O)c2)cs1
InChIKey: VATKWVNDCITFEB-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 568.44, ALogP 6.2, HBA 9, HBD 3, PSA 132.48, QED 0.2