lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1C[C@H]2CSC(N)=N[C@@]2(c2nc(NC(=O)c3ccc(F)cn3)cs2)CO1
InChIKey: QQBRRRLRJBDPNK-YMNVWFMLSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: BACE1 Cell-Free Assay: The substrate is Biotin-GLTNIKTEEISEISY^EVEFR-C[Oregon Green]KK-OH. The BACE1 enzyme is affinity purified material from conditioned media of CHO-K1 cells that have been transfected with a soluble BACE construct (BACE1deltaTM96His). Compounds are incubated in a ½ log dose response curve from a top concentration of 100 μM with BACE1 enzyme and the biotinylated fluorescent peptide in 384-well black plates (Thermo Scientific #4318). BACE1 is at a final concentration of 0.1 nM with a final concentration of peptide substrate of 150 nM in a reaction volume of 30 μL assay buffer [100 mM sodium acetate, pH 4.5 (brought to pH with acetic acid), and 0.001% Tween-20]. Plates are covered and incubated for 3 hours at 37 °C. The reaction is stopped with the addition of 30 μL of 1.5 μM Streptavidin (Pierce, #21125). After a 10 minute incubation at room temperature, plates are read on a PerkinElmer EnVision for fluorescence polarization (Ex485 nm/Em530 nm).
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 407.5, ALogP 2.61, HBA 8, HBD 2, PSA 102.49, QED 0.81
Compound (SMILES): CS(=O)(=O)CCN1CCN(C2CCN(c3ccc(Nc4nccc(-c5c(-c6cccc(C(=O)Nc7c(F)cccc7F)c6)nc6ccccn56)n4)c(OCC(F)(F)F)c3)CC2)CC1
InChIKey: VDXNZNRAXNGSEG-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 889.95, ALogP 7.3, HBA 12, HBD 2, PSA 137.3, QED 0.11
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(Cl)c(F)cc12
InChIKey: UDSAMCMJMDTOJQ-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 336.79, ALogP 3.6, HBA 3, HBD 1, PSA 45.33, QED 0.87
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H]2CCCN2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SYQCXJZLWMRWKD-SFHVURJKSA-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 444.54, ALogP 3.94, HBA 8, HBD 1, PSA 77.33, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC(C)N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AHWOGVXLWKIELS-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 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)CN)c1
InChIKey: SOYCCBHGJYSWNQ-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 = 1.349 nM (pChEMBL 8.869999885559082)
Descriptors: MW 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(-c2ccccn2)cs1
InChIKey: JFLJVHMCZLMBSN-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 510.41, ALogP 6.79, HBA 8, HBD 1, PSA 82.05, QED 0.26
Compound (SMILES): CSc1ccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NS(=O)(=O)C2CC2)cc1
InChIKey: NGLPZZZUWGVILU-QLXKLKPCSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to ERbeta (unknown origin) by FP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.64, ALogP 5.48, HBA 6, HBD 1, PSA 73.22, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C5CCN(C(=O)OC(C)(C)C)CC5)c4)nc3c2)c1
InChIKey: SRQIALHPCHADMP-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 = 3.09 nM (pChEMBL 8.510000228881836)
Descriptors: MW 574.68, ALogP 5.21, HBA 10, HBD 1, PSA 115.07, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCCCN2)n1
InChIKey: FZGGLLMOLZVRHY-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 516.45, ALogP 6.54, HBA 8, HBD 2, PSA 81.19, QED 0.29
Compound (SMILES): COc1ncc(-c2ccc3ncnc(-c4cccc(C(=O)N5CCN(C(C)=O)CC5)c4)c3c2)cc1C#N
InChIKey: QYTXJLQBSYAMGR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Mus musculus
UniProt: O35904
Assay: Inhibition of PI3Kdelta in Balb/c mouse in rat B cells assessed as reduction in anti-IgM induced proliferation measured over last 16 hrs of 88 hrs by [3H]-Thymidine incorporation assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 492.54, ALogP 3.54, HBA 7, HBD 0, PSA 112.31, QED 0.43
Compound (SMILES): CCC(=O)N1CC[C@H](Oc2ccnc3ccc(-c4ccc(OC)nc4)nc23)C1
InChIKey: BXJYFFUVJNTZJH-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of myristoylated PI3K-beta (unknown origin) overexpressed in Rat1 cells assessed as inhibition of Akt phosphorylation
Measurement: IC50 = 3210 nM (pChEMBL 5.489999771118164)
Descriptors: MW 378.43, ALogP 3.09, HBA 6, HBD 0, PSA 77.44, QED 0.68
Compound (SMILES): CCN1CCN(c2noc(COc3cc4ncnc(Nc5ccc(Cl)c(Cl)c5)c4cc3OC)n2)CC1
InChIKey: FGHXOSBHGQKMBX-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 530.42, ALogP 4.79, HBA 10, HBD 1, PSA 101.67, QED 0.34
Compound (SMILES): CC[C@@]1(c2ccccc2)NC(=O)N(Cc2ccccc2)C1=O
InChIKey: ZMZDHUHMXXALFX-SFHVURJKSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 294.35, ALogP 3.04, HBA 2, HBD 1, PSA 49.41, QED 0.88
Compound (SMILES): Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccnc4)c3F)c2c1
InChIKey: UPHZYLHTKYNCFG-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 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 428.42, ALogP 3.58, HBA 5, HBD 2, PSA 104.81, QED 0.47
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CCC4)cc12
InChIKey: AQTBQCHUFYSOQT-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase C316Y mutant in HCV genotype 1A infected in HuH7 cells after 40 hrs by Taqman probe based RT-PCR analysis
Measurement: EC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 626.69, ALogP 6.76, HBA 6, HBD 1, PSA 97.44, QED 0.23
Compound (SMILES): Cc1ccc2c(Nc3cccc(Cl)c3F)nccc2c1NC(=O)c1csc2c(N)ncnc12
InChIKey: KVCQTKNUUQOELD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-RAF V600E mutant (unknown origin)
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 478.94, ALogP 5.92, HBA 7, HBD 3, PSA 105.82, QED 0.3
Compound (SMILES): C[C@H](NS(=O)(=O)C1CC1)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccc(S(C)(=O)=O)cc1
InChIKey: YZCRFFWBUPSXGV-QLXKLKPCSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to ERbeta (unknown origin) by FP assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 543.64, ALogP 4.16, HBA 7, HBD 1, PSA 107.36, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2nccs2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LIJNMTKCVRVOGY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.607 nM (pChEMBL 8.180000305175781)
Descriptors: MW 482.57, ALogP 4.69, HBA 9, HBD 0, PSA 78.19, QED 0.32
Compound (SMILES): CCCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: OGLYLZSRSCUDKX-YMBRHYMPSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Displacement of [3H]PGE2 from from human EP4 receptor expressed in HEK293 cells membranes incubated for 60 mins
Measurement: Ki >= 3288 nM (pChEMBL 5.482999801635742)
Descriptors: MW 445.58, ALogP 5.16, HBA 5, HBD 2, PSA 87.07, QED 0.44
Compound (SMILES): C=CC(=O)NCC1CCNc2c(C(N)=O)c(-c3ccc(Oc4ccccc4)cc3)nn21
InChIKey: JTLIXOUWXJJHBC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 0.72 nM (pChEMBL 9.140000343322754)
Descriptors: MW 417.47, ALogP 3.1, HBA 6, HBD 3, PSA 111.27, QED 0.51
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CN2CCC[C@@H]2CO1
InChIKey: FSJDACURTSWGHC-CVEARBPZSA-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 475.38, ALogP 4.93, HBA 7, HBD 1, PSA 68.74, QED 0.54
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1Br
InChIKey: MHDLISQTCKOIGO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 393.28, ALogP 3.58, HBA 4, HBD 1, PSA 54.56, QED 0.81
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(N)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VLBGQZMNQXPCIK-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 = 147.91 nM (pChEMBL 6.829999923706055)
Descriptors: MW 490.57, ALogP 4.82, HBA 8, HBD 1, PSA 91.32, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2nnc(NCCO)o2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DTNHNJVOHCLYPS-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 = 9.55 nM (pChEMBL 8.020000457763672)
Descriptors: MW 502.54, ALogP 3.17, HBA 12, HBD 2, PSA 136.48, QED 0.29
Compound (SMILES): O=C([C@H]1CC[C@H](c2nnn[nH]2)CC1)N1CC[C@](c2ccc(C(F)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: WBIWHHCDLUJJER-UAVUOLJFSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Transactivation of human GAL4-fused LXRbeta expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 651.58, ALogP 5.5, HBA 6, HBD 1, PSA 108.91, QED 0.28
Compound (SMILES): COC(=O)CCN1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: ZEIOSBCSTUSZSU-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 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 521.4, ALogP 4.33, HBA 9, HBD 1, PSA 95.04, QED 0.41
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc(C)c4nnn(Cc5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: WUWSRFYMNKHGQF-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase C316Y mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 29.4 nM (pChEMBL 7.53000020980835)
Descriptors: MW 643.67, ALogP 5.26, HBA 8, HBD 1, PSA 127.4, QED 0.25
Compound (SMILES): CNc1cccnc1C#CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: GBUHYEIUDCVWCP-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 = 12.88 nM (pChEMBL 7.889999866485596)
Descriptors: MW 505.58, ALogP 4.67, HBA 9, HBD 1, PSA 90.22, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4CCCO)nc3c2)c1
InChIKey: SQVQLWPBVNLBGK-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 = 5.495 nM (pChEMBL 8.260000228881836)
Descriptors: MW 463.54, ALogP 3.1, HBA 9, HBD 2, PSA 105.76, QED 0.37
Compound (SMILES): O=C(NCc1cccc(-c2ccc(CS(=O)(=O)Cc3n[nH]c(=O)[nH]3)cc2)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: GTZKIGXVCZWIAR-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of recombinant human AMPA-activated MMP1 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.57, ALogP 2.05, HBA 7, HBD 4, PSA 170.53, QED 0.24
Compound (SMILES): COc1cc(CC(=O)NCC(NC(=O)C(CCCNC(=O)c2cccc(I)c2)NC(=O)C(Cc2ccc(C(F)(F)P(=O)(O)O)cc2)NC(=O)c2ccc(C)c(Br)c2)C(N)=O)ccc1O
InChIKey: PXNYEUGGRMYQLD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein phosphatase C (SINGLE PROTEIN), Homo sapiens
UniProt: P08575
Assay: Enzyme Kinetic Assay: PTP activity was assayed using p-nitrophenyl phosphate (pNPP) as a substrate in 3,3-dimethylglutarate buffer (50 mM 3,3-dimethylglutarate, pH 7.0, 1 mM EDTA, 150 mM NaCl, 2 mM DTT, 0.1 mg/mL BSA) at 25° C. The assays were performed in 96-well plates. Normally, to determine the IC50 values, the reaction was initiated by the addition of enzyme (final concentration at 10 nM) to a reaction mixture (0.2 mL) containing 2 mM (Km for the substrate) pNPP with various concentrations of inhibitors. The reaction rate was measured using a SpectraMax Plus 384 Microplate Spectrophotometer (Molecular Devices). To determine the mode of inhibition, the reactions were initiated by the addition of PTP-MEG2 to the reaction mixtures (0.2 mL) containing various concentrations of pNPP with different concentrations of the inhibitor 7.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1085.63
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QECODAPTOHJSRN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 0.8913 nM (pChEMBL 9.050000190734863)
Descriptors: MW 476.58, ALogP 3.54, HBA 9, HBD 2, PSA 97.56, QED 0.36
Compound (SMILES): COc1ccc(/C=C/C(=O)Nc2ccc(CN(C)Cc3ccccc3)cc2)cc1
InChIKey: DBXKIEJEFALTHY-SFQUDFHCSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured up to 180 secs by spectrophotometric analysis
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 386.5, ALogP 4.98, HBA 3, HBD 1, PSA 41.57, QED 0.56
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2cccc(C(F)(F)F)c2)cc1
InChIKey: UZKOHPYLAOHDTN-FSKZSRKQSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding Assay: The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4° C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2a , (5 nM) were performed in a 100 μl volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell harvester. The filters were washed 3 times with ice-cold buffer and oven dried for one hour. [3H-] PGE2 (specific activity 180 Ci mmol) was used as the radioligand for EP receptors. [3H] 17-phenyl PGF2a, was employed for FP receptor binding studies. Binding studies employing EP1, EP2, EP4 and FP receptors were performed in duplicate in at least three separate experiments. A 200 μl assay volume was used. Incubations w
Measurement: Ki = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 446.47, ALogP 5.09, HBA 3, HBD 2, PSA 74.6, QED 0.55
Compound (SMILES): COc1cc(OC)c(Cl)c(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1Cl
InChIKey: LMNYJDMVSCGLHG-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 = 1.905 nM (pChEMBL 8.720000267028809)
Descriptors: MW 474.35, ALogP 4.48, HBA 8, HBD 1, PSA 85.53, QED 0.42
Compound (SMILES): Cl.O=C1c2ccccc2CC1CCN1CCc2ccccc2C1
InChIKey: CPHLFSOSYDLNIN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor by liquid scintillation counting method
Measurement: Ki = 391 nM (pChEMBL 6.409999847412109)
Descriptors: MW 291.39, ALogP 3.49, HBA 2, HBD 0, PSA 20.31, QED 0.86
Compound (SMILES): COc1ccnc(C#CCN(c2ccc3ncc(-c4cnn(C)c4)nc3c2)c2c(F)c(OC)cc(OC)c2F)n1
InChIKey: JYQPFNMDHXKRKL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.862 nM (pChEMBL 8.729999542236328)
Descriptors: MW 543.53, ALogP 4.31, HBA 10, HBD 0, PSA 100.31, QED 0.28
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4OC)ccc3o2)cc1
InChIKey: GQPVWDHUHXFDMI-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 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 565.63, ALogP 5.11, HBA 8, HBD 2, PSA 136.83, QED 0.25
Compound (SMILES): CC(C)[C@@H]1c2nn(-c3ccc(CO)c(S(C)(=O)=O)c3)cc2CN1c1ncc(CO)c(C(F)(F)F)n1
InChIKey: HFGCUOYYZKNQLX-LJQANCHMSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 493 nM (pChEMBL 6.309999942779541)
Descriptors: MW 511.53, ALogP 2.79, HBA 9, HBD 2, PSA 121.44, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CCCN)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: IUNZJOJKNTUAGY-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 = 0.6166 nM (pChEMBL 9.210000038146973)
Descriptors: MW 446.56, ALogP 4.58, HBA 8, HBD 1, PSA 91.32, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(Cc2ccncc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IRABEPFZBWUTFB-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 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 452.52, ALogP 4.78, HBA 8, HBD 0, PSA 78.19, QED 0.35
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(OC)nc4OC)cc23)c1F
InChIKey: LFENFBGBXDFEOL-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 516.53, ALogP 4.3, HBA 7, HBD 2, PSA 123.27, QED 0.32
Compound (SMILES): COc1cn(C(CC2CCOC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: UPJPTNTVAMVKSD-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition Assay: Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μl in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 521.96, ALogP 4.35, HBA 7, HBD 2, PSA 130.65, QED 0.45
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(Cl)c(F)cc12
InChIKey: UDSAMCMJMDTOJQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 336.79, ALogP 3.6, HBA 3, HBD 1, PSA 45.33, QED 0.87
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H]2CCCN2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SYQCXJZLWMRWKD-SFHVURJKSA-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 = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 444.54, ALogP 3.94, HBA 8, HBD 1, PSA 77.33, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC(C)N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AHWOGVXLWKIELS-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 = 3.388 nM (pChEMBL 8.470000267028809)
Descriptors: MW 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)CN)c1
InChIKey: SOYCCBHGJYSWNQ-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 = 10 nM (pChEMBL 8)
Descriptors: MW 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(-c2ccccn2)cs1
InChIKey: JFLJVHMCZLMBSN-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 510.41, ALogP 6.79, HBA 8, HBD 1, PSA 82.05, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C5CCN(C(=O)OC(C)(C)C)CC5)c4)nc3c2)c1
InChIKey: SRQIALHPCHADMP-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 = 7.586 nM (pChEMBL 8.119999885559082)
Descriptors: MW 574.68, ALogP 5.21, HBA 10, HBD 1, PSA 115.07, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCCCN2)n1
InChIKey: FZGGLLMOLZVRHY-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 516.45, ALogP 6.54, HBA 8, HBD 2, PSA 81.19, QED 0.29
Compound (SMILES): COc1ncc(-c2ccc3ncnc(-c4cccc(C(=O)N5CCN(C(C)=O)CC5)c4)c3c2)cc1C#N
InChIKey: QYTXJLQBSYAMGR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K-delta (unknown origin) by KinaseGlo assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 492.54, ALogP 3.54, HBA 7, HBD 0, PSA 112.31, QED 0.43
Compound (SMILES): CCN1CCN(c2noc(COc3cc4ncnc(Nc5ccc(Cl)c(Cl)c5)c4cc3OC)n2)CC1
InChIKey: FGHXOSBHGQKMBX-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 530.42, ALogP 4.79, HBA 10, HBD 1, PSA 101.67, QED 0.34
Compound (SMILES): CC[C@@]1(c2ccccc2)NC(=O)N(Cc2ccccc2)C1=O
InChIKey: ZMZDHUHMXXALFX-SFHVURJKSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate incubated for 15 to 45 mins in presence of NADPH
Measurement: IC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 294.35, ALogP 3.04, HBA 2, HBD 1, PSA 49.41, QED 0.88
Compound (SMILES): Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccnc4)c3F)c2c1
InChIKey: UPHZYLHTKYNCFG-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 428.42, ALogP 3.58, HBA 5, HBD 2, PSA 104.81, QED 0.47
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CCC4)cc12
InChIKey: AQTBQCHUFYSOQT-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase S365A mutant in HCV genotype 1A infected in HuH7 cells after 40 hrs by Taqman probe based RT-PCR analysis
Measurement: EC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 626.69, ALogP 6.76, HBA 6, HBD 1, PSA 97.44, QED 0.23
Compound (SMILES): Cc1ccc2c(Nc3cccc(Cl)c3F)nccc2c1NC(=O)c1csc2c(N)ncnc12
InChIKey: KVCQTKNUUQOELD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase A-Raf (SINGLE PROTEIN), Homo sapiens
UniProt: P10398
Assay: Inhibition of ARAF (unknown origin)
Measurement: IC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 478.94, ALogP 5.92, HBA 7, HBD 3, PSA 105.82, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2nccs2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LIJNMTKCVRVOGY-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 = 10.23 nM (pChEMBL 7.989999771118164)
Descriptors: MW 482.57, ALogP 4.69, HBA 9, HBD 0, PSA 78.19, QED 0.32
Compound (SMILES): CCCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: OGLYLZSRSCUDKX-YMBRHYMPSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Displacement of [3H]PGE2 from from human EP2 receptor expressed in HEK293 cells at pH 7.3 membranes incubated for 60 mins
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 445.58, ALogP 5.16, HBA 5, HBD 2, PSA 87.07, QED 0.44
Compound (SMILES): C=CC(=O)NCC1CCNc2c(C(N)=O)c(-c3ccc(Oc4ccccc4)cc3)nn21
InChIKey: JTLIXOUWXJJHBC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 417.47, ALogP 3.1, HBA 6, HBD 3, PSA 111.27, QED 0.51
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CN2CCC[C@@H]2CO1
InChIKey: FSJDACURTSWGHC-CVEARBPZSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 475.38, ALogP 4.93, HBA 7, HBD 1, PSA 68.74, QED 0.54
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1Br
InChIKey: MHDLISQTCKOIGO-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
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 393.28, ALogP 3.58, HBA 4, HBD 1, PSA 54.56, QED 0.81
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(N)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VLBGQZMNQXPCIK-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 = 147.91 nM (pChEMBL 6.829999923706055)
Descriptors: MW 490.57, ALogP 4.82, HBA 8, HBD 1, PSA 91.32, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2nnc(NCCO)o2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DTNHNJVOHCLYPS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 502.54, ALogP 3.17, HBA 12, HBD 2, PSA 136.48, QED 0.29
Compound (SMILES): COC(=O)CCN1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: ZEIOSBCSTUSZSU-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 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 521.4, ALogP 4.33, HBA 9, HBD 1, PSA 95.04, QED 0.41
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc(C)c4nnn(Cc5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: WUWSRFYMNKHGQF-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase S365A mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 120.3 nM (pChEMBL 6.920000076293945)
Descriptors: MW 643.67, ALogP 5.26, HBA 8, HBD 1, PSA 127.4, QED 0.25
Compound (SMILES): CNc1cccnc1C#CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: GBUHYEIUDCVWCP-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 = 32.36 nM (pChEMBL 7.489999771118164)
Descriptors: MW 505.58, ALogP 4.67, HBA 9, HBD 1, PSA 90.22, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4CCCO)nc3c2)c1
InChIKey: SQVQLWPBVNLBGK-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 = 10.47 nM (pChEMBL 7.980000019073486)
Descriptors: MW 463.54, ALogP 3.1, HBA 9, HBD 2, PSA 105.76, QED 0.37
Compound (SMILES): O=C(NCc1cccc(-c2ccc(CS(=O)(=O)Cc3n[nH]c(=O)[nH]3)cc2)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: GTZKIGXVCZWIAR-UHFFFAOYSA-N
Target: Matrilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P09237
Assay: Inhibition of recombinant human AMPA-activated MMP7 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.57, ALogP 2.05, HBA 7, HBD 4, PSA 170.53, QED 0.24