lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCN1CCCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: TUJUURQEVYFCIN-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 491.42, ALogP 5.57, HBA 7, HBD 1, PSA 68.74, QED 0.44
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccn(C)n3)c2c(=O)n1-c1ccccc1
InChIKey: VQWJJVZHAWENFG-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: PI3-Kinase HTRF Assay: A PI3-Kinase HTRF® assay kit (cat No. 33-016) purchased from Millipore Corporation was used to screen compounds provided herein. This assay used specific, high affinity binding of the GRP1 pleckstrin homology (PH) domain to PIP3, the product of a Class 1A or 1B PI3 Kinase acting on its physiological substrate PIP2. During the detection phase of the assay, a complex was generated between the GST-tagged PH domain and biotinylated short chain PIP3. The biotinylated PIP3 and the GST-tagged PH domain recruited fluorophores (Streptavidin-Allophycocyanin and Europium-labeled anti-GST respectively) to form the fluorescence resonance energy transfer (FRET) architecture, generating a stable time-resolved FRET signal. The FRET complex was disrupted in a competitive manner by non-biotinylated PIP3, a product formed in the PI3 Kinase assay.PI3 Kinase α, β, γ or δ activity was assayed using the PI3 Kinase HTRF® assay kit (catalogue No. 33-016) purchased from Millipore Corporation. Purified recombinant PI3Kα (catalogue No. 14-602-K), PI3Kβ (catalogue No. 14-603-K), PI3Kγ (catalogue No. 14-558-K), and PI3Kδ (catalogue No. 14-604-K) were obtained from Millipore Corporation. Purified recombinant PI3K enzyme was used to catalyze the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2 at 10 μM) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the presence of 10 μM ATP. The assay was carried out in 384-well format and detected using a Perkin Elmer EnVision Xcite Multilabel Reader. Emission ratios were converted into percent inhibitions and imported into GraphPad Prism software. The concentration necessary to achieve inhibition of enzyme activity by 50% (IC50) was calculated using concentrations ranging from 20 μM to 0.1 nM (12-point curve). IC50 values were determined using a nonlinear regression model available in GraphPad Prism 5.
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 528.58, ALogP 3.24, HBA 9, HBD 2, PSA 125.13, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(F)(F)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: XYDJGMNTBSEQFA-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 494.55, ALogP 4.91, HBA 7, HBD 1, PSA 79.4, QED 0.35
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCCC1CCCN1C
InChIKey: YAEMBTULTQVMDI-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 447.37, ALogP 5.55, HBA 6, HBD 1, PSA 59.51, QED 0.51
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1C(=O)c1ccnc(C(F)(F)F)c1F
InChIKey: LMDWZBQISRTEBH-QMMMGPOBSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.32, ALogP 2.34, HBA 7, HBD 0, PSA 89.69, QED 0.59
Compound (SMILES): COc1cc(OC)cc(N(CCCN2C[C@@H](C)O[C@@H](C)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WSEXAZBKZQGSDN-OYRHEFFESA-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 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 516.65, ALogP 4.68, HBA 9, HBD 0, PSA 77.77, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC(C)(C)O)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: VIMGDHNUHDOJNR-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 = 14.79 nM (pChEMBL 7.829999923706055)
Descriptors: MW 419.49, ALogP 3.95, HBA 7, HBD 2, PSA 96.39, QED 0.47
Compound (SMILES): COc1cc(OCC2CC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: AQKXHUNLOGKFNZ-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 = 537.03 nM (pChEMBL 6.269999980926514)
Descriptors: MW 455.56, ALogP 5.38, HBA 7, HBD 0, PSA 65.3, QED 0.34
Compound (SMILES): CN(C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1)c1ccc(F)cc1
InChIKey: XBVGWGDWJNHOQD-SHTZXODSSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 378.46, ALogP 4.15, HBA 5, HBD 1, PSA 62.11, QED 0.58
Compound (SMILES): COc1ccc(Cl)c(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: BBUCWORXTQFNRD-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 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 477.01, ALogP 5.32, HBA 7, HBD 0, PSA 59.31, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(C)(C)O)c4)nc3c2)c1
InChIKey: MTSOIUXASMCNHX-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 = 15.14 nM (pChEMBL 7.820000171661377)
Descriptors: MW 473.58, ALogP 4.83, HBA 8, HBD 1, PSA 85.53, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CCC2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AYJLMQKFNIMDMS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.57 nM (pChEMBL 8.59000015258789)
Descriptors: MW 472.59, ALogP 4.58, HBA 8, HBD 1, PSA 77.33, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(C/C=C/c2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SCXUCUKEHHIEDN-AATRIKPKSA-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 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 509.57, ALogP 4.7, HBA 10, HBD 0, PSA 100.31, QED 0.28
Compound (SMILES): Nc1ncc(-c2ncccc2OC(F)(F)F)nc1C(=O)Nc1ncccc1N1CCC(N)CC1
InChIKey: ISHUULBGXOVLLF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSKbeta Assay: Types of GSK-3 assay used to test the selectivity/off target potential compounds of the invention with respect to PKC Î±/Î¸ inhibition activity includes the following: Type 1: The GSK-3 specific peptide used in this assay was derived from the phosphorylation site of glycogen synthase and its sequence is: YRRAAVPPSPSLSRHSSPHQ(S)EDEEE (SEQ ID NO: 1). (S) is pre-phosphorylated as is glycogen synthase in vivo and the three consensus sites for GSK-3 specific phosphorylation are underlined. The buffer used to make up the glycogen synthase peptide and [γ-33P] ATP consisted of MOPS 25 mM, EDTA 0.2 mM, magnesium acetate 10 mM, Tween-20 0.01% and mercaptoethanol 7.5 mM at pH 7.00. The compounds were dissolved in dimethyl sulphoxide (DMSO) to a final concentration of 100 mM. Various concentrations were made up in DMSO and mixed with the substrate (GSK-3 peptide) solution (to a final concentration 20 uM) described in the above section along with rabbit or human GSK-3α and GSK-3β (final concentration 0.5 uM/mL enzyme). The reactions were initiated with the addition of [γ-33P] ATP (500 cpm/pmole) spiked into a mixture of ATP (final concentration of 10 uM). After 30 minutes at room temperature the reaction was terminated by the addition of 10 uL of H3PO4/O.OP/0 Tween-20 (2.5%). A volume (10 uL) of the mixture was spotted onto P-30 phosphocellulose paper (Wallac & Berthold, EG&G Instruments Ltd, Milton Keynes). The paper was washed four times in H3PO4 (0.5%), 2 minutes for each wash, air dried and the radioactive phosphate incorporated into the synthetic glycogen synthase peptide, which binds to the P-30 phosphocellulose paper, was counted in a Wallac microbeta scintillation counter Analysis of Data: Values for IC50 for each inhibitor were calculated by fitting a four-parameter logistic curve to the model: cpm=lower+(upper-lower)/(I+(concentration IC50)).
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 474.45, ALogP 2.59, HBA 9, HBD 3, PSA 145.17, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CN2CCC(F)(F)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JWLSSKVRBZFBNN-UHFFFAOYSA-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 = 208.93 nM (pChEMBL 6.679999828338623)
Descriptors: MW 524.57, ALogP 3.89, HBA 9, HBD 1, PSA 88.77, QED 0.35
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1
InChIKey: FHRWHNJJQGSCQC-LJAQVGFWSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Displacement of [3H]-(S)-2-(6-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid from human recombinant full-length GPR40 expressed in human HEK293 cell membrane assessed as dissociation constant measured after 2 hrs by radioligand competitive assay
Measurement: Kd = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 491.63, ALogP 6.41, HBA 3, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)n3)CC2)C1
InChIKey: QFPGZAJRDFHPCE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 536.52, ALogP 2.86, HBA 9, HBD 1, PSA 132.51, QED 0.41
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)(F)F)cc3)c(N)c2c1C
InChIKey: UDSFKIFLJPECRN-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 444.46, ALogP 3.11, HBA 7, HBD 2, PSA 115.04, QED 0.64
Compound (SMILES): C[C@H](NC(=O)C(F)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccccc1
InChIKey: UITKQZZSZUEHEA-NYHFZMIOSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transrepression of glucocorticoid receptor in human PBMC assessed as inhibition of LPS induced TNF alpha release preincubated for 45 mins followed by LPS addition measured after 18 hrs by ELISA
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 457.43, ALogP 5.35, HBA 4, HBD 1, PSA 56.15, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(C[C@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: INWHLZUNIJSPHA-QFIPXVFZSA-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 = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 473.46, ALogP 4.11, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4ccccc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: JHEVLALGAHRXET-BUVWRSTLSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for t-opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hr at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Count.
Measurement: Ki = 1.52 nM (pChEMBL 8.819999694824219)
Descriptors: MW 501.67, ALogP 5.14, HBA 5, HBD 0, PSA 40.16, QED 0.5
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(Cl)cc(Br)c12
InChIKey: JJRIZGWGCHCNHJ-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 397.7, ALogP 4.23, HBA 3, HBD 1, PSA 45.33, QED 0.79
Compound (SMILES): COC[C@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-ZMBIFBSDSA-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 = 3.631 nM (pChEMBL 8.4399995803833)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31
Compound (SMILES): CC(O)CN1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: MQDDJWTVOBHYHX-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of DAT (unknown origin) expressed in COS7 cells assessed as reduction in [3H]DA uptake incubated for 5 mins by beta-scintillation counting method
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 406.54, ALogP 3.79, HBA 4, HBD 1, PSA 26.71, QED 0.72
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)C=CSC(N)=N1
InChIKey: VLLFGVHGKLDDLW-SFHVURJKSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of CatD (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 367.41, ALogP 3.14, HBA 6, HBD 2, PSA 104.16, QED 0.87
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H]2C[C@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MPXSKHFKEUVGAU-IRXDYDNUSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.02 nM (pChEMBL 8.520000457763672)
Descriptors: MW 445.52, ALogP 3.81, HBA 8, HBD 1, PSA 85.53, QED 0.44
Compound (SMILES): COc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccnc4)c3F)c12
InChIKey: PFGJPPQAAOSHGL-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 444.42, ALogP 3.28, HBA 6, HBD 2, PSA 114.04, QED 0.44
Compound (SMILES): C=CC(=O)N1CC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2OC)C1
InChIKey: QIMXUZNKIMFXLS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Cell Viability Assay and IC50 Estimation: Cell viability was determined using the Cell Titer Glo assay (Promega) as previously described. Briefly, 2000-3000 cells per well were plated in 384-well plates (Greiner Bio-One) in technical triplicate. Cells were treated with seven different concentrations of tyrosine kinase inhibitors or vehicle alone at a final volume of 40 μL per well. After 3 days hours, 11 μL of Cell Titer Glo was added to each well. Plates were shaken for 15 minutes, and bioluminescence was determined using a FLUOstar OPTIMA multi-mode micro-plate reader (BMG LABTECH). Bioluminescence values were normalized to DMSO treated cells, and normalized values were plotted in GraphPad Prism using non-linear regression fit to normalized data with a variable slope. IC50 values were calculated by GraphPad Prism at 50% inhibition.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 463.3, ALogP 4.6, HBA 6, HBD 1, PSA 76.58, QED 0.43
Compound (SMILES): CCN(CC)Cc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LTGQGTOGUOJONG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 527.72, ALogP 5.5, HBA 8, HBD 0, PSA 62.55, QED 0.24
Compound (SMILES): COc1cc(O)ccc1-c1ccc2c(-c3nc4ccccc4[nH]3)n[nH]c2c1
InChIKey: GYKZZSDJTVJBHL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human GST-tagged CDK4/cyclin D1 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by gamma32P-ATP based scintillation counting analysis
Measurement: Ki = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 356.38, ALogP 4.49, HBA 4, HBD 3, PSA 86.82, QED 0.44
Compound (SMILES): CCCN1CCCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: TUJUURQEVYFCIN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
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 491.42, ALogP 5.57, HBA 7, HBD 1, PSA 68.74, QED 0.44
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccn(C)n3)c2c(=O)n1-c1ccccc1
InChIKey: VQWJJVZHAWENFG-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: PI3K-delta Selective Assay: A compound's ability in selectively inhibiting PI3K-δ can be assessed using RAJI cells, i.e., B lymphocyte cells derived from lymphoma patients. Briefly, serum-starved RAJI cells are stimulated with anti-human IgM, thereby causing signaling through the B-cell receptors, as described in, for example, He et al., Leukemia Research (2009) 33: 798-802. B-cell receptor signaling is important for the activation, differentiation, and survival of B cells and certain B-cell derived cancers. Reduction of phospho-AKT is indicative of compounds that may inhibit B-cell proliferation and function in certain diseases. By monitoring the reduction of phospho-AKT in stimulated RAJI cells (using for example, phospho-AKT antibodies), a compound's potential efficacy in selectively inhibiting PI3Kδ can be assessed.
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 528.58, ALogP 3.24, HBA 9, HBD 2, PSA 125.13, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(F)(F)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: XYDJGMNTBSEQFA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 14.45 nM (pChEMBL 7.840000152587891)
Descriptors: MW 494.55, ALogP 4.91, HBA 7, HBD 1, PSA 79.4, QED 0.35
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1C(=O)c1ccnc(C(F)(F)F)c1F
InChIKey: LMDWZBQISRTEBH-QMMMGPOBSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.32, ALogP 2.34, HBA 7, HBD 0, PSA 89.69, QED 0.59
Compound (SMILES): COc1cc(OC)cc(N(CCCN2C[C@@H](C)O[C@@H](C)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WSEXAZBKZQGSDN-OYRHEFFESA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.169 nM (pChEMBL 8.380000114440918)
Descriptors: MW 516.65, ALogP 4.68, HBA 9, HBD 0, PSA 77.77, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC(C)(C)O)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: VIMGDHNUHDOJNR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.467 nM (pChEMBL 8.350000381469727)
Descriptors: MW 419.49, ALogP 3.95, HBA 7, HBD 2, PSA 96.39, QED 0.47
Compound (SMILES): COc1cc(OCC2CC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: AQKXHUNLOGKFNZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 455.56, ALogP 5.38, HBA 7, HBD 0, PSA 65.3, QED 0.34
Compound (SMILES): COc1ccc(Cl)c(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: BBUCWORXTQFNRD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 51.29 nM (pChEMBL 7.289999961853027)
Descriptors: MW 477.01, ALogP 5.32, HBA 7, HBD 0, PSA 59.31, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(C)(C)O)c4)nc3c2)c1
InChIKey: MTSOIUXASMCNHX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.166 nM (pChEMBL 8.210000038146973)
Descriptors: MW 473.58, ALogP 4.83, HBA 8, HBD 1, PSA 85.53, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CCC2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AYJLMQKFNIMDMS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.138 nM (pChEMBL 8.670000076293945)
Descriptors: MW 472.59, ALogP 4.58, HBA 8, HBD 1, PSA 77.33, QED 0.4
Compound (SMILES): COc1cc(Nc2cc(Oc3ccc(NC(=O)Nc4cc(C(C)(C)C)cc(NS(C)(=O)=O)c4OC)c4ccccc34)ccn2)ccc1C(=O)O
InChIKey: QFXFIEVXAUEHEV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Inhibition Studies: ompounds of the invention were tested for inhibition of the human ether a go-go (hERG) channel using IonWorks patch clamp electrophysiology at Essen Bioscience (Welwyn Garden City, England).
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 699.79, ALogP 7.8, HBA 9, HBD 5, PSA 177.21, QED 0.09
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2ccc(Cl)cc12
InChIKey: MDDRPRHJXXDKKV-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 318.8, ALogP 3.46, HBA 3, HBD 1, PSA 45.33, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(C/C=C/c2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SCXUCUKEHHIEDN-AATRIKPKSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 26.92 nM (pChEMBL 7.570000171661377)
Descriptors: MW 509.57, ALogP 4.7, HBA 10, HBD 0, PSA 100.31, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CN2CCC(F)(F)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JWLSSKVRBZFBNN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of TEL-fused FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 72 hrs by Alamar blue assay
Measurement: IC50 = 6.166 nM (pChEMBL 8.210000038146973)
Descriptors: MW 524.57, ALogP 3.89, HBA 9, HBD 1, PSA 88.77, QED 0.35
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1
InChIKey: FHRWHNJJQGSCQC-LJAQVGFWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.63, ALogP 6.41, HBA 3, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)n3)CC2)C1
InChIKey: QFPGZAJRDFHPCE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 536.52, ALogP 2.86, HBA 9, HBD 1, PSA 132.51, QED 0.41
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)(F)F)cc3)c(N)c2c1C
InChIKey: UDSFKIFLJPECRN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-N-Methylscopolamine from human M1 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 444.46, ALogP 3.11, HBA 7, HBD 2, PSA 115.04, QED 0.64
Compound (SMILES): O=C1NC(=O)C2(CCC(C(=O)N3CC[C@](c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4)(S(=O)(=O)c4ccc(F)cc4)C3)CC2)N1
InChIKey: QJZRZLRWRGWGLC-ITNSIVGMSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human Gal4-fused RORbeta LBD (200 to 559 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 667.58, ALogP 4.79, HBA 5, HBD 2, PSA 112.65, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(C[C@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: INWHLZUNIJSPHA-QFIPXVFZSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.344 nM (pChEMBL 8.630000114440918)
Descriptors: MW 473.46, ALogP 4.11, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4ccccc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: JHEVLALGAHRXET-BUVWRSTLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 μg membrane protein (recombinant κ opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μl binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 hr at a temperature of about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by five filtration washes with 2001 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hours.
Measurement: Ki = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 501.67, ALogP 5.14, HBA 5, HBD 0, PSA 40.16, QED 0.5
Compound (SMILES): COC[C@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-ZMBIFBSDSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.413 nM (pChEMBL 8.850000381469727)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31
Compound (SMILES): CC(O)CN1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: MQDDJWTVOBHYHX-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Displacement of [3H]WIN35,428 from wild type human DAT expressed in COS7 cell membranes incubated for >90 mins by radioligand binding assay
Measurement: Ki = 101 nM (pChEMBL 7)
Descriptors: MW 406.54, ALogP 3.79, HBA 4, HBD 1, PSA 26.71, QED 0.72
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)C=CSC(N)=N1
InChIKey: VLLFGVHGKLDDLW-SFHVURJKSA-N
Target: Cathepsin E (SINGLE PROTEIN), Homo sapiens
UniProt: P14091
Assay: Inhibition of CatE (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 367.41, ALogP 3.14, HBA 6, HBD 2, PSA 104.16, QED 0.87
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H]2C[C@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MPXSKHFKEUVGAU-IRXDYDNUSA-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 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 445.52, ALogP 3.81, HBA 8, HBD 1, PSA 85.53, QED 0.44
Compound (SMILES): C=CC(=O)N1CC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2OC)C1
InChIKey: QIMXUZNKIMFXLS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Cell Viability Assay and IC50 Estimation: Cell viability was determined using the Cell Titer Glo assay (Promega) as previously described. Briefly, 2000-3000 cells per well were plated in 384-well plates (Greiner Bio-One) in technical triplicate. Cells were treated with seven different concentrations of tyrosine kinase inhibitors or vehicle alone at a final volume of 40 μL per well. After 3 days hours, 11 μL of Cell Titer Glo was added to each well. Plates were shaken for 15 minutes, and bioluminescence was determined using a FLUOstar OPTIMA multi-mode micro-plate reader (BMG LABTECH). Bioluminescence values were normalized to DMSO treated cells, and normalized values were plotted in GraphPad Prism using non-linear regression fit to normalized data with a variable slope. IC50 values were calculated by GraphPad Prism at 50% inhibition.
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 463.3, ALogP 4.6, HBA 6, HBD 1, PSA 76.58, QED 0.43
Compound (SMILES): CCN(CC)Cc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LTGQGTOGUOJONG-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 527.72, ALogP 5.5, HBA 8, HBD 0, PSA 62.55, QED 0.24
Compound (SMILES): CCCN1CCCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: TUJUURQEVYFCIN-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 491.42, ALogP 5.57, HBA 7, HBD 1, PSA 68.74, QED 0.44
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccn(C)n3)c2c(=O)n1-c1ccccc1
InChIKey: VQWJJVZHAWENFG-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: PI3K-gamma Selective Assay: A compound's ability in selectively inhibiting PI3K-γ can be assessed using RAW264.7 macrophages. Briefly, serum-starved RAW264.7 cells are stimulated with a known GPCR agonist C5a. See, e.g., Camps et al., Nature Medicine (2005) 11(9):936-943. Cells can be treated with test compounds prior to, simultaneously with, or subsequent to the stimulation by C5a. RAW 264.7 cells respond to the complement component fragment C5a through activation of the C5a receptor, and the C5a receptor activates macrophages and induces cell migration. Test compounds' ability to inhibit C5a-mediated AKT phosphorylation is indicative of selective inhibition of PI3K-γ. Thus, by monitoring the reduction of phospho-AKT in stimulated RAW 264.7 cells (using for example, phospho-AKT antibodies), a compound's potential efficacy in selectively inhibiting PI3Kγ can be assessed.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 528.58, ALogP 3.24, HBA 9, HBD 2, PSA 125.13, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(F)(F)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: XYDJGMNTBSEQFA-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 = 30.9 nM (pChEMBL 7.510000228881836)
Descriptors: MW 494.55, ALogP 4.91, HBA 7, HBD 1, PSA 79.4, QED 0.35
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1C(=O)c1ccnc(C(F)(F)F)c1F
InChIKey: LMDWZBQISRTEBH-QMMMGPOBSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.32, ALogP 2.34, HBA 7, HBD 0, PSA 89.69, QED 0.59
Compound (SMILES): COc1cc(OC)cc(N(CCCN2C[C@@H](C)O[C@@H](C)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WSEXAZBKZQGSDN-OYRHEFFESA-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 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 516.65, ALogP 4.68, HBA 9, HBD 0, PSA 77.77, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC(C)(C)O)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: VIMGDHNUHDOJNR-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 = 57.54 nM (pChEMBL 7.239999771118164)
Descriptors: MW 419.49, ALogP 3.95, HBA 7, HBD 2, PSA 96.39, QED 0.47
Compound (SMILES): COc1cc(OCC2CC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: AQKXHUNLOGKFNZ-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 455.56, ALogP 5.38, HBA 7, HBD 0, PSA 65.3, QED 0.34
Compound (SMILES): COc1ccc(Cl)c(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: BBUCWORXTQFNRD-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 = 245.47 nM (pChEMBL 6.610000133514404)
Descriptors: MW 477.01, ALogP 5.32, HBA 7, HBD 0, PSA 59.31, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(C)(C)O)c4)nc3c2)c1
InChIKey: MTSOIUXASMCNHX-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 = 52.48 nM (pChEMBL 7.28000020980835)
Descriptors: MW 473.58, ALogP 4.83, HBA 8, HBD 1, PSA 85.53, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CCC2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AYJLMQKFNIMDMS-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 = 10 nM (pChEMBL 8)
Descriptors: MW 472.59, ALogP 4.58, HBA 8, HBD 1, PSA 77.33, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(C/C=C/c2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SCXUCUKEHHIEDN-AATRIKPKSA-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 = 74.13 nM (pChEMBL 7.130000114440918)
Descriptors: MW 509.57, ALogP 4.7, HBA 10, HBD 0, PSA 100.31, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CC(O)CN2CCC(F)(F)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JWLSSKVRBZFBNN-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 = 281.84 nM (pChEMBL 6.550000190734863)
Descriptors: MW 524.57, ALogP 3.89, HBA 9, HBD 1, PSA 88.77, QED 0.35
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1
InChIKey: FHRWHNJJQGSCQC-LJAQVGFWSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human Gal4-fused PPARalpha LBD expressed in African green monkey CV1 cells cotransfected with pRL-SV40 plasmid measured after 24 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.63, ALogP 6.41, HBA 3, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)(F)F)cc3)c(N)c2c1C
InChIKey: UDSFKIFLJPECRN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-N-Methylscopolamine from human M2 receptor expressed in CHOK1 cells
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 444.46, ALogP 3.11, HBA 7, HBD 2, PSA 115.04, QED 0.64
Compound (SMILES): COc1cc(OC)cc(N(C[C@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: INWHLZUNIJSPHA-QFIPXVFZSA-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 = 11.75 nM (pChEMBL 7.929999828338623)
Descriptors: MW 473.46, ALogP 4.11, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4ccccc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: JHEVLALGAHRXET-BUVWRSTLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Dose-Displacement Binding Assay: Delta-opioid Receptor Binding Assay Procedures were conducted as follows. Radioligand dose-displacement assays used 0.3 nM [3H]-Naltrindole (Perkin Elmer, Shelton, Conn.; 33.0 Ci/mmole) with 5 ug membrane protein (Perkin Elmer, Shelton, Conn.) in a final volume of 500 ul binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 uM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 hr at a temperature of about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by five filtration washes with 500 ul ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hours.
Measurement: Ki = 15.01 nM (pChEMBL 7.820000171661377)
Descriptors: MW 501.67, ALogP 5.14, HBA 5, HBD 0, PSA 40.16, QED 0.5
Compound (SMILES): COC[C@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-ZMBIFBSDSA-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 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31
Compound (SMILES): CC(O)CN1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: MQDDJWTVOBHYHX-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN35428 from DAT in Sprague-Dawley rat striatal membranes incubated for 120 mins by microbeta scintillation counting method
Measurement: Ki = 37.8 nM (pChEMBL 7.420000076293945)
Descriptors: MW 406.54, ALogP 3.79, HBA 4, HBD 1, PSA 26.71, QED 0.72
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)C=CSC(N)=N1
InChIKey: VLLFGVHGKLDDLW-SFHVURJKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using ethoxyresorufin as substrate incubated for 15 mins in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 367.41, ALogP 3.14, HBA 6, HBD 2, PSA 104.16, QED 0.87