lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ncc(-c2ccc3cnc(NC(=O)c4ccc(OC(C)C)cc4)cc3c2)n1C
InChIKey: JABLEWAOICNLML-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta kinase assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))].
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.48, ALogP 4.98, HBA 5, HBD 1, PSA 69.04, QED 0.51
Compound (SMILES): N#Cc1ccc(Nc2nccc(C(O)c3ccc(-c4ccc(C#N)cc4)cc3F)n2)cc1
InChIKey: RSDODWDGOTXMEA-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 28.5 nM (pChEMBL 7.539999961853027)
Descriptors: MW 421.44, ALogP 4.85, HBA 6, HBD 2, PSA 105.62, QED 0.48
Compound (SMILES): CC(=O)NC[C@@H]1OC(=O)N2c3cc(F)c(N4CCSCC4)cc3OC[C@@H]12
InChIKey: WZAVWVAEARSISR-HOCLYGCPSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes after 20 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 381.43, ALogP 1.6, HBA 6, HBD 1, PSA 71.11, QED 0.86
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2ncnc(Nc3ccc(C(=O)N4CCCCC4)cc3)n2)c1
InChIKey: PIDFACDPHSZEFT-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of SRC (unknown origin) by ADP-Glo assay
Measurement: IC50 = 524 nM (pChEMBL 6.28000020980835)
Descriptors: MW 443.51, ALogP 4.11, HBA 7, HBD 3, PSA 112.14, QED 0.47
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2cccc(-c3ccccc3)c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: AFDFLEMNTOCMSC-MREPYCEBSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 15.14 nM (pChEMBL 7.820000171661377)
Descriptors: MW 1100.3
Compound (SMILES): COc1cccc(F)c1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: CVDRGHAYCSOQSD-QHCPKHFHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 557.65, ALogP 5.91, HBA 6, HBD 3, PSA 109, QED 0.18
Compound (SMILES): COc1cc(-c2ccc(C#N)cc2)ccc1[C@H](O)c1ccnc(Nc2ccc(C#N)cc2)n1
InChIKey: UHMLHIRSNCDVOO-VWLOTQADSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 433.47, ALogP 4.72, HBA 7, HBD 2, PSA 114.85, QED 0.45
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(C5CCNCC5)c4)c3n2)cn1
InChIKey: YEFYCSKFDBXSSK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 324 nM (pChEMBL 6.489999771118164)
Descriptors: MW 358.45, ALogP 4.36, HBA 5, HBD 1, PSA 55.88, QED 0.59
Compound (SMILES): CN1CCC[C@H]1COc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(Br)cc2)cc1.Cl
InChIKey: VTAFHTQEZCYBMH-MCDYILNGSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG measured after 4 hrs by fluorescence polarization assay
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 506.48, ALogP 6.65, HBA 3, HBD 1, PSA 32.7, QED 0.33
Compound (SMILES): C/C(=N\NC(N)=S)c1nnn(-c2ccc(S(N)(=O)=O)cc2)c1C
InChIKey: ZSNUMVKUUMGBTC-VIZOYTHASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 7270 nM (pChEMBL 5.139999866485596)
Descriptors: MW 353.43, ALogP -0.22, HBA 7, HBD 3, PSA 141.28, QED 0.39
Compound (SMILES): O=C1NCCC12CCN(c1c(Cl)cncc1-c1cc3ccccc3s1)CC2
InChIKey: BVNDJEHETZIZCV-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide 4-hydroxylation as substrate by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 397.93, ALogP 4.72, HBA 4, HBD 1, PSA 45.23, QED 0.68
Compound (SMILES): CN(C)CCn1cc2cc(NC(=O)c3cccc(C(F)(F)F)n3)c(C(C)(C)O)cc2n1
InChIKey: QAOWCAZEVIIQTF-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 435.45, ALogP 3.49, HBA 6, HBD 2, PSA 83.28, QED 0.62
Compound (SMILES): Nc1n[nH]c(N2CCC(N3CCS(=O)(=O)C[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: CCZUIJXVLDHFRC-INIZCTEOSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Human AMCase Activity Assay: An enzymatic assay with recombinant human AMCase was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-Methylumbelliferyl B-D-N,N′-diacetylchitobioside hydrate was used as a substrate for the enzyme. Upon hydrolysis by AMCase, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of hAMCase recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Buffer (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 424.96, ALogP 1.35, HBA 7, HBD 2, PSA 108.21, QED 0.76
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4ccnc(N5CC6CC5CN6)c4)cc3c2)cn1
InChIKey: MEEQVGMKQTXGGV-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologies-a Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated ("0% Control") and phosphorylated ("100% control") forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 425.5, ALogP 2.83, HBA 7, HBD 2, PSA 87.97, QED 0.52
Compound (SMILES): O=C1c2ccc(F)cc2C(=O)C1(O)O
InChIKey: FGEXOKDSGCWVPT-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 38700 nM (pChEMBL 4.409999847412109)
Descriptors: MW 196.13, ALogP -0.11, HBA 4, HBD 2, PSA 74.6, QED 0.45
Compound (SMILES): CCCS(=O)(=O)Nc1cc(-c2cc(-c3ccc(N4CCNCC4)cc3)cnc2N)cc(F)c1OC
InChIKey: AMLGBGSXVKQKOZ-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of human recombinant RIPK2 (1 to 317 residues) expressed in Sf21 insect cells using MBP as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by ADP-Glo luminescence assay
Measurement: IC50 = 1.93 nM (pChEMBL 8.710000038146973)
Descriptors: MW 499.61, ALogP 3.71, HBA 7, HBD 3, PSA 109.58, QED 0.43
Compound (SMILES): CN1CCCN(c2cc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)ccn2)CC1
InChIKey: OPDWXCIBYSABOS-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 441.54, ALogP 3.42, HBA 7, HBD 1, PSA 79.18, QED 0.52
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(-c5cn[nH]c5)c4)c3n2)cn1
InChIKey: NVTNPVQFMSQPJQ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 1304 nM (pChEMBL 5.880000114440918)
Descriptors: MW 341.37, ALogP 4.29, HBA 5, HBD 1, PSA 72.53, QED 0.53
Compound (SMILES): CCN(CC)C(=O)/C=C/c1ccc(OC(=O)N(C)C)c(OC)c1
InChIKey: HSCGFHIZLBSWKK-PKNBQFBNSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 17800 nM (pChEMBL 4.75)
Descriptors: MW 320.39, ALogP 2.64, HBA 4, HBD 0, PSA 59.08, QED 0.76
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: HTTJWDFVHKLONF-LJDFNAPDSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 1055.21
Compound (SMILES): c1ccc(-c2coc3ccc(-c4cn[nH]c4)nc23)cc1
InChIKey: YJVHRHNVCYWWCM-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H422
Assay: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 261.28, ALogP 3.88, HBA 3, HBD 1, PSA 54.71, QED 0.6
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)(F)CO
InChIKey: MKAPFCBLWCECBI-GYCJOSAFSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis
Measurement: IC50 = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 488.56, ALogP 3.38, HBA 6, HBD 3, PSA 80.31, QED 0.43
Compound (SMILES): N#Cc1ccc(N2C3CCC2CN(C(=O)CCS(=O)(=O)c2cccc4ncsc24)C3)nc1
InChIKey: WKWYANDGYZVVAK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes assessed as inhibition constant incubated for 1 hr by Radioligand binding assay
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 467.58, ALogP 2.61, HBA 8, HBD 0, PSA 107.26, QED 0.57
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(OC)cc3)s2)cc1
InChIKey: NBWJYVUYQITPIR-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from rat adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 444.51, ALogP 5.31, HBA 6, HBD 1, PSA 77.52, QED 0.39
Compound (SMILES): COc1ccc(-c2cc(OC(C)=O)c3c(-c4cccs4)c(NC(=O)c4cccc(F)c4)oc3c2)cc1
InChIKey: FFSYPDOYYMJFKT-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of ABCB1 in FLp-In-293 cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 5 uM measured after 72 hrs by SRB assay (Rvb = 80 +/- 10 nM)
Measurement: IC50 = 81.8 nM (pChEMBL 7.090000152587891)
Descriptors: MW 501.54, ALogP 7.15, HBA 6, HBD 1, PSA 77.77, QED 0.2
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1cc(F)cc(F)c1
InChIKey: FXIHQUPVPUKVJH-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3kdelta in anti-IgD-induced human whole blood cells assessed as reduction in CD69 expression measured after 6 hrs by immunostaining based flow cytometric analysis
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 409.38, ALogP 3.86, HBA 7, HBD 2, PSA 105.44, QED 0.53
Compound (SMILES): CCNc1ncc2c(n1)N(C)CCN(c1ccc(COC(CCNC)c3ccccc3)cc1)C2=O
InChIKey: XAMXFOAGBMDRHS-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of human NET expressed in HEK293 cells assessed as reduction in ASP+ uptake incubated for 20 mins before ASP+ addition and measured after 90 mins by scintillation counting method
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 474.61, ALogP 3.87, HBA 7, HBD 2, PSA 82.62, QED 0.46
Compound (SMILES): O=C1/C(=N\Nc2nccs2)C(c2ccccc2)=NN1c1nc(-c2ccccc2)cs1
InChIKey: KYVZVVOQWWCVPP-MOHJPFBDSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate prewarmed for 10 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 19200 nM (pChEMBL 4.71999979019165)
Descriptors: MW 430.52, ALogP 4.49, HBA 8, HBD 1, PSA 82.84, QED 0.47
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4ccc(C(C)(C)C)cc4)c3n2)nn1
InChIKey: QCOJLKVLLTZZSA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 332.41, ALogP 4.59, HBA 5, HBD 0, PSA 56.74, QED 0.54
Compound (SMILES): C/C(=N\NC(N)=S)c1nnn(-c2ccc(F)cc2)c1C
InChIKey: BEPDFRPSNCPHCP-VIZOYTHASA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 292.34, ALogP 1.27, HBA 5, HBD 2, PSA 81.12, QED 0.51
Compound (SMILES): Nc1nn2c(-c3ccc([N+](=O)[O-])cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: XEDPDGPVDPXHDH-GHVJWSGMSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human full-length N-terminal GST/His6-tagged CDK9 (1 to 372 residues)/His6-tagged Cyclin-T1 (1 to 726 residues) expressed in sf9 cells using (YSPTSPS)2KK peptide as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 438.43, ALogP 2.95, HBA 10, HBD 2, PSA 184.23, QED 0.27
Compound (SMILES): Nc1nnc(-c2ccccc2O)cc1N1CCC[C@@H](O)C1
InChIKey: VUGYKDOKOLKKRA-SNVBAGLBSA-N
Target: Protein polybromo-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U86
Assay: Binding affinity to polybromo-1 (2) (unknown origin) by ITC analysis
Measurement: Kd = 252 nM (pChEMBL 6.599999904632568)
Descriptors: MW 286.33, ALogP 1.39, HBA 6, HBD 3, PSA 95.5, QED 0.77
Compound (SMILES): C#CCOc1ccc(-c2cc(-c3ccc(OCCN4CCOCC4)cc3)nc(N)n2)cc1
InChIKey: SZNDVDHYJXHIKM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE using acetylcholine as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by Amplex Red reagent based fluorescence assay
Measurement: IC50 = 30.46 nM (pChEMBL 7.519999980926514)
Descriptors: MW 430.51, ALogP 3.12, HBA 7, HBD 1, PSA 82.73, QED 0.55
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: JEWRIBSMLSEECE-HNNXBMFYSA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay
Measurement: Kd = 0.1 nM (pChEMBL 10)
Descriptors: MW 456.47, ALogP 5.08, HBA 6, HBD 3, PSA 91.66, QED 0.4
Compound (SMILES): COCCNc1cc(NC(=O)N(C)c2ccc(CN3CCN(C)CC3=O)c(C=O)n2)ncc1C#N
InChIKey: WMIQOTMTEKRJFD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition Assay: FGFR4:The in vitro activity of FGFR4 was determined by assaying the phosphorylation level of the substrate in the kinase reaction, by means of an HTRF kinase assay kit. The reaction buffer comprised the following components: 5-fold diluted Enzymatic buffer/kinase 5×(main ingredient: 50 mM HEPES, pH 7.0), 5 mM MgCl2, 1 mM DTT; the human recombinant FGFR4 catalytic structural domain protein (amino acids 460-802), diluted with the reaction buffer to a 0.5 ng/μL kinase solution; the substrate reaction solution comprised a biotin labeled tyrosine kinase substrate diluted with the reaction buffer to 500 nM , and 90 μM ATP, and the assay solution comprised an Eu3+ labeled cage-shaped antibody diluted with the assay buffer to 0.125 ng/μL, and 31.25 nM streptavidin labeled XL665).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 480.53, ALogP 1.16, HBA 9, HBD 2, PSA 143.79, QED 0.4
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(C#N)cc4n3)C2)cc1
InChIKey: ZRLQOLZZVDTUEA-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 412.45, ALogP 2.95, HBA 6, HBD 2, PSA 111.01, QED 0.62
Compound (SMILES): CC1(C)Cc2cccc(OCCNCC3(F)CCN(C(=O)c4ccc(F)c(Cl)c4)CC3)c2O1
InChIKey: BXPJDTCYZQOTIA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 6.607 nM (pChEMBL 8.180000305175781)
Descriptors: MW 478.97, ALogP 4.81, HBA 4, HBD 1, PSA 50.8, QED 0.58
Compound (SMILES): CNC(=O)c1ccc(C(=O)Nc2cc3cc(-c4cn(C)nn4)ccc3cn2)cn1
InChIKey: OSANCNYWHBAIGR-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The DYRK1A kinase assa: Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 387.4, ALogP 2.04, HBA 7, HBD 2, PSA 114.69, QED 0.55
Compound (SMILES): CCCCN(Cc1ccccc1)C(=O)c1ccc(S(=O)(=O)Nc2ccccc2)cc1
InChIKey: VNCIWNGCMAKKEO-UHFFFAOYSA-N
Target: LIM domain kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53667
Assay: Inhibition of LIMK1 in human HeLa cells lysate incubated for 45 mins by kinobead based pulldown assay
Measurement: IC50 = 824 nM (pChEMBL 6.079999923706055)
Descriptors: MW 422.55, ALogP 4.93, HBA 3, HBD 1, PSA 66.48, QED 0.53
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)c(C(F)(F)F)c2)cc1Oc1nc(-c2cccnc2)nc2[nH]ncc12
InChIKey: JCCUAVDBGXASEC-UHFFFAOYSA-N
Target: Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of KIF5B-RET fusion protein (unknown origin) by radiometric assay
Measurement: IC50 = 8.86 nM (pChEMBL 8.050000190734863)
Descriptors: MW 602.62, ALogP 5.53, HBA 8, HBD 2, PSA 112.16, QED 0.25
Compound (SMILES): CCOc1ccc2c(c1[C@H]1C[C@@H]1CN)CCO2.Cl
InChIKey: CZVVNGCGYYHXBE-XQKZEKTMSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 233.31, ALogP 2.08, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): COc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: NHWLXSUOSUTBMY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 455.36, ALogP 4.61, HBA 4, HBD 1, PSA 50.8, QED 0.59
Compound (SMILES): Nc1nc(Nc2ccc(F)c(Cl)c2)c2ncn(Cc3ccc(C(=O)Nc4ccccc4N)cc3)c2n1
InChIKey: BWFYYTOGYBJCQR-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human recombinant HDAC4 expressed in baculovirus using fluorogenic peptide p53 residues 379-382 (RHKK(Ac)AMC) as substrate by Fluorescence analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 502.94, ALogP 4.83, HBA 8, HBD 4, PSA 136.77, QED 0.24
Compound (SMILES): Cc1ccc(S(=O)(=O)n2cc(-c3ccc(C(F)(F)F)cc3)c3ccc(CO[C@H](C(=O)O)[C@H](N)C(=O)O)cc32)cc1.O=C(O)C(F)(F)F
InChIKey: ZWFTYWHNQILZJM-UKOKCHKQSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 transfected in HEK293 cells assessed as inhibition of [3H]-D-aspartate uptake incubated for 4 mins by TopCount scintillation counting analysis
Measurement: IC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 576.55, ALogP 4.25, HBA 7, HBD 3, PSA 148.92, QED 0.27
Compound (SMILES): CNC1CN(c2nc3ncc(Br)cc3n3nnnc23)C1
InChIKey: ICGICUHMULRYIQ-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q91ZY2
Assay: Antagonist activity at recombinant mouse histamine H4 receptor expressed in CHO-K1 cells assessed as inhibition of R-alpha-methylhistamine induced stimulation of [35S]-GTPgammaS binding by scintillation proximity assay
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 335.17, ALogP 0.24, HBA 8, HBD 1, PSA 84.13, QED 0.72
Compound (SMILES): Nc1nn2c(-c3ccc(F)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: PEGVFQMGKHGCER-WCWDXBQESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human full-length N-terminal GST/His6-tagged CDK9 (1 to 372 residues)/His6-tagged Cyclin-T1 (1 to 726 residues) expressed in sf9 cells using (YSPTSPS)2KK peptide as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 411.42, ALogP 3.18, HBA 8, HBD 2, PSA 141.09, QED 0.5
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2cnc(CN3CCC4(C=Cc5ccccc54)CC3)s2)cc1
InChIKey: LJLSDEMEFGKOKZ-DEOSSOPVSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full length GPR40 overexpressed in human HEK293 cells assessed as increase in inositol phosphate accumulation in presence of terbium cryptate-labeled anti IP1/d2-labelled IP1 measured after 120 mins by HTRF assay
Measurement: EC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 498.65, ALogP 5.86, HBA 5, HBD 1, PSA 62.66, QED 0.39
Compound (SMILES): C=CCOc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: CSTYJUKZFXDVEQ-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 243.31, ALogP 3.06, HBA 3, HBD 1, PSA 48.39, QED 0.82
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCN2CCC(Cc3ccccc3)CC2)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C1=O
InChIKey: FLFNAHDPAHKVGI-ZKUUFLNTSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Antagonist potency at human NPFFR2 expressed in CHO cell membrane assessed as inhibition of NPVF induced cAMP response incubated for 1 hr by Topcount counting method
Measurement: Kd = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 1014.29
Compound (SMILES): COc1cc(OC)c2c(N3CCS(=O)(=O)CC3)nc(-c3cc(C)c(OCCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: YRUAJZFECDBHMT-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC4 (627 to end residues) expressed in baculovirus infected Sf9 insect cells using AcLeu-Gly-Lys(Tfa)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 572.68, ALogP 3.61, HBA 10, HBD 2, PSA 140.18, QED 0.2
Compound (SMILES): COc1cc(OC)cc(-c2noc(N3CCN(C)C4(CCN(c5ccnc(C)c5)CC4)C3)n2)c1
InChIKey: NZYTZRHHBAJPKN-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase PRDM9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQV7
Assay: Affinity On-target Cellular interaction (Western Blot (inhibition of PRDM9-dependent trimethylation of ectopic H3K4 in HEK293T cells)) EUB0000234b PRDM9
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 464.57, ALogP 3.25, HBA 9, HBD 0, PSA 79.99, QED 0.57
Compound (SMILES): C[C@@H](c1ccc2ncccc2c1)c1nnc2sc(-c3cnn(C)c3)nn12
InChIKey: AMVSPCWTSDZDPI-NSHDSACASA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of SRC (unknown origin)
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 361.43, ALogP 3.29, HBA 8, HBD 0, PSA 73.79, QED 0.49
Compound (SMILES): CS(=O)(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: NUMHIIKAGFNIFT-NSHDSACASA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay
Measurement: Kd = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): COP(C)(=O)NCCCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1
InChIKey: PNWWIOCNZXFHEC-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells using L-tryptophan as substrate incubated for 48 hrs by absorbance based analysis
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 465.22, ALogP 3.08, HBA 8, HBD 4, PSA 133.9, QED 0.11
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CCCC(=O)Nc2ccc(C3CC3N)cc2)cc1
InChIKey: TYTLARZOLKJSJU-UHFFFAOYSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UKL0
Assay: Inhibition of LSD1/FLAG-tagged CoREST (unknown origin) expressed in HEK293F cells using diMeK4H3(1 to 21) as substrate preincubated for 5 mins followed by substrate addition measured for 5 mins by horseradish peroxidase-coupled assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 428.54, ALogP 4.3, HBA 4, HBD 4, PSA 110.24, QED 0.4
Compound (SMILES): Cc1ncc(-c2ccc3cnc(NC(=O)c4ccc(OC(C)C)cc4)cc3c2)n1C
InChIKey: JABLEWAOICNLML-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 684 nM (pChEMBL 6.170000076293945)
Descriptors: MW 400.48, ALogP 4.98, HBA 5, HBD 1, PSA 69.04, QED 0.51
Compound (SMILES): CC(=O)NC[C@@H]1OC(=O)N2c3cc(F)c(N4CCSCC4)cc3OC[C@@H]12
InChIKey: WZAVWVAEARSISR-HOCLYGCPSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells by whole cell manual patch clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 381.43, ALogP 1.6, HBA 6, HBD 1, PSA 71.11, QED 0.86
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2ncnc(Nc3ccc(C(=O)N4CCCCC4)cc3)n2)c1
InChIKey: PIDFACDPHSZEFT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human TMD8 cells assessed as reduction in cell proliferation incubated for 24 hrs by CCK-8 assay
Measurement: IC50 = 4360 nM (pChEMBL 5.360000133514404)
Descriptors: MW 443.51, ALogP 4.11, HBA 7, HBD 3, PSA 112.14, QED 0.47
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2cccc(-c3ccccc3)c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: AFDFLEMNTOCMSC-MREPYCEBSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 15.08 nM (pChEMBL 7.820000171661377)
Descriptors: MW 1100.3
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(C5CCNCC5)c4)c3n2)cn1
InChIKey: YEFYCSKFDBXSSK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 358.45, ALogP 4.36, HBA 5, HBD 1, PSA 55.88, QED 0.59
Compound (SMILES): C/C(=N\NC(N)=S)c1nnn(-c2ccc(S(N)(=O)=O)cc2)c1C
InChIKey: ZSNUMVKUUMGBTC-VIZOYTHASA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 353.43, ALogP -0.22, HBA 7, HBD 3, PSA 141.28, QED 0.39
Compound (SMILES): O=C1NCCC12CCN(c1c(Cl)cncc1-c1cc3ccccc3s1)CC2
InChIKey: BVNDJEHETZIZCV-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan O-demethylation as substrate by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 397.93, ALogP 4.72, HBA 4, HBD 1, PSA 45.23, QED 0.68
Compound (SMILES): CN(C)CCn1cc2cc(NC(=O)c3cccc(C(F)(F)F)n3)c(C(C)(C)O)cc2n1
InChIKey: QAOWCAZEVIIQTF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using midazolam as substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 435.45, ALogP 3.49, HBA 6, HBD 2, PSA 83.28, QED 0.62
Compound (SMILES): Nc1n[nH]c(N2CCC(N3CCS(=O)(=O)C[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: CCZUIJXVLDHFRC-INIZCTEOSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 424.96, ALogP 1.35, HBA 7, HBD 2, PSA 108.21, QED 0.76
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4ccnc(N5CC6CC5CN6)c4)cc3c2)cn1
InChIKey: MEEQVGMKQTXGGV-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 425.5, ALogP 2.83, HBA 7, HBD 2, PSA 87.97, QED 0.52
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(-c5cn[nH]c5)c4)c3n2)cn1
InChIKey: NVTNPVQFMSQPJQ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of human full length recombinant DYRK2 using casein substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 341.37, ALogP 4.29, HBA 5, HBD 1, PSA 72.53, QED 0.53
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)(F)CO
InChIKey: MKAPFCBLWCECBI-GYCJOSAFSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluormone ES2 green reagent from human GST-tagged ERalpha LBD (282 to 595 residues) expressed in baculovirus infected insect cells incubated for 1 hrs by TR-FRET Lanthascreen assay
Measurement: IC50 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 488.56, ALogP 3.38, HBA 6, HBD 3, PSA 80.31, QED 0.43
Compound (SMILES): N#Cc1ccc(N2C3CCC2CN(C(=O)CCS(=O)(=O)c2cccc4ncsc24)C3)nc1
InChIKey: WKWYANDGYZVVAK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M1 expressed in CHO-K1 cell membranes assessed as inhibition constant incubated for 1 hr by Radioligand binding assay
Measurement: Ki = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 467.58, ALogP 2.61, HBA 8, HBD 0, PSA 107.26, QED 0.57
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(OC)cc3)s2)cc1
InChIKey: NBWJYVUYQITPIR-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 444.51, ALogP 5.31, HBA 6, HBD 1, PSA 77.52, QED 0.39
Compound (SMILES): COc1ccc(-c2cc(OC(C)=O)c3c(-c4cccs4)c(NC(=O)c4cccc(F)c4)oc3c2)cc1
InChIKey: FFSYPDOYYMJFKT-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of human full-length ABCB1 expressed in FLp-In-293 cells assessed as potentiation of vincristine-induced cytotoxicity by measuring vincristine IC50 at 2.5 uM measured after 72 hrs by SRB assay (Rvb = 823 +/- 16 nM)
Measurement: IC50 = 96.2 nM (pChEMBL 7.019999980926514)
Descriptors: MW 501.54, ALogP 7.15, HBA 6, HBD 1, PSA 77.77, QED 0.2
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1cc(F)cc(F)c1
InChIKey: FXIHQUPVPUKVJH-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3kdelta in anti-IgD-induced human whole blood cells assessed as reduction in Akt phosphorylation at ser 473 residue pretreated with compound for 60 mins followed by anti-IgD stimulation measured after 7 mins by Alexa fluor 488 staining based flow cytometry analysis
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 409.38, ALogP 3.86, HBA 7, HBD 2, PSA 105.44, QED 0.53
Compound (SMILES): O=C1/C(=N\Nc2nccs2)C(c2ccccc2)=NN1c1nc(-c2ccccc2)cs1
InChIKey: KYVZVVOQWWCVPP-MOHJPFBDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate prewarmed for 10 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 2690 nM (pChEMBL 5.570000171661377)
Descriptors: MW 430.52, ALogP 4.49, HBA 8, HBD 1, PSA 82.84, QED 0.47
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4ccc(C(C)(C)C)cc4)c3n2)nn1
InChIKey: QCOJLKVLLTZZSA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of human full length recombinant DYRK2 using casein substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 332.41, ALogP 4.59, HBA 5, HBD 0, PSA 56.74, QED 0.54
Compound (SMILES): C#CCOc1ccc(-c2cc(-c3ccc(OCCN4CCOCC4)cc3)nc(N)n2)cc1
InChIKey: SZNDVDHYJXHIKM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition and measured after 15 mins by Ellman's method
Measurement: IC50 = 666 nM (pChEMBL 6.179999828338623)
Descriptors: MW 430.51, ALogP 3.12, HBA 7, HBD 1, PSA 82.73, QED 0.55
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: JEWRIBSMLSEECE-HNNXBMFYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 456.47, ALogP 5.08, HBA 6, HBD 3, PSA 91.66, QED 0.4
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(C#N)cc4n3)C2)cc1
InChIKey: ZRLQOLZZVDTUEA-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 412.45, ALogP 2.95, HBA 6, HBD 2, PSA 111.01, QED 0.62
Compound (SMILES): CC1(C)Cc2cccc(OCCNCC3(F)CCN(C(=O)c4ccc(F)c(Cl)c4)CC3)c2O1
InChIKey: BXPJDTCYZQOTIA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 0.3236 nM (pChEMBL 9.489999771118164)
Descriptors: MW 478.97, ALogP 4.81, HBA 4, HBD 1, PSA 50.8, QED 0.58