lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccc4F)CC3)cc2C1=O
InChIKey: JSYJUUGAOMCCSL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Receptor Binding Assay: 5-HT2A:(1) The prepared membrane was applied with buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use.(2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube.(3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of Methysergide (final concentration 10−5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10−5M) was added into the specific binding tube (SB) of each test compound.(4) 10 μL of radioactive ligand 3H-Ketanserin was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample).(5) Each of the reaction tubes was incubated at 37° C. for 15 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.(6) The scintillation vial were put into Liquid Scintillation Counter for counting.Inhibition rate(I%)=(Total binding tube cpm−compound cpm)/(Total binding tube cpm−nonspecific binding tube cpm)×100% .
Measurement: Ki = 32.1 nM (pChEMBL 7.489999771118164)
Descriptors: MW 397.49, ALogP 3.04, HBA 4, HBD 0, PSA 36.02, QED 0.7
Compound (SMILES): CO[C@@]12CC[C@H](N[C@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-VGDGPHSYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 254 nM (pChEMBL 6.590000152587891)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CC(F)(F)F)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: HJZVCQVBPMDUMS-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant CYP2D6 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 475.5, ALogP 4.7, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N2CCc3ccccc3C2)cc1
InChIKey: MWFZYRJWHFSLOE-JLHYYAGUSA-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 = 17700 nM (pChEMBL 4.75)
Descriptors: MW 364.45, ALogP 3.74, HBA 3, HBD 0, PSA 49.85, QED 0.78
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccccc2Cl)cc1
InChIKey: GJBRFDMGNAWWCF-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 39.3 nM (pChEMBL 7.409999847412109)
Descriptors: MW 432.91, ALogP 1.55, HBA 5, HBD 4, PSA 147.46, QED 0.52
Compound (SMILES): Cc1nc2cc(F)c(-c3cnc(C(C)(C)O)nc3)nc2c(N[C@H](C)c2cc(C#N)ccc2F)c1Cl
InChIKey: UDLNDXDUOBMZIQ-GFCCVEGCSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant CYP1A2 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 494.93, ALogP 5.6, HBA 7, HBD 2, PSA 107.61, QED 0.37
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-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 = 100 nM (pChEMBL 7)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4nn[nH]n4)nc23)cc1
InChIKey: ODCXYSYHXJMMPY-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 319.37, ALogP 3.97, HBA 5, HBD 1, PSA 80.49, QED 0.6
Compound (SMILES): Cc1cc(NC(=N)N)nc2ccccc12
InChIKey: PBIUQBDINOYEEJ-UHFFFAOYSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at human NPFFR2 by cell-based assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 200.25, ALogP 1.85, HBA 2, HBD 3, PSA 74.79, QED 0.49
Compound (SMILES): c1n[nH]cc1-c1ccc2occ(-c3ccc(C4CCCCC4)cc3)c2n1
InChIKey: PXEZKQRPUIYVRE-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 343.43, ALogP 5.93, HBA 3, HBD 1, PSA 54.71, QED 0.5
Compound (SMILES): O=S(=O)(c1cccc(Cl)c1)n1cnc2c(N3CCNCC3)nccc21
InChIKey: MMZBVOVVPMVDQY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L expressed in CHO-K1 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 377.86, ALogP 1.73, HBA 7, HBD 1, PSA 80.12, QED 0.75
Compound (SMILES): NC(=O)c1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: OODAUUFBIANTSD-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 = 38.02 nM (pChEMBL 7.420000076293945)
Descriptors: MW 451.9, ALogP 3.19, HBA 4, HBD 2, PSA 84.66, QED 0.6
Compound (SMILES): CN1CCc2cc(C(=O)Nc3cc4cc(-c5cn(C)nn5)ccc4cn3)ccc2C1
InChIKey: LZKASKVJGDNERL-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 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 398.47, ALogP 3.27, HBA 6, HBD 1, PSA 75.94, QED 0.57
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Antagonist activity at alphaVbeta5 in human MCF7 cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1nc(-c2ccc(NCC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: BTVYPZGQTDTPGE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 9450 nM (pChEMBL 5.03000020980835)
Descriptors: MW 515.56, ALogP 2.07, HBA 10, HBD 3, PSA 167.47, QED 0.28
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)Cc1ccc(O)cc1)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: JHLDGEVEPFCIIL-GSOVCQGVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (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 = 38.9 nM (pChEMBL 7.409999847412109)
Descriptors: MW 1115.33
Compound (SMILES): CC(C)Cc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: FFLMKLHRNAKIDD-CYBMUJFWSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Radioligand Binding Assay: Radioligand binding assays were performed using the commercially available 5-HT2 receptor agonist [125I]DOI as the radioligand and nonspecific binding was determined in the presence of unlabeled DOI at a saturating concentration of 10 μM. Competition experiments utilized 5-HT2 receptor expressing HEK293 cell membranes obtained as described in Example 3 (15-25 μg membrane protein/well) and radioligand at final assay concentrations of 0.4 to 0.6 nM. Experiments comprised addition of 95 μL of assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2), 50 μL of membranes, 50 μL of radioligand stock, and 5 μL of test compound diluted in assay buffer to 96-well microtiter plates, which were then incubated for 1 h at room temperature. Assay incubations were terminated by rapid filtration through PerkinElmer F/C filtration plates under reduced pressure using a 96-well Packard filtration apparatus, followed by washing three times with ice cold assay buffer. Plates were then dried at 45° C. for a minimum of 2 h. Finally, 25 μL of BetaScint scintillation cocktail was added to each well and the plates were counted in a Packard TopCount scintillation counter. In each competition study, test compounds were dosed at ten concentrations with triplicate determinations at each test concentration.
Measurement: Ki = 587 nM (pChEMBL 6.230000019073486)
Descriptors: MW 245.37, ALogP 2, HBA 3, HBD 1, PSA 28.16, QED 0.86
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of C-terminal 6xHis/FLAG-tagged full length human recombinant HDAC1 (1 to 482 end residues) expressed in Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 30 mins by fluorescence analysis
Measurement: IC50 = 92500 nM (pChEMBL 4.03000020980835)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using Ulight-labeled substrate by TR-FRET LANCE method
Measurement: IC50 > 320 nM (pChEMBL 6.494999885559082)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)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: LJFRRMYKCDZQBE-GSOVCQGVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (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 = 154.88 nM (pChEMBL 6.809999942779541)
Descriptors: MW 1126.29
Compound (SMILES): O=C1c2ccccc2/C=C\c2ccccc2N1CCCN1CCOCC1
InChIKey: FWCSMQRGFXNYQC-KHPPLWFESA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity to D2 receptor (unknown origin)
Measurement: Ki = 19100 nM (pChEMBL 4.71999979019165)
Descriptors: MW 348.45, ALogP 3.54, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-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 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CC(C)O)C(=O)NCc1ccc(F)cc1)c1sccc1C
InChIKey: LJMHAKIVRBTXAJ-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 85113.8 nM (pChEMBL 4.070000171661377)
Descriptors: MW 500.71, ALogP 5.78, HBA 5, HBD 2, PSA 52.57, QED 0.35
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccc(F)cc4)CC3)cc2C1=O
InChIKey: RMXGCHHYNPXIEU-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Receptor Binding Assay: 5-HT2A:(1) The prepared membrane was applied with buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use.(2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube.(3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of Methysergide (final concentration 10−5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10−5M) was added into the specific binding tube (SB) of each test compound.(4) 10 μL of radioactive ligand 3H-Ketanserin was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample).(5) Each of the reaction tubes was incubated at 37° C. for 15 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.(6) The scintillation vial were put into Liquid Scintillation Counter for counting.Inhibition rate(I%)=(Total binding tube cpm−compound cpm)/(Total binding tube cpm−nonspecific binding tube cpm)×100% .
Measurement: Ki = 688 nM (pChEMBL 6.159999847412109)
Descriptors: MW 397.49, ALogP 3.04, HBA 4, HBD 0, PSA 36.02, QED 0.7
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of alphavbeta3 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): O=C(O)C[C@@H](c1ccc(OCc2ccc3nc(-c4ccccc4)nn3c2)cc1)c1ccon1
InChIKey: KIZDOKWMTBVGAP-NRFANRHFSA-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 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 440.46, ALogP 4.57, HBA 7, HBD 1, PSA 102.75, QED 0.38
Compound (SMILES): Cc1cc(Cl)cc(-c2cnc3ncn(-c4cc(O)cc(F)c4)c(=O)c3c2CN(C)C[C@@H]2CCCN2)c1
InChIKey: YBLBKTUFAZAQNI-FQEVSTJZSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4
Measurement: EC50 = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 508, ALogP 4.44, HBA 7, HBD 2, PSA 83.28, QED 0.4
Compound (SMILES): C=CC(=O)N1CC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)CC1
InChIKey: AYGSWHUBBRQXAY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) using ULight - 4E - BP1( Thr37 / Thr46 ) as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 391.48, ALogP 3.23, HBA 4, HBD 2, PSA 90.98, QED 0.74
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cc3)nc2n2cc(C(C)C)nc12
InChIKey: DEVYXOKAXWLJRC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H (unknown origin)
Measurement: IC50 = 94.7 nM (pChEMBL 7.019999980926514)
Descriptors: MW 443.56, ALogP 4.07, HBA 8, HBD 2, PSA 87.45, QED 0.45
Compound (SMILES): c1ccc(-c2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: LDNVJIDFNXGSGT-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 337.38, ALogP 5.55, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): CN1CCN(c2cc(C(=O)Nc3cc4cc(-c5cnn(C)c5)c(F)cc4cn3)ccn2)CC1
InChIKey: XYOONDKQDDKZSA-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 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 445.5, ALogP 3.17, HBA 7, HBD 1, PSA 79.18, QED 0.52
Compound (SMILES): Cc1cc(CN)cc(C)c1-c1ncn(C)c1-c1ccnc2cc(F)ccc12
InChIKey: WOAOENGFAAUUGT-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZ95
Assay: Binding affinity to human NSD3 PWWP1 domain (247 to 398 residues) assessed as dissociation constant by SPR analysis
Measurement: Kd = 445 nM (pChEMBL 6.349999904632568)
Descriptors: MW 360.44, ALogP 4.52, HBA 4, HBD 1, PSA 56.73, QED 0.58
Compound (SMILES): CC(=O)N1CCc2nc(N3CCC(Oc4ccc(F)cc4F)CC3)c(N[C@@H]3CCOC3)nc2C1
InChIKey: HSWVJQBEXRKOBZ-QGZVFWFLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 473.52, ALogP 2.91, HBA 7, HBD 1, PSA 79.82, QED 0.72
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl GSK3B
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): c1ccc(Cc2cncc3c2CC[C@@H]2CNCCN32)cc1
InChIKey: YEAATRDZIJRTNR-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Radioligand Binding Assay: Radioligand binding assays were performed using the commercially available 5-HT2 receptor agonist [125I]DOI as the radioligand and nonspecific binding was determined in the presence of unlabeled DOI at a saturating concentration of 10 μM. Competition experiments utilized 5-HT2 receptor expressing HEK293 cell membranes obtained as described in Example 3 (15-25 μg membrane protein/well) and radioligand at final assay concentrations of 0.4 to 0.6 nM. Experiments comprised addition of 95 μL of assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2), 50 μL of membranes, 50 μL of radioligand stock, and 5 μL of test compound diluted in assay buffer to 96-well microtiter plates, which were then incubated for 1 h at room temperature. Assay incubations were terminated by rapid filtration through PerkinElmer F/C filtration plates under reduced pressure using a 96-well Packard filtration apparatus, followed by washing three times with ice cold assay buffer. Plates were then dried at 45° C. for a minimum of 2 h. Finally, 25 μL of BetaScint scintillation cocktail was added to each well and the plates were counted in a Packard TopCount scintillation counter. In each competition study, test compounds were dosed at ten concentrations with triplicate determinations at each test concentration.
Measurement: Ki = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 279.39, ALogP 2.4, HBA 3, HBD 1, PSA 28.16, QED 0.91
Compound (SMILES): O=C(Nc1cnn(-c2csc(C(=O)NC3COC3)c2)c1)Nc1c(F)cccc1Cl
InChIKey: ANCCTLHKRLRSAF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of JNK2 (unknown origin) by discoverX kinomescan assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 435.87, ALogP 3.5, HBA 6, HBD 3, PSA 97.28, QED 0.57
Compound (SMILES): C=CC(=O)N1CC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)C1
InChIKey: KPCQQZMELPQBCN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Binding affinity to CDK13 (unknown origin) by TR-FRET assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 377.45, ALogP 2.84, HBA 4, HBD 2, PSA 90.98, QED 0.76
Compound (SMILES): Cc1cccc(Cc2nc3cc(O[C@H]4CC[C@@H](C(=O)O)CC4)ccc3n2C)c1
InChIKey: OJYFETIOPQLONV-HDICACEKSA-N
Target: Long-chain-fatty-acid--CoA ligase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P41216
Assay: Inhibition of recombinant mouse ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 378.47, ALogP 4.49, HBA 4, HBD 1, PSA 64.35, QED 0.71
Compound (SMILES): COc1ccc(/C=C/C(=O)c2nnn(-c3ccc(Cl)cc3)c2C)cc1OC
InChIKey: YOJHPSLHBFFDDL-ONNFQVAWSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR in human RPMI-8226 cells incubated for 2 hrs by ELISA
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 383.83, ALogP 4.14, HBA 6, HBD 0, PSA 66.24, QED 0.47
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: Alpha-2B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18089
Assay: GPCRScan assay: inhibition of Alpha2B
Measurement: Ki = 2570.4 nM (pChEMBL 5.590000152587891)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of C-terminal 6His-tagged recombinant human STAT3 (127 to 711 residues) DNA-binding activity transfected in v-Src transformed mouse NIH3T3 cell nuclear extract preincubated for 10 mins followed by addition of radiolabeled hSIE and measured after 30 mins by EMSA analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(C5CNCCN5)cc4)ccn23)c2cc(F)cc(F)c2n1
InChIKey: UBTPOMHEYRBEHT-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: O00238
Assay: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 188 nM (pChEMBL 6.730000019073486)
Descriptors: MW 455.51, ALogP 5.04, HBA 5, HBD 2, PSA 54.25, QED 0.4
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)c(-c2ccccn2)s1)c1ccccc1
InChIKey: VMBMZXSGMDQSHW-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 357.44, ALogP 5.12, HBA 4, HBD 1, PSA 54.88, QED 0.55
Compound (SMILES): CNC(=O)c1ccc(N2CCN(c3cccc(C(=O)NC4C5CC6CC4CC(O)(C6)C5)n3)[C@H](C)C2)cn1
InChIKey: LJKNHXPUBONUPU-HRMXCHKUSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in pooled human liver microsomes using midazolam as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 504.64, ALogP 2.22, HBA 7, HBD 3, PSA 110.69, QED 0.57
Compound (SMILES): C=CC(=O)NC1CCC(c2ccc(C(C)C(=O)Nc3cc(C4CC4)n[nH]3)cc2)CC1
InChIKey: OUDPXOAJUACLFI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Binding affinity to CDK13 (unknown origin) by TR-FRET assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 406.53, ALogP 4.36, HBA 3, HBD 3, PSA 86.88, QED 0.6
Compound (SMILES): COc1ccc2cc(C(=O)OCCN3CCOCC3)oc2c1
InChIKey: OTWOITAHBIZVDR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using testosterone as substrate (Rvb = 0.0227 uM)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 305.33, ALogP 1.93, HBA 6, HBD 0, PSA 61.14, QED 0.79
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2occc12
InChIKey: JMBNFFBZCFTGQK-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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 249.28, ALogP 2.84, HBA 3, HBD 1, PSA 48.39, QED 0.89
Compound (SMILES): CC(C)S(=O)(=O)c1ccc2nccc(Nc3ccc4scnc4c3)c2c1
InChIKey: ZCDBTQNFAPKACC-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of N-terminal polyHis-tagged human RIPK2 (8 to 310 residues) expressed in Sf9 cells using MBP as substrate preincubated for 15 mins followed by ATP addition measured after 90 mins by ADP-Glo assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 383.5, ALogP 4.77, HBA 6, HBD 1, PSA 71.95, QED 0.55
Compound (SMILES): Cc1ccc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: CILYORNSOFTGAH-UHFFFAOYSA-N
Target: Lysophosphatidylserine lipase ABHD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N2K0
Assay: Inhibition of human ABHD12 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 356.44, ALogP 3.8, HBA 3, HBD 1, PSA 51.1, QED 0.85
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)C(OC(=O)c4ccc(F)cc4)C(C)(C)C)cc3F)c2cc1OC
InChIKey: FVPYEAORCOKOLV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Inhibition of Flt4 (unknown origin)
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 550.56, ALogP 6.53, HBA 7, HBD 1, PSA 95.98, QED 0.25
Compound (SMILES): O=C1NCCC12CCN(c1c(Cl)cncc1-c1cc3ccccc3o1)CC2
InChIKey: ILMHDRGZABQLEW-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 381.86, ALogP 4.25, HBA 4, HBD 1, PSA 58.37, QED 0.72
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccc4F)CC3)cc2C1=O
InChIKey: JSYJUUGAOMCCSL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Receptor Binding Assay: 5-HT7: (1) The prepared membrane was applied with buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of (��)-pindolol (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-5-CT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each of the reaction tubes was incubated at 25° C. for 120 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 29.9 nM (pChEMBL 7.519999980926514)
Descriptors: MW 397.49, ALogP 3.04, HBA 4, HBD 0, PSA 36.02, QED 0.7
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CC(F)(F)F)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: HJZVCQVBPMDUMS-UHFFFAOYSA-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 patch clamp assay
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 475.5, ALogP 4.7, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): Cc1nc2cc(F)c(-c3cnc(C(C)(C)O)nc3)nc2c(N[C@H](C)c2cc(C#N)ccc2F)c1Cl
InChIKey: UDLNDXDUOBMZIQ-GFCCVEGCSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of recombinant CYP2C8 (unknown origin)
Measurement: IC50 > 6700 nM (pChEMBL 5.173999786376953)
Descriptors: MW 494.93, ALogP 5.6, HBA 7, HBD 2, PSA 107.61, QED 0.37
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-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 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4nn[nH]n4)nc23)cc1
InChIKey: ODCXYSYHXJMMPY-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 319.37, ALogP 3.97, HBA 5, HBD 1, PSA 80.49, QED 0.6
Compound (SMILES): c1n[nH]cc1-c1ccc2occ(-c3ccc(C4CCCCC4)cc3)c2n1
InChIKey: PXEZKQRPUIYVRE-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 343.43, ALogP 5.93, HBA 3, HBD 1, PSA 54.71, QED 0.5
Compound (SMILES): NC(=O)c1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: OODAUUFBIANTSD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Receptor Binding Assay: 5-HT1A: Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human 5-HT1A receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-8-OH-DPAT (final concentration 1 nM, Kd 0.8 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 0.1 mM EDTA, 0.1% ascorbic acid) were transferred to polypropylene 96-well microplate using 96-wells pipetting station Rainin Liquidator (MettlerToledo). Serotonin (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 27° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 451.9, ALogP 3.19, HBA 4, HBD 2, PSA 84.66, QED 0.6
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Agonist activity at alphaVbeta6 in human HT-29 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1nc(-c2ccc(NCC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: BTVYPZGQTDTPGE-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 515.56, ALogP 2.07, HBA 10, HBD 3, PSA 167.47, QED 0.28
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)Cc1ccc(O)cc1)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: JHLDGEVEPFCIIL-GSOVCQGVSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (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 = 301.3 nM (pChEMBL 6.519999980926514)
Descriptors: MW 1115.33
Compound (SMILES): CC(C)Cc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: FFLMKLHRNAKIDD-CYBMUJFWSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Radioligand Binding Assay: Radioligand binding assays were performed using the commercially available 5-HT2 receptor agonist [125I]DOI as the radioligand and nonspecific binding was determined in the presence of unlabeled DOI at a saturating concentration of 10 μM. Competition experiments utilized 5-HT2 receptor expressing HEK293 cell membranes obtained as described in Example 3 (15-25 μg membrane protein/well) and radioligand at final assay concentrations of 0.4 to 0.6 nM. Experiments comprised addition of 95 μL of assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2), 50 μL of membranes, 50 μL of radioligand stock, and 5 μL of test compound diluted in assay buffer to 96-well microtiter plates, which were then incubated for 1 h at room temperature. Assay incubations were terminated by rapid filtration through PerkinElmer F/C filtration plates under reduced pressure using a 96-well Packard filtration apparatus, followed by washing three times with ice cold assay buffer. Plates were then dried at 45° C. for a minimum of 2 h. Finally, 25 μL of BetaScint scintillation cocktail was added to each well and the plates were counted in a Packard TopCount scintillation counter. In each competition study, test compounds were dosed at ten concentrations with triplicate determinations at each test concentration.
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 245.37, ALogP 2, HBA 3, HBD 1, PSA 28.16, QED 0.86
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of human full length C-terminal Flag tagged HDAC11 expressed in HEK293T cells assessed as reduction in demyristoylation activity using H3K9-myristoyl peptide as substrate by HPLC method
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin) by TR-FRET assay
Measurement: IC50 > 320 nM (pChEMBL 6.494999885559082)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)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: LJFRRMYKCDZQBE-GSOVCQGVSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (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 = 289.1 nM (pChEMBL 6.539999961853027)
Descriptors: MW 1126.29
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-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 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CC(C)O)C(=O)NCc1ccc(F)cc1)c1sccc1C
InChIKey: LJMHAKIVRBTXAJ-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 17782.79 nM (pChEMBL 4.75)
Descriptors: MW 500.71, ALogP 5.78, HBA 5, HBD 2, PSA 52.57, QED 0.35
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Inhibition of alphavbeta5 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 = 3002 nM (pChEMBL 5.519999980926514)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): O=C(O)C[C@@H](c1ccc(OCc2ccc3nc(-c4ccccc4)nn3c2)cc1)c1ccon1
InChIKey: KIZDOKWMTBVGAP-NRFANRHFSA-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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 440.46, ALogP 4.57, HBA 7, HBD 1, PSA 102.75, QED 0.38
Compound (SMILES): Cc1cc(Cl)cc(-c2cnc3ncn(-c4cc(O)cc(F)c4)c(=O)c3c2CN(C)C[C@@H]2CCCN2)c1
InChIKey: YBLBKTUFAZAQNI-FQEVSTJZSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Agonist activity at human SST5
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 508, ALogP 4.44, HBA 7, HBD 2, PSA 83.28, QED 0.4
Compound (SMILES): C=CC(=O)N1CC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)CC1
InChIKey: AYGSWHUBBRQXAY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Binding affinity to CDK13 (unknown origin) by TR-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 391.48, ALogP 3.23, HBA 4, HBD 2, PSA 90.98, QED 0.74
Compound (SMILES): c1ccc(-c2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: LDNVJIDFNXGSGT-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 337.38, ALogP 5.55, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Cc1cc(CN)cc(C)c1-c1ncn(C)c1-c1ccnc2cc(F)ccc12
InChIKey: WOAOENGFAAUUGT-UHFFFAOYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc in human MOLM-13 cells assessed as decrease in c-Myc protein expression level incubated for 24 hrs by HTRF assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 360.44, ALogP 4.52, HBA 4, HBD 1, PSA 56.73, QED 0.58
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27361
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl MAPK3
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): c1ccc(Cc2cncc3c2CC[C@@H]2CNCCN32)cc1
InChIKey: YEAATRDZIJRTNR-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Radioligand Binding Assay: Radioligand binding assays were performed using the commercially available 5-HT2 receptor agonist [125I]DOI as the radioligand and nonspecific binding was determined in the presence of unlabeled DOI at a saturating concentration of 10 μM. Competition experiments utilized 5-HT2 receptor expressing HEK293 cell membranes obtained as described in Example 3 (15-25 μg membrane protein/well) and radioligand at final assay concentrations of 0.4 to 0.6 nM. Experiments comprised addition of 95 μL of assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2), 50 μL of membranes, 50 μL of radioligand stock, and 5 μL of test compound diluted in assay buffer to 96-well microtiter plates, which were then incubated for 1 h at room temperature. Assay incubations were terminated by rapid filtration through PerkinElmer F/C filtration plates under reduced pressure using a 96-well Packard filtration apparatus, followed by washing three times with ice cold assay buffer. Plates were then dried at 45° C. for a minimum of 2 h. Finally, 25 μL of BetaScint scintillation cocktail was added to each well and the plates were counted in a Packard TopCount scintillation counter. In each competition study, test compounds were dosed at ten concentrations with triplicate determinations at each test concentration.
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 279.39, ALogP 2.4, HBA 3, HBD 1, PSA 28.16, QED 0.91