lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)/C=C/CN(C)C)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SURRDPSGERGIIM-VOTSOKGWSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 (875 to end residues) using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 459.6, ALogP 3.98, HBA 7, HBD 1, PSA 79.18, QED 0.54
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(C)(C)F
InChIKey: RMHSPVDIAHEXNT-NSYGIPOTSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 468.6, ALogP 4.5, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): O=C(Nc1cnn(-c2csc(C(=O)NC3COC3)c2)c1)Nc1ccccc1Cl
InChIKey: FPVKFPPNOMNINZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at -80 mV holding potential by automated Qpatch electrophysiological method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 417.88, ALogP 3.36, HBA 6, HBD 3, PSA 97.28, QED 0.59
Compound (SMILES): COc1cc2nc3ccccc3c(Nc3ccc(C(=O)NO)cc3)c2c(OC)c1OC
InChIKey: RXYDUXPNMOBQTR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human C-terminal 6His-tagged AChE (Glu32 to Leu614 residues) expressed in CHO cells using acetylthiocholine iodide as substrate preincubated for 5 mins measured after 15 mins by DTNB reagent based assay
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 419.44, ALogP 4.28, HBA 7, HBD 3, PSA 101.94, QED 0.24
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3cccnc3)CC2)cc1.O=C(O)C(=O)O
InChIKey: RADSTKUIYGICJB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5HT2A receptor by liquid scintillation counting
Measurement: Ki = 338 nM (pChEMBL 6.46999979019165)
Descriptors: MW 313.42, ALogP 3.37, HBA 3, HBD 0, PSA 19.37, QED 0.76
Compound (SMILES): Cc1cc(NC2CCc3ccc(Br)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: WSMWEZWUWJDREU-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp electrophysiology assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNC(=O)c3cccc(S(N)(=O)=O)c3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: BQYCUVSPDUOPHX-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 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 572.61, ALogP 1.54, HBA 10, HBD 4, PSA 196.57, QED 0.21
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: IBDOGMBSQPMZKN-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1R expressed in CHO cell membranes after 90 mins by [35S]GTPgammaS assay
Measurement: EC50 = 56.15 nM (pChEMBL 7.25)
Descriptors: MW 435.34, ALogP 4.56, HBA 3, HBD 1, PSA 51.1, QED 0.72
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)C(=O)N1CC[C@H](c2ccnc3ccc(F)cc23)[C@@H](O)C1
InChIKey: GZSMNWZYUMDTHO-XLIONFOSSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO in HEK cells
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 427.86, ALogP 3.34, HBA 4, HBD 2, PSA 82.53, QED 0.61
Compound (SMILES): Nc1cc(Cc2ccccc2)c2nn[nH]c2n1
InChIKey: SGFFXIGIHATQNC-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 225.25, ALogP 1.53, HBA 4, HBD 2, PSA 80.48, QED 0.69
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@@H](C)Cc1c(C)cc(O)cc1C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: ILKPOIXWHKKYRB-NJFSYGJFSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Antagonist activity at human KOR expressed in CHO cell membranes assessed as reduction in U50,488 induced response incubated for 1 hr by liquid scintillation counting based [35S]GTP-gamma-S assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 1232.54
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1
InChIKey: JTIFUJUJDWUQEV-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin) in presence of 5 mM ATP
Measurement: IC50 = 2780 nM (pChEMBL 5.559999942779541)
Descriptors: MW 413.5, ALogP 3.3, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ncccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: YFKOUTGKKFPEOH-QGZVFWFLSA-N
Target: Organic anion transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TCC7
Assay: Inhibition of OAT3 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4ccc5c(cnn5C)c4)cc3c2)cn1
InChIKey: ZUUIIFQSDQMWET-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 = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 382.43, ALogP 3.77, HBA 6, HBD 1, PSA 77.63, QED 0.52
Compound (SMILES): CNC(=O)c1cncc(-c2cnc(Cl)c(NS(=O)(=O)c3ccccc3)c2)c1
InChIKey: IHWSJFBJORCEAK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P42356
Assay: Inhibition of human PI4K3alpha by ADP-Glo kinase assay
Measurement: IC50 = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 402.86, ALogP 2.96, HBA 5, HBD 2, PSA 101.05, QED 0.64
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(=O)n(Cc4ccccc4F)c3)ccc12
InChIKey: DUHHTOOYELYHTE-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: ATP-competitive inhibition of recombinant human full-length N-terminal GST-fused MNK1 (1 to 424 residues) expressed in baculovirus expression system using GRSRSRSRSR as substrate and varying levels of ATP by ADP-glo luminescence assay
Measurement: Ki = 13.6 nM (pChEMBL 7.869999885559082)
Descriptors: MW 334.35, ALogP 3.16, HBA 4, HBD 2, PSA 76.7, QED 0.6
Compound (SMILES): CC(=O)Nc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: UCWSDAHSOCIBPK-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) 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 soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. 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 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 482.38, ALogP 4.56, HBA 4, HBD 2, PSA 70.67, QED 0.54
Compound (SMILES): CCC1CCCN(c2nc3ccc(Br)cc3c(C(=O)NCC(CCC(=O)O)c3ccccc3Cl)c2C)C1
InChIKey: ZJUNBYODVQMUCZ-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 586.96, ALogP 6.96, HBA 4, HBD 2, PSA 82.53, QED 0.28
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N[C@@H]3CCc4ccccc43)no2)cc1O
InChIKey: IXWUILRSNIQHDM-QGZVFWFLSA-N
Target: YEATS domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULM3
Assay: Selectivity interaction (Enzyme panel (PDEs, ion channels, and GPCRS, HTRF assay)) EUB0000731a YEATS2
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 391.43, ALogP 3.17, HBA 5, HBD 2, PSA 95.67, QED 0.71
Compound (SMILES): COCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: ZJPSQGKCYKMKSJ-VOQZNFBZSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Binding Assay: Membranes were prepared from CHO cells expressing human S1P1. Cells pellets (1x10^9 cells/pellet) were suspended in buffer containing 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), pH 7.5, 50 mM NaCl, 2 mM EDTA (Ethylenediaminetetraacetic acid) and Protease Inhibitor cocktail (Roche), and disrupted on ice using the Polytron homogenizer. The homogenate was centrifuged at 20,000 rpm (48,000 g) and the supernatant was discarded. The membrane pellets were resuspended in buffer containing 50 mM HEPES, pH 7.5, 100 mM NaCl, 1 mM MgCl2, 2 mM EDTA and stored in aliquots at -80Â° C. after protein concentration determination.Membranes (2 ug/well) and 0.03 nM final concentration of 33P-S1P ligand (1 mCi/ml, Perkin elmer or American Radiolabeled Chemicals) diluted in assay buffer (50 mM HEPES, pH7.4, 5 mM MgCl2, 1 mM CaCl2, 0.5% fatty acid free BSA (bovine serum albumin), 1 mM NaF) were added to the compound plates (384 Falcon v-bottom plate (0.5 ul/well in a 11 point, 3-fold dilution). Binding was performed for 45 minutes at room temperature, terminated by collecting the membranes onto 384-well Millipore FB filter plates, and radioactivity was measured by TOPCOUNT. The competition data of the test compounds over a range of concentrations was plotted as percentage inhibition of radioligand specific binding. The IC50 is defined as the concentration of competing ligand needed to reduce specific binding by 50%.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 425.51, ALogP 4.07, HBA 4, HBD 3, PSA 102.01, QED 0.39
Compound (SMILES): COc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: ZBGMKBKMVOGMLL-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28647
Assay: Displacement of [3H]NECA from rat adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki = 973 nM (pChEMBL 6.010000228881836)
Descriptors: MW 520.57, ALogP 6.03, HBA 8, HBD 1, PSA 99.25, QED 0.29
Compound (SMILES): COc1cc(-c2cn([C@H]3CCc4ccccc4N(CC(F)(F)F)C3=O)nn2)ccc1-n1ccc(C)n1
InChIKey: LMWVEVSLAFDIRE-QFIPXVFZSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 741.31 nM (pChEMBL 6.130000114440918)
Descriptors: MW 496.49, ALogP 4.53, HBA 7, HBD 0, PSA 78.07, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Inhibition of recombinant human N-terminal GST-tagged TXK (260 to 527 residues) expressed in baculovirus expression system using tyrosine-6 peptide as substrate preincubated for 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 = 294 nM (pChEMBL 6.53000020980835)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17B (SINGLE PROTEIN), Homo sapiens
UniProt: O94768
Assay: Inhibition of human STK17B in presence of ATP at Km level
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2c1CCO2
InChIKey: WGICPLUIQIXVNT-XQKZEKTMSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C INI receptor expressed in human HEK293 cells assessed as induction of beta-arrestin-2 recruitment incubated for 20 hrs by Tango assay
Measurement: EC50 = 318 nM (pChEMBL 6.5)
Descriptors: MW 251.3, ALogP 2.03, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@@H]1CCOC[C@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: WTHILFAMRXZBRN-SKBVVQJISA-N
Target: G protein-coupled receptor 34a (SINGLE PROTEIN), Danio rerio
UniProt: Q6XCC7
Assay: Agonist activity at zebrafish GPR34 type a expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 512.86 nM (pChEMBL 6.289999961853027)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)C4)c(Cl)cn2)C1
InChIKey: KZJSUGHOGMRTFQ-JQXSQYPDSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 415.93, ALogP 3.42, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cnccn2)CC1
InChIKey: PCQQITDIAVWGLB-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) 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 soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. 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 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 410.85, ALogP 2.88, HBA 5, HBD 1, PSA 67.35, QED 0.71
Compound (SMILES): CC(C)n1nc2c(c1-c1ccc(F)cc1)CCNCC2
InChIKey: RBYJHELKTYHZNG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 273.36, ALogP 2.96, HBA 3, HBD 1, PSA 29.85, QED 0.91
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)/C=C/CN(C)C)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SURRDPSGERGIIM-VOTSOKGWSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant human FLT3 D835Y mutant (564 to end residues) using EAIYAAPFAKKK as substrate at 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 459.6, ALogP 3.98, HBA 7, HBD 1, PSA 79.18, QED 0.54
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(C)(C)F
InChIKey: RMHSPVDIAHEXNT-NSYGIPOTSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 468.6, ALogP 4.5, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3cccnc3)CC2)cc1.O=C(O)C(=O)O
InChIKey: RADSTKUIYGICJB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5HT2A receptor by liquid scintillation counting
Measurement: Ki = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 313.42, ALogP 3.37, HBA 3, HBD 0, PSA 19.37, QED 0.76
Compound (SMILES): Cc1cc(NC2CCc3ccc(Br)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: WSMWEZWUWJDREU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using isoform-specific probe substrate in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNC(=O)c3cccc(S(N)(=O)=O)c3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: BQYCUVSPDUOPHX-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 572.61, ALogP 1.54, HBA 10, HBD 4, PSA 196.57, QED 0.21
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: IBDOGMBSQPMZKN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2R expressed in CHO cell membranes after 90 mins by [35S]GTPgammaS assay
Measurement: EC50 = 11.63 nM (pChEMBL 7.929999828338623)
Descriptors: MW 435.34, ALogP 4.56, HBA 3, HBD 1, PSA 51.1, QED 0.72
Compound (SMILES): Nc1cc(Cc2ccccc2)c2nn[nH]c2n1
InChIKey: SGFFXIGIHATQNC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 225.25, ALogP 1.53, HBA 4, HBD 2, PSA 80.48, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1
InChIKey: JTIFUJUJDWUQEV-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin) in presence of 5 mM ATP
Measurement: IC50 = 334 nM (pChEMBL 6.480000019073486)
Descriptors: MW 413.5, ALogP 3.3, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ncccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: YFKOUTGKKFPEOH-QGZVFWFLSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): CNC(=O)c1cncc(-c2cnc(Cl)c(NS(=O)(=O)c3ccccc3)c2)c1
InChIKey: IHWSJFBJORCEAK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Inhibition of human PI4K3beta by ADP-Glo kinase assay
Measurement: IC50 = 433 nM (pChEMBL 6.360000133514404)
Descriptors: MW 402.86, ALogP 2.96, HBA 5, HBD 2, PSA 101.05, QED 0.64
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(=O)n(Cc4ccccc4F)c3)ccc12
InChIKey: DUHHTOOYELYHTE-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: ATP-competitive inhibition of recombinant human full-length N-terminal GST-fused MNK2 (1 to 465 residues) expressed in baculovirus expression system using GRSRSRSRSR as substrate and varying levels of ATP by ADP-glo luminescence assay
Measurement: Ki = 11.1 nM (pChEMBL 7.960000038146973)
Descriptors: MW 334.35, ALogP 3.16, HBA 4, HBD 2, PSA 76.7, QED 0.6
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N[C@@H]3CCc4ccccc43)no2)cc1O
InChIKey: IXWUILRSNIQHDM-QGZVFWFLSA-N
Target: YEATS domain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95619
Assay: Selectivity interaction (Enzyme panel (PDEs, ion channels, and GPCRS, HTRF assay)) EUB0000731a YEATS4
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 391.43, ALogP 3.17, HBA 5, HBD 2, PSA 95.67, QED 0.71
Compound (SMILES): COCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: ZJPSQGKCYKMKSJ-VOQZNFBZSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: [35S] GTPgammaS Binding Assays: Compounds were loaded in a 384 Falcon v-bottom plate (0.5 ul/well in a 11 point, 3-fold dilution). Membranes prepared from S1P1/CHO cells or EDG3-Gal5-bla HEK293T cells (EDG3 equivalent S1P3) were added to the compound plate (40 ul/well, final protein 3 ug/well) with MULTIDROP. [35S] GTP (1250 Ci/mmol, Perkin Elmer) was diluted in assay buffer: 20 mM HEPES, pH7.5, 10 mM MgCl2, 150 mM NaCl, 1 mM EGTA (ethylene glycol tetraacetic acid), 1 mM DTT (Dithiothreitol), 10 uM GDP, 0.1% fatty acid free BSA, and 10 ug/ml Saponin to 0.4 nM. 40 ul of the [35S] GTP solution was added to the compound plate with a final concentration of 0.2 nM. The reaction was kept at room temperature for 45 min. At the end of incubation, all the mixtures in the compound plate were transferred to Millipore 384-well FB filter plates via the VELOCITY11 Vprep liquid handler. The filter plate was washed with water 4 times by using the manifold Embla plate washer and dried at 60° C. for 45 min. MicroScint 20 scintillation fluid (30 ul) was added to each well for counting on the Packard TOPCOUNT. EC50 is defined as the agonist concentration that corresponds to 50% of the Ymax (maximal response) obtained for each individual compound tested.
Measurement: EC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 425.51, ALogP 4.07, HBA 4, HBD 3, PSA 102.01, QED 0.39
Compound (SMILES): COc1cc(-c2cn([C@H]3CCc4ccccc4N(CC(F)(F)F)C3=O)nn2)ccc1-n1ccc(C)n1
InChIKey: LMWVEVSLAFDIRE-QFIPXVFZSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: GPCRScan assay: inhibition of SERT
Measurement: Ki = 390.58 nM (pChEMBL 6.409999847412109)
Descriptors: MW 496.49, ALogP 4.53, HBA 7, HBD 0, PSA 78.07, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of His-tagged human recombinant ERBB2 (676 to 1255 residues) expressed in baculovirus expression system using Tyr 06 as substrate preincubated for 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RR4
Assay: Inhibition of human CAMKK2 in presence of ATP at Km level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2c1CCO2
InChIKey: WGICPLUIQIXVNT-XQKZEKTMSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Agonist activity at MT1 (unknown origin) expressed in HEK293T cells incubated for 15 mins by melatonin Gi/o-mediated cAMP inhibition GloSensor assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 251.3, ALogP 2.03, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@@H]1CCOC[C@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: WTHILFAMRXZBRN-SKBVVQJISA-N
Target: G protein-coupled receptor 34b (SINGLE PROTEIN), Danio rerio
UniProt: B0S6P9
Assay: Agonist activity at zebrafish GPR34 type b expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): CC(C)n1nc2c(c1-c1ccc(F)cc1)CCNCC2
InChIKey: RBYJHELKTYHZNG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 273.36, ALogP 2.96, HBA 3, HBD 1, PSA 29.85, QED 0.91
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)/C=C/CN(C)C)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SURRDPSGERGIIM-VOTSOKGWSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 V617F mutant in human SET2 cells
Measurement: IC50 = 475.3 nM (pChEMBL 6.320000171661377)
Descriptors: MW 459.6, ALogP 3.98, HBA 7, HBD 1, PSA 79.18, QED 0.54
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3cccnc3)CC2)cc1.O=C(O)C(=O)O
InChIKey: RADSTKUIYGICJB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5HT7 receptor by liquid scintillation counting
Measurement: Ki = 267 nM (pChEMBL 6.570000171661377)
Descriptors: MW 313.42, ALogP 3.37, HBA 3, HBD 0, PSA 19.37, QED 0.76
Compound (SMILES): Cc1cc(NC2CCc3ccc(Br)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: WSMWEZWUWJDREU-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes using isoform-specific probe substrates in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: IBDOGMBSQPMZKN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO-K1 cells assessed as inhibition of froskolin-stimulated cAMP accumulation incubated for 90 mins by HitHunter chemiluminescence based assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 435.34, ALogP 4.56, HBA 3, HBD 1, PSA 51.1, QED 0.72
Compound (SMILES): Nc1cc(Cc2ccccc2)c2nn[nH]c2n1
InChIKey: SGFFXIGIHATQNC-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 225.25, ALogP 1.53, HBA 4, HBD 2, PSA 80.48, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1
InChIKey: JTIFUJUJDWUQEV-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00526
Assay: Inhibition of CDK3 (unknown origin) in presence of 5 mM ATP
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 413.5, ALogP 3.3, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ncccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: YFKOUTGKKFPEOH-QGZVFWFLSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Inhibition of OATP1B1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): COCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: ZJPSQGKCYKMKSJ-VOQZNFBZSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: [35S] GTPgammaS Binding Assays: Compounds were loaded in a 384 Falcon v-bottom plate (0.5 ul/well in a 11 point, 3-fold dilution). Membranes prepared from S1P1/CHO cells or EDG3-Gal5-bla HEK293T cells (EDG3 equivalent S1P3) were added to the compound plate (40 ul/well, final protein 3 ug/well) with MULTIDROP. [35S] GTP (1250 Ci/mmol, Perkin Elmer) was diluted in assay buffer: 20 mM HEPES, pH7.5, 10 mM MgCl2, 150 mM NaCl, 1 mM EGTA (ethylene glycol tetraacetic acid), 1 mM DTT (Dithiothreitol), 10 uM GDP, 0.1% fatty acid free BSA, and 10 ug/ml Saponin to 0.4 nM. 40 ul of the [35S] GTP solution was added to the compound plate with a final concentration of 0.2 nM. The reaction was kept at room temperature for 45 min. At the end of incubation, all the mixtures in the compound plate were transferred to Millipore 384-well FB filter plates via the VELOCITY11 Vprep liquid handler. The filter plate was washed with water 4 times by using the manifold Embla plate washer and dried at 60° C. for 45 min. MicroScint 20 scintillation fluid (30 ul) was added to each well for counting on the Packard TOPCOUNT. EC50 is defined as the agonist concentration that corresponds to 50% of the Ymax (maximal response) obtained for each individual compound tested.
Measurement: EC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 425.51, ALogP 4.07, HBA 4, HBD 3, PSA 102.01, QED 0.39
Compound (SMILES): COc1cc(-c2cn([C@H]3CCc4ccccc4N(CC(F)(F)F)C3=O)nn2)ccc1-n1ccc(C)n1
InChIKey: LMWVEVSLAFDIRE-QFIPXVFZSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: GPCRScan assay: inhibition of SERT
Measurement: Ki = 380.19 nM (pChEMBL 6.420000076293945)
Descriptors: MW 496.49, ALogP 4.53, HBA 7, HBD 0, PSA 78.07, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of recombinant human N-terminal GST-tagged ERBB4 catalytic domain (708 to 993 residues) expressed in baculovirus expression system using tyrosine-1 peptide as substrate preincubated for 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human AURKB in presence of ATP at Km level
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2c1CCO2
InChIKey: WGICPLUIQIXVNT-XQKZEKTMSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at MT2(unknown origin) expressed in HEK293T cells incubated for 15 mins by melatonin Gi/o-mediated cAMP inhibition GloSensor assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 251.3, ALogP 2.03, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@@H]1CCOC[C@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: WTHILFAMRXZBRN-SKBVVQJISA-N
Target: G protein-coupled receptor 34b (SINGLE PROTEIN), Danio rerio
UniProt: B0S6P9
Assay: Agonist activity at zebrafish GPR34 type b expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 11.48 nM (pChEMBL 7.940000057220459)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)C4)c(Cl)cn2)C1
InChIKey: KZJSUGHOGMRTFQ-JQXSQYPDSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 415.93, ALogP 3.42, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3cccnc3)CC2)cc1.O=C(O)C(=O)O
InChIKey: RADSTKUIYGICJB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5HT7 receptor by liquid scintillation counting
Measurement: Ki = 234.42 nM (pChEMBL 6.630000114440918)
Descriptors: MW 313.42, ALogP 3.37, HBA 3, HBD 0, PSA 19.37, QED 0.76
Compound (SMILES): Cc1cc(NC2CCc3ccc(Br)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: WSMWEZWUWJDREU-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using isoform-specific probe substrates in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 = 16900 nM (pChEMBL 4.769999980926514)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: IBDOGMBSQPMZKN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO-K1 cells assessed as enhancement of beta arrestin-2 recruitment incubated for 90 mins by HitHunter chemiluminescence based assay
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 435.34, ALogP 4.56, HBA 3, HBD 1, PSA 51.1, QED 0.72
Compound (SMILES): Nc1cc(Cc2ccccc2)c2nn[nH]c2n1
InChIKey: SGFFXIGIHATQNC-UHFFFAOYSA-N
Target: Eosinophil peroxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P11678
Assay: Inhibition of human EPX bromination activity using tyrosine as substrate by measuring 3-bromo tyrosine formation incubated for 10 mins
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 225.25, ALogP 1.53, HBA 4, HBD 2, PSA 80.48, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1
InChIKey: JTIFUJUJDWUQEV-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of recombinant full length human CDK2/CyclinE expressed in insect cells using FL-Ahx-QSPKKG-CONH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 413.5, ALogP 3.3, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): COc1cc(-c2cn([C@H]3CCc4ccccc4N(CC(F)(F)F)C3=O)nn2)ccc1-n1ccc(C)n1
InChIKey: LMWVEVSLAFDIRE-QFIPXVFZSA-N
Target: Presenilin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49768
Assay: Affinity Phenotypic Cellular interaction (Abeta42 inhibition assay (electrochemiluminescent detection of peptides secreted by SH-SY5Y cells stably overexpressing the APP C-terminal fragment SPA4CT)) EUB0000739a PSEN1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 496.49, ALogP 4.53, HBA 7, HBD 0, PSA 78.07, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 catalytic domain (781 to 1124 residues) expressed in baculovirus expression system using tyrosine-6 peptide as substrate preincubated for 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 = 838 nM (pChEMBL 6.079999923706055)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N5S9
Assay: Inhibition of human CAMKK1 in presence of ATP at Km level
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): Cc1cc(NC2CCc3ccc(Br)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: WSMWEZWUWJDREU-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using isoform-specific probe substrates in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: IBDOGMBSQPMZKN-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP55,940 from human CB1R expressed in CHO-K1 cell membranes assessed as inhibition constant incubated for 2 hrs by liquid scintillation spectrometry analysis
Measurement: Ki = 0.79 nM (pChEMBL 9.100000381469727)
Descriptors: MW 435.34, ALogP 4.56, HBA 3, HBD 1, PSA 51.1, QED 0.72
Compound (SMILES): Nc1cc(Cc2ccccc2)c2nn[nH]c2n1
InChIKey: SGFFXIGIHATQNC-UHFFFAOYSA-N
Target: Thyroid peroxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P07202
Assay: Inhibition of TPO (unknown origin) using 3-iodo tyrosine as substrate incubated for 10 mins
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 225.25, ALogP 1.53, HBA 4, HBD 2, PSA 80.48, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1
InChIKey: JTIFUJUJDWUQEV-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of recombinant full length human His-tagged CDK1/CyclinB expressed in baculovirus infected insect cells using 5FAM-RRRFRPASPLRGPPKCOOH as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 413.5, ALogP 3.3, HBA 5, HBD 2, PSA 88.91, QED 0.8