lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1noc(-c2c(N)ncnc2N[C@@H](C)c2nc3ccc(F)c(C#CCO)c3c(=O)n2-c2ccccc2)n1
InChIKey: RFVPQJHUNLIWKV-AWEZNQCLSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: PI3K (p110beta/p85alpha) (h) [Non-Radioactive Assay]: PI3K (p110β/p85α) (h) is incubated in assay buffer containing 10 μM phosphatidylinositol-4,5-bisphosphate and MgATP (concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 30 minutes at room temperature, the reaction is stopped by the addition of stop solution containing EDTA and biotinylated phosphatidylinositol-3,4,5-trisphosphate. Finally, detection buffer is added, which contains europium-labelled anti-GST monoclonal antibody, GST-tagged GRP1 PH domain and streptavidin-allophycocyanin. The plate is then read in timeresolved fluorescence mode and the homogenous time-resolved fluorescence (HTRF) signal is determined according to the formula HTRF=10000×(Em665 nm/Em620 nm).
Measurement: IC50 = 1596 nM (pChEMBL 5.800000190734863)
Descriptors: MW 512.51, ALogP 2.77, HBA 11, HBD 3, PSA 157.87, QED 0.3
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CC(F)C2)c2cc(-c3ccc(F)c(C(F)F)c3)cnc21
InChIKey: BMJMCYYKVKPQBO-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 408.36, ALogP 2.66, HBA 5, HBD 0, PSA 60.13, QED 0.62
Compound (SMILES): O=c1ccc(Cn2c(=O)[nH]c3ncc(-c4cccc(C(F)(F)F)c4)cc32)c[nH]1
InChIKey: FJJNJGQUPSRQFZ-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 1890 nM (pChEMBL 5.71999979019165)
Descriptors: MW 386.33, ALogP 3.15, HBA 4, HBD 2, PSA 83.54, QED 0.57
Compound (SMILES): FC(F)Oc1cc(-n2cc(COc3ncc(C(F)F)cn3)nn2)ccc1Cl
InChIKey: POXGNDTXJNUNKV-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: NMDA receptor FLIPR assay: NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 149 mM NaCl, 4 mM KCl, 2 mM CaCl2, and 1.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (149 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 2 mM CaCl2, 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to EC80 (standard assay) or EC40 (HTS assay) is used to maximize the assay's signal window or the ability to detect NMDA receptor antagonists and negative allosteric modulators, respectively. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 403.72, ALogP 3.83, HBA 7, HBD 0, PSA 74.95, QED 0.56
Compound (SMILES): COCc1cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n([C@@H]2CCC[C@@H]2C)c1=O
InChIKey: KQYUHJHGUAHQIZ-KBXCAEBGSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 0.54 nM (pChEMBL 9.270000457763672)
Descriptors: MW 449.58, ALogP 2.13, HBA 8, HBD 1, PSA 106.42, QED 0.72
Compound (SMILES): COC(C)(C)CNS(=O)(=O)N1CCC(Nc2ncc3cc(C)c(=O)n([C@@H]4CCC[C@@]4(C)O)c3n2)CC1
InChIKey: KVHQJEIOEXQVBK-NTKDMRAZSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 0.74 nM (pChEMBL 9.130000114440918)
Descriptors: MW 522.67, ALogP 1.71, HBA 9, HBD 3, PSA 138.68, QED 0.48
Compound (SMILES): Cc1cc(-c2nc(N[C@@H]3CCN(S(C)(=O)=O)C[C@H]3O)ncc2F)cc2c1nc(C)n2C(C)C
InChIKey: BAYGKMGZGJYXFQ-IEBWSBKVSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Biological Assay: CDK6/Cyclin D3: The purpose of the CDK6/Cyclin D3 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D3 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:1). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (±inhibitor), 2% glycerol, 10 mM MgCl2, 1 mM DTT, 3.5 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 4 nM (active sites) activated CDK6/Cyclin D3 in 40 mM HEPES buffer at pH 7.5.
Measurement: Ki = 17.6 nM (pChEMBL 7.75)
Descriptors: MW 476.58, ALogP 2.64, HBA 8, HBD 2, PSA 113.24, QED 0.58
Compound (SMILES): Cc1cnc(OCc2cn(-c3ccc(F)c(C)c3F)nn2)nc1N
InChIKey: ZURGRGNGWXNRHC-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: NMDA receptor FLIPR assay: NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 149 mM NaCl, 4 mM KCl, 2 mM CaCl2, and 1.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (149 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 2 mM CaCl2, 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to EC80 (standard assay) or EC40 (HTS assay) is used to maximize the assay's signal window or the ability to detect NMDA receptor antagonists and negative allosteric modulators, respectively. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 332.31, ALogP 2.11, HBA 7, HBD 1, PSA 91.74, QED 0.79
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CC(F)C2)c2cc(-c3ccc(F)c(F)c3)cnc21
InChIKey: WWNNHJQGPZMYAD-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 376.34, ALogP 1.86, HBA 5, HBD 0, PSA 60.13, QED 0.7
Compound (SMILES): C[C@]1(O)CCC[C@@H]1n1c(=O)ccc2cnc(NC3CCN(S(=O)(=O)NC4CCOCC4)CC3)nc21
InChIKey: PACLAQXDVXULPW-CVDCTZTESA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 22.2 nM (pChEMBL 7.650000095367432)
Descriptors: MW 506.63, ALogP 1.16, HBA 9, HBD 3, PSA 138.68, QED 0.53
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(N4CC(=O)NCC45CCCCC5)n3)nc2)CC1
InChIKey: WYBDIAZRTPZHAJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in CDK4/cyclinD1, CDK2/CycA and CDK2/cyclinE kinase assays to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology. The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Phosphoacceptor substrate peptide concentration used was 1 μM for all assays and Staurosporine was used as the reference compound for all assays. Specifics of each assay are as described below:CDK2/CyclinA: Enzyme concentration: 0.2 nM; ATP concentration: 50 μM; Incubation time: 3 hr.CDK2/CyclinE: Enzyme concentration: 0.28 nM; ATP concentration: 100 μM; Incubation time: 1 hr.CDK4/CyclinD1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 10 hr.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 436.56, ALogP 2.01, HBA 8, HBD 2, PSA 89.52, QED 0.75
Compound (SMILES): CCC(CC)CC(=O)NC(CCO[C@H]1C[C@H](CCc2ccc3c(n2)NCCC3)C1)C(=O)O
InChIKey: ATCTZVFUCRFDRM-NGZATLCBSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18564
Assay: Binding Assay: The biochemical potency of compounds was determined using a proximity-based assay (ALPHASCREEN®, Perkin Elmer, Waltham, Mass.) as described previously (Ullman E F et al., Luminescent oxygen channeling immunoassay: Measurement of particle binding kinetics by chemiluminescence. Proc. Natl. Acad. Sci. USA, Vol. 91, pp. 5426-5430, June 1994). To gauge the potency of inhibitors of binding to human integrin αvβ6, inhibitor compounds and integrin were incubated together with TGF-b1 LAP and biotinylated anti-LAP antibody plus acceptor and donor beads, following the manufacture's recommendations. The donor beads were coated with streptavidin. The acceptor beads had a nitrilotriacetic acid Ni chelator, for binding to a 6×His Tag on human integrin αvβ6. All incubations occurred at room temperatures in 50 mM Tris-HCl, pH 7.5, 0.1% BSA supplemented with 1 mM each CaCl2 and MgCl2.The order of reagent addition was as follows:1. Alpha-v-beta-6 integrin, test inhibitor compound, LAP, biotinylated anti-LAP antibody and acceptor beads were all added together.2. After 2 hours, donor beads were added. After another 30 minute incubation, samples were then read.Integrin binding was evaluated by exciting donor beads at 680 nm, and measuring the fluorescent signal produced, between 520-620 nm, using a Biotek Instruments (Winooski, Vt., USA) SynergyNeo2 multimode plate reader.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 445.6, ALogP 3.95, HBA 5, HBD 3, PSA 100.55, QED 0.42
Compound (SMILES): CC(O)C(C)Oc1cc(C(=O)N[C@H](C)c2ccc(C(F)(F)F)nc2)cc(-c2ncc(Cl)s2)c1
InChIKey: HTVWJAQZHONFAU-PNESKVBLSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Intracellular Calcium Measurement to Assess Antagonist Activity : A fluorescent imaging plate reader (FLEX/FLIPR station; Molecular Devices) was used to monitor intracellular calcium levels using the calcium-chelating dye Fluo-4 (Molecular Probes). The excitation and emission wavelengths used to monitor fluorescence were 470-495 nm and 515-575 nm, respectively. Cells expressing purinergic receptors P2X3 (human) or P2X2/3 (human) were plated at a density of 15,000 cells/well in collagen-coated 384-well plates approximately 20 hours before beginning the assay. On the day of the assay, 20 μl of loading buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, 2 μM Fluo-4, and 5 units/mL, hexokinase, pH=7.4) was added and cells dye-loaded for 90 min at 37° C. The dye supernatant was removed and replaced with 45 μl probenecid buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, pH=7.4). The test compound was added in a volume of 5 μl and allowed to incubate for 30 min at 37° C. The final assay DMSO concentration is 1%.The agonist, α,β-Me-ATP, was added in a volume of 20 μl at a concentration representing the EC80 value. The fluorescence was measured for an interval of 90 sec at 2 sec intervals and analyzed based on the increase in peak relative fluorescence units (RFU) compared to the basal fluorescence. Peak fluorescence was used to determine the response to agonist obtained at each concentration of test compound by the following equation: % Response=100*(RFU(test compound)−RFU(control))/(RFU(DMSO)−RFU(control)).
Measurement: IC50 = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 499.94, ALogP 5.52, HBA 6, HBD 2, PSA 84.34, QED 0.45
Compound (SMILES): Cc1noc(-c2c(N)ncnc2N[C@@H](C)c2nc3ccc(F)c(C#CCO)c3c(=O)n2-c2ccccc2)n1
InChIKey: RFVPQJHUNLIWKV-AWEZNQCLSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: PI3K (p110delta/p85alpha) (h) [Non-Radioactive Assay]: PI3K (p110δ/p85α) (h) is incubated in assay buffer containing 10 μM phosphatidylinositol-4, 5-bisphosphate and MgATP (concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 30 minutes at room temperature, the reaction is stopped by the addition of stop solution containing EDTA and biotinylated phosphatidylinositol-3,4,5-trisphosphate. Finally, detection buffer is added, which contains europium-labelled anti-GST monoclonal antibody, GST-tagged GRP1 PH domain and streptavidin-allophycocyanin. The plate is then read in timeresolved fluorescence mode and the homogenous time-resolved fluorescence (HTRF) signal is determined according to the formula HTRF=10000×(Em665 nm/Em620 nm).
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 512.51, ALogP 2.77, HBA 11, HBD 3, PSA 157.87, QED 0.3
Compound (SMILES): Cc1cnc(-c2cc(OC3CCOCC3)cc(C(=O)NC(C)c3ncc(Cl)cc3F)c2)s1
InChIKey: UXQVDYSQMZTJPS-UHFFFAOYSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Intracellular Calcium Measurement to Assess Antagonist Activity : A fluorescent imaging plate reader (FLEX/FLIPR station; Molecular Devices) was used to monitor intracellular calcium levels using the calcium-chelating dye Fluo-4 (Molecular Probes). The excitation and emission wavelengths used to monitor fluorescence were 470-495 nm and 515-575 nm, respectively. Cells expressing purinergic receptors P2X3 (human) or P2X2/3 (human) were plated at a density of 15,000 cells/well in collagen-coated 384-well plates approximately 20 hours before beginning the assay. On the day of the assay, 20 μl of loading buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, 2 μM Fluo-4, and 5 units/mL, hexokinase, pH=7.4) was added and cells dye-loaded for 90 min at 37° C. The dye supernatant was removed and replaced with 45 μl probenecid buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, pH=7.4). The test compound was added in a volume of 5 μl and allowed to incubate for 30 min at 37° C. The final assay DMSO concentration is 1%.The agonist, α,β-Me-ATP, was added in a volume of 20 μl at a concentration representing the EC80 value. The fluorescence was measured for an interval of 90 sec at 2 sec intervals and analyzed based on the increase in peak relative fluorescence units (RFU) compared to the basal fluorescence. Peak fluorescence was used to determine the response to agonist obtained at each concentration of test compound by the following equation: % Response=100*(RFU(test compound)−RFU(control))/(RFU(DMSO)−RFU(control)).
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 475.97, ALogP 5.35, HBA 6, HBD 1, PSA 73.34, QED 0.52
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(N4CC(=O)NCC45CCCCC5)n3)nc2)CC1
InChIKey: WYBDIAZRTPZHAJ-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in CDK4/cyclinD1, CDK2/CycA and CDK2/cyclinE kinase assays to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology. The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Phosphoacceptor substrate peptide concentration used was 1 μM for all assays and Staurosporine was used as the reference compound for all assays. Specifics of each assay are as described below:CDK2/CyclinA: Enzyme concentration: 0.2 nM; ATP concentration: 50 μM; Incubation time: 3 hr.CDK2/CyclinE: Enzyme concentration: 0.28 nM; ATP concentration: 100 μM; Incubation time: 1 hr.CDK4/CyclinD1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 10 hr.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 436.56, ALogP 2.01, HBA 8, HBD 2, PSA 89.52, QED 0.75
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(N4CC(=O)NCC45CCCCC5)n3)nc2)CC1
InChIKey: WYBDIAZRTPZHAJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in CDK4/cyclinD1, CDK2/CycA and CDK2/cyclinE kinase assays to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology. The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Phosphoacceptor substrate peptide concentration used was 1 μM for all assays and Staurosporine was used as the reference compound for all assays. Specifics of each assay are as described below:CDK2/CyclinA: Enzyme concentration: 0.2 nM; ATP concentration: 50 μM; Incubation time: 3 hr.CDK2/CyclinE: Enzyme concentration: 0.28 nM; ATP concentration: 100 μM; Incubation time: 1 hr.CDK4/CyclinD1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 10 hr.
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 436.56, ALogP 2.01, HBA 8, HBD 2, PSA 89.52, QED 0.75
Compound (SMILES): CC(O)C(C)Oc1cc(C(=O)N[C@H](C)c2ccc(C(F)(F)F)nc2)cc(-c2ncc(Cl)s2)c1
InChIKey: HTVWJAQZHONFAU-PNESKVBLSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Intracellular Calcium Measurement to Assess Antagonist Activity : A fluorescent imaging plate reader (FLEX/FLIPR station; Molecular Devices) was used to monitor intracellular calcium levels using the calcium-chelating dye Fluo-4 (Molecular Probes). The excitation and emission wavelengths used to monitor fluorescence were 470-495 nm and 515-575 nm, respectively. Cells expressing purinergic receptors P2X3 (human) or P2X2/3 (human) were plated at a density of 15,000 cells/well in collagen-coated 384-well plates approximately 20 hours before beginning the assay. On the day of the assay, 20 μl of loading buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, 2 μM Fluo-4, and 5 units/mL, hexokinase, pH=7.4) was added and cells dye-loaded for 90 min at 37° C. The dye supernatant was removed and replaced with 45 μl probenecid buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, pH=7.4). The test compound was added in a volume of 5 μl and allowed to incubate for 30 min at 37° C. The final assay DMSO concentration is 1%.The agonist, α,β-Me-ATP, was added in a volume of 20 μl at a concentration representing the EC80 value. The fluorescence was measured for an interval of 90 sec at 2 sec intervals and analyzed based on the increase in peak relative fluorescence units (RFU) compared to the basal fluorescence. Peak fluorescence was used to determine the response to agonist obtained at each concentration of test compound by the following equation: % Response=100*(RFU(test compound)−RFU(control))/(RFU(DMSO)−RFU(control)).
Measurement: IC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 499.94, ALogP 5.52, HBA 6, HBD 2, PSA 84.34, QED 0.45
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(N4CC(=O)NCC45CCCCC5)n3)nc2)CC1
InChIKey: WYBDIAZRTPZHAJ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in CDK4/cyclinD1, CDK2/CycA and CDK2/cyclinE kinase assays to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology. The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Phosphoacceptor substrate peptide concentration used was 1 μM for all assays and Staurosporine was used as the reference compound for all assays. Specifics of each assay are as described below:CDK2/CyclinA: Enzyme concentration: 0.2 nM; ATP concentration: 50 μM; Incubation time: 3 hr.CDK2/CyclinE: Enzyme concentration: 0.28 nM; ATP concentration: 100 μM; Incubation time: 1 hr.CDK4/CyclinD1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 10 hr.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 436.56, ALogP 2.01, HBA 8, HBD 2, PSA 89.52, QED 0.75
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(N4CC(=O)NCC45CCCCC5)n3)nc2)CC1
InChIKey: WYBDIAZRTPZHAJ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in CDK4/cyclinD1, CDK2/CycA and CDK2/cyclinE kinase assays to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology. The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Phosphoacceptor substrate peptide concentration used was 1 μM for all assays and Staurosporine was used as the reference compound for all assays. Specifics of each assay are as described below:CDK2/CyclinA: Enzyme concentration: 0.2 nM; ATP concentration: 50 μM; Incubation time: 3 hr.CDK2/CyclinE: Enzyme concentration: 0.28 nM; ATP concentration: 100 μM; Incubation time: 1 hr.CDK4/CyclinD1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 10 hr.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 436.56, ALogP 2.01, HBA 8, HBD 2, PSA 89.52, QED 0.75
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(N4CC(=O)NCC45CCCCC5)n3)nc2)CC1
InChIKey: WYBDIAZRTPZHAJ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in CDK4/cyclinD1, CDK2/CycA and CDK2/cyclinE kinase assays to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology. The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Phosphoacceptor substrate peptide concentration used was 1 μM for all assays and Staurosporine was used as the reference compound for all assays. Specifics of each assay are as described below:CDK2/CyclinA: Enzyme concentration: 0.2 nM; ATP concentration: 50 μM; Incubation time: 3 hr.CDK2/CyclinE: Enzyme concentration: 0.28 nM; ATP concentration: 100 μM; Incubation time: 1 hr.CDK4/CyclinD1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 10 hr.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 436.56, ALogP 2.01, HBA 8, HBD 2, PSA 89.52, QED 0.75
Compound (SMILES): O=C(Cc1cncc(NS(=O)(=O)C2CC2)n1)Nc1ccc(-c2cccnc2)cc1
InChIKey: BCIZUAWAMGBITH-UHFFFAOYSA-N
Target: CTP synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17812
Assay: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 409.47, ALogP 2.62, HBA 6, HBD 2, PSA 113.94, QED 0.62
Compound (SMILES): CN(CCOCCn1c2ccccc2c2ccccc21)C(CCO)C(=O)NCc1ccccc1Cl
InChIKey: KLLRNTLWDWNCCD-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 transfected in HEK293 cells assessed as reduction in [3H]-GABA uptake preincubated for 25 mins followed by [3H]-GABA addition and measured after 4 mins by liquid scintillation counting analysis
Measurement: IC50 = 23442.29 nM (pChEMBL 4.630000114440918)
Descriptors: MW 494.04, ALogP 4.46, HBA 5, HBD 2, PSA 66.73, QED 0.29
Compound (SMILES): CC(C)Nc1ccc(NS(=O)(=O)c2c(F)cccc2F)c(Nc2ccc3[nH]nnc3c2)n1
InChIKey: LJNHOTUDOMQQJJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of N-terminal GST-tagged/C-terminal 6His-tagged BRD4 BD1 (47 to 170 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using SGRGK(Ac)GGK(Ac)GLGK(Ac) GGAK(Ac)RHRK-biotinylated peptide as substrate incubated for 60 mins by alpha screen assay
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 459.48, ALogP 4, HBA 7, HBD 4, PSA 124.69, QED 0.33
Compound (SMILES): CC[C@@H](NC(=O)c1nn(-c2ccccc2)nc1N)c1ccc(C(=O)Nc2ccccc2N)cc1
InChIKey: FTFRRNJGOVWLPJ-HXUWFJFHSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 455.52, ALogP 3.57, HBA 7, HBD 4, PSA 140.95, QED 0.31
Compound (SMILES): C[C@@H]1CCCN1c1cc2c(c([C@H](N)CN)n1)CN(c1cccc(-c3nnc4n3[C@@H](C)CC4)n1)C2=O
InChIKey: AUOFLQBOFKWOGI-RVKKMQEKSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 (unknown origin)
Measurement: Ki < 0.05 nM (pChEMBL 10.300999641418457)
Descriptors: MW 473.59, ALogP 2.35, HBA 9, HBD 2, PSA 132.08, QED 0.58
Compound (SMILES): OC[C@H]1O[C@@H](n2nc3c4c(ncnc42)N(Cc2ccccc2)C=C3)[C@H](O)[C@@H]1O
InChIKey: RNZVYTHTQIRPKM-NVQRDWNXSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Inhibition of human 5-HT1D receptor assessed as inhibition constant by microbeta scintillation counting method
Measurement: Ki = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 381.39, ALogP 0.43, HBA 9, HBD 3, PSA 116.76, QED 0.6
Compound (SMILES): O=c1[nH]c(=O)n(COCc2ccccc2)c(Sc2ccccn2)c1C1CC1
InChIKey: PKIYEBXEYFYQNM-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild type HIV-1 reverse transcriptase assessed as inhibition of biotin deoxyuridine triphosphate incorporation into protein
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 381.46, ALogP 3.13, HBA 6, HBD 1, PSA 76.98, QED 0.64
Compound (SMILES): CCCN(CCC)C(=O)C1=Cc2ccc(-c3cccc(C(=O)CC)c3)cc2N=C(N)C1
InChIKey: FENOUMGWJKKCGA-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 (unknown origin)
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 417.55, ALogP 5.37, HBA 4, HBD 1, PSA 75.76, QED 0.59
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(-c4nnc(CN5C[C@@H](C)N[C@@H](C)C5)o4)cc3OC)nc2N1C1CCCC1
InChIKey: KWQBQLFHHAOBPA-SELNLUPBSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 575.72, ALogP 3.97, HBA 11, HBD 2, PSA 124.78, QED 0.41
Compound (SMILES): Cn1ncc2c(NC3CCC(F)(F)C3)nc(NC[C@H](N)c3ccccc3)nc21
InChIKey: JEHDDIUSETVYFV-WUJWULDRSA-N
Target: RNA 5'-monophosphate methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z5W3
Assay: Inhibition of BCDIN3D (unknown origin) using mini-helix and SAM as substrate incubated for 1 hr by RapidFire High Throughput mass spectrometry
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 387.44, ALogP 3.07, HBA 7, HBD 3, PSA 93.68, QED 0.6
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3c(OC4Cc5ccccc54)cc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: GWCBOLAEVUKUIO-UHFFFAOYSA-N
Target: DNA gyrase subunit B (SINGLE PROTEIN), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli full length wildtype GyrB24 (residue 1 to 220) supercoiling in presence of pNO1 plasmid incubated for 30 mins by microplate reader assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 488.35, ALogP 5.87, HBA 5, HBD 3, PSA 104.31, QED 0.33
Compound (SMILES): COc1cnc(Cl)cc1-c1cc(C)ncc1C(=O)Nc1nnc(O[C@H]2CC[C@H](O)C2)s1
InChIKey: FENLBOLPIJDBKQ-RYUDHWBXSA-N
Target: DNA polymerase theta (SINGLE PROTEIN), Homo sapiens
UniProt: O75417
Assay: Inhibition of human DNA polymerase theta (1 to 899 residues) ATPase activity using dT50 single strand DNA as substrate by NADH oxidation-coupled enzymatic assay
Measurement: IC50 <= 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 461.93, ALogP 3.51, HBA 9, HBD 2, PSA 119.35, QED 0.53
Compound (SMILES): C[C@H](NC(=O)Cn1nnc2sccc2c1=O)c1ccc(F)cc1
InChIKey: VVBFPKIGGIVZAU-VIFPVBQESA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis
Measurement: EC50 = 56.6 nM (pChEMBL 7.25)
Descriptors: MW 332.36, ALogP 1.87, HBA 6, HBD 1, PSA 76.88, QED 0.79
Compound (SMILES): CN1CCC(NC(=O)[C@H]2O[C@@H](n3ccc4c(N)ncnc43)[C@H](O)[C@@H]2O)CC1
InChIKey: YUYYBRXHXJDWSS-PFHKOEEOSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates incubated for 30 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 376.42, ALogP -1.16, HBA 9, HBD 4, PSA 138.76, QED 0.53
Compound (SMILES): C#C[C@H](CCSC)NC(=O)[C@@H]1[C@@H]2[C@H](CN1C(=O)[C@@H](NC(=O)C(F)(F)F)C(C)(C)C)C2(C)C
InChIKey: POKGOYUMQMREBP-OLMNGRFOSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of C-terminal recombinant SARS-CoV-2 main protease using ALNDFSNSGSDVLYQPPQTSITSAVLQ/SGFRKMAFPS-NH2 and AcSGFRXMAFPS-NH2 as substrate preincubated for 15 mins followed by substrate addition and measured for 30 mins by SPE-MS analysis
Measurement: IC50 = 11900 nM (pChEMBL 4.920000076293945)
Descriptors: MW 475.58, ALogP 2.43, HBA 4, HBD 2, PSA 78.51, QED 0.55
Compound (SMILES): Cc1nnc(N[C@H](C)c2cccc(C(F)(F)C(C)(C)O)c2)c2cc3c(cc12)n(C)c(=O)n3C1CC1
InChIKey: IGXFSCUDQOSJQK-CQSZACIVSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: P01116
Assay: Inhibition of N-terminal his 6-tagged human SOS1 (564 to 1049 residues)/ N-terminal GST tagged recombinant human wild type KRAS (1 to 188 residues) protein-protein interaction incubated for 60 mins by homogeneous time-resolved fluorescence assay
Measurement: IC50 = 7.413 nM (pChEMBL 8.130000114440918)
Descriptors: MW 481.55, ALogP 4.96, HBA 7, HBD 2, PSA 84.97, QED 0.41
Compound (SMILES): COc1cc(Nc2nc(NCC3(N)CC3)nc3c2cnn3C)cc(OC)c1
InChIKey: PDXXSIQLTJKFCD-UHFFFAOYSA-N
Target: RNA 5'-monophosphate methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z5W3
Assay: Inhibition of BCDIN3D (unknown origin) using mini-helix and SAM as substrate incubated for 1 hr by RapidFire High Throughput mass spectrometry
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 369.43, ALogP 2.03, HBA 9, HBD 3, PSA 112.14, QED 0.58
Compound (SMILES): O=C1CCC(N2C(=O)c3cccc(OCCCCn4cc(CCCCN5CCC(NC(=O)c6n[nH]cc6NC(=O)c6c(Cl)cccc6Cl)CC5)nn4)c3C2=O)C(=O)N1
InChIKey: RWZUENRHOXLKRD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) by luciferase reporter gene assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 833.73, ALogP 4.04, HBA 12, HBD 4, PSA 213.61, QED 0.09
Compound (SMILES): O=C(CCNC(=O)c1n[nH]cc1NC(=O)c1c(Cl)cccc1Cl)NO
InChIKey: XTXMSHSTABRIHN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) preincubated for 20 mins followed by [gamma-33P]ATP addition measured after 120 mins in presence of ATP by Hot-SpotSM kinase assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 386.2, ALogP 1.59, HBA 5, HBD 5, PSA 136.21, QED 0.38
Compound (SMILES): Cc1ncnc(C)c1-c1cccc(COc2ccc([S+]([O-])CC(=O)O)cc2)c1
InChIKey: ZXNDIKDYYGAEOU-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human GPR40 expressed in HEK293 cells by Fluo4-AM dye based intracellular calcium flux assay
Measurement: EC50 = 6518 nM (pChEMBL 5.190000057220459)
Descriptors: MW 396.47, ALogP 3.53, HBA 5, HBD 1, PSA 95.37, QED 0.61
Compound (SMILES): C=CC(=O)Nc1cc(-c2ccc([C@H](C)Nc3ncc(F)c(N4C(=O)OC[C@@H]4C(C)C)n3)cc2)ccc1N(C)C
InChIKey: UNWYJXHJZJFHBD-AVRWGWEMSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as NADPH consumption using alpha-KG as substrate measured after 60 mins
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 532.62, ALogP 5.63, HBA 7, HBD 2, PSA 99.69, QED 0.34
Compound (SMILES): COc1cc(-c2cc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C(F)(F)F)on4)cc3)n[nH]2)ccc1OCCN1CCOCC1
InChIKey: BYYJGNNQKMWKNN-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Binding affinity to RET (unknown origin) assessed as dissociation constant in presence of ATP by FRET based Z'-Lyte assay
Measurement: Kd = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 614.63, ALogP 5.94, HBA 8, HBD 3, PSA 126.77, QED 0.2
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(NC(=O)c4ccc(Cl)cc4)c4c3OCO4)c3c(N)ncnc32)C1
InChIKey: YGNFIFMHMKRCDL-QGZVFWFLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) preincubated for 10 mins followed by kinase substrate and ATP addition and measured for 20 mins by mobility shift assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 545.99, ALogP 4.06, HBA 9, HBD 2, PSA 137.49, QED 0.36
Compound (SMILES): Nc1nc(NC2=NC(c3ccccc3)=CC(c3ccccc3[N+](=O)[O-])O2)nc(N2CCOCC2)n1
InChIKey: CXFHDEBKXPLYTG-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human recombinant DPP-4 using H-GlyPro-AMC as substrate incubated for 10 mins by fluorescence based assay
Measurement: IC50 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 474.48, ALogP 2.78, HBA 11, HBD 2, PSA 153.92, QED 0.42
Compound (SMILES): COc1ccc(CC2CCN(C[C@](C)(O)[C@@H]3CC[C@@H](C)C[C@H]3O)CC2)cc1
InChIKey: SPMRZWPGKIGKPS-LUGPXAIHSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from guinea pig brain membrane sigma 1 receptor assessed as inhibition constant measured after 120 mins by scintillation counting method
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 375.55, ALogP 3.5, HBA 4, HBD 2, PSA 52.93, QED 0.8
Compound (SMILES): Cc1cc(C)c2c(n1)sc1c(Sc3nnc(-c4ccncc4)o3)ncnc12
InChIKey: PEHWQUMDGURJNJ-UHFFFAOYSA-N
Target: Toll-like receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O60602
Assay: Antagonist activity at TLR5 (unknown origin)
Measurement: IC50 = 50500 nM (pChEMBL 4.300000190734863)
Descriptors: MW 392.47, ALogP 4.45, HBA 9, HBD 0, PSA 90.48, QED 0.42
Compound (SMILES): CCCN(CCCc1ccccc1)Cc1ccc2ccccc2c1
InChIKey: YNZZDLPGQNWRQR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum BuChE using butyrylthiocholine iodide as substrate measured for 3 mins by Ellman's method
Measurement: IC50 = 1450 nM (pChEMBL 5.840000152587891)
Descriptors: MW 317.48, ALogP 5.68, HBA 1, HBD 0, PSA 3.24, QED 0.52
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@H](C=O)CCC(N)=O
InChIKey: DZTRNZUCEHMCEH-HOTGVXAUSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant hexa-His tagged SARS-COV2 main protease expressed in Escherichia coli using Dabcyl-KTSAVLQISGFRKM-E(Edans)-NH2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 377.44, ALogP 1.28, HBA 5, HBD 3, PSA 127.59, QED 0.5
Compound (SMILES): COc1cc2c(C(=O)N3CCC(F)CC3)cn(-c3ccc4scc(C)c4c3)c(=O)c2cc1OC
InChIKey: HELXFZDNFAKTSS-UHFFFAOYSA-N
Target: Lysophosphatidic acid receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H1C0
Assay: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 480.56, ALogP 5.11, HBA 6, HBD 0, PSA 60.77, QED 0.41