lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-UWELNFAVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(I)c(Nc3ccccc3P(C)(C)=O)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: BPGJJKMCXBBEBI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/L858R double mutant (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Measurement: EC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 663.5, ALogP 4.95, HBA 9, HBD 3, PSA 111.72, QED 0.14
Compound (SMILES): C/C1=C\C[C@H](O)/C(C)=C/[C@H]2OC(=O)[C@@H](C)C2CC1
InChIKey: RLHPCSSGTQNSJN-YMHQTZQXSA-N
Target: Taste receptor type 2 member 31 (SINGLE PROTEIN), Homo sapiens
UniProt: P59538
Assay: Agonist activity at recombinant human N-terminal rat ST3 receptor-fused TAS2R44 expressed in HEK293T cells co-expressing Galpha16gust44 assessed as effect on intracellular calcium level by FLIPR assay
Measurement: EC50 = 31500 nM (pChEMBL 4.5)
Descriptors: MW 250.34, ALogP 2.6, HBA 3, HBD 1, PSA 46.53, QED 0.53
Compound (SMILES): COC(=O)N1CCN([C@H]2CC[C@H](Nc3nc(Nc4cnn(C)c4)nc4ccc(CC#N)nc34)CC2)CC1
InChIKey: RPGMSHCJIWHISY-IRJFHVNHSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human recombinant CLK2 expressed in Baculovirus system
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 504.6, ALogP 2.68, HBA 11, HBD 2, PSA 137.12, QED 0.52
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin)
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1cc(F)ccc1F
InChIKey: KLWKJFRXLGLTIH-VIFPVBQESA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 524 nM (pChEMBL 6.28000020980835)
Descriptors: MW 447.89, ALogP 5.19, HBA 5, HBD 2, PSA 71.09, QED 0.55
Compound (SMILES): CC[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(CNc3ncc(C(=O)NO)cn3)c2c(=O)n1-c1ccccc1
InChIKey: WJOMMYWEPXHYNA-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 563.58, ALogP 3.14, HBA 12, HBD 5, PSA 188.52, QED 0.13
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-UWELNFAVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): C/C1=C\C[C@H](O)/C(C)=C/[C@H]2OC(=O)[C@@H](C)C2CC1
InChIKey: RLHPCSSGTQNSJN-YMHQTZQXSA-N
Target: Taste receptor type 2 member 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYW0
Assay: Agonist activity at recombinant human N-terminal rat ST3 receptor-fused TAS2R10 expressed in HEK293T cells co-expressing Galpha16gust44 assessed as effect on intracellular calcium level by FLIPR assay
Measurement: EC50 = 25200 nM (pChEMBL 4.599999904632568)
Descriptors: MW 250.34, ALogP 2.6, HBA 3, HBD 1, PSA 46.53, QED 0.53
Compound (SMILES): COC(=O)N1CCN([C@H]2CC[C@H](Nc3nc(Nc4cnn(C)c4)nc4ccc(CC#N)nc34)CC2)CC1
InChIKey: RPGMSHCJIWHISY-IRJFHVNHSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) in presence of ATP by enzymatic assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 504.6, ALogP 2.68, HBA 11, HBD 2, PSA 137.12, QED 0.52
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human wild type RET
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-UWELNFAVSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): COC(=O)N1CCN([C@H]2CC[C@H](Nc3nc(Nc4cnn(C)c4)nc4ccc(CC#N)nc34)CC2)CC1
InChIKey: RPGMSHCJIWHISY-IRJFHVNHSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) phosphorylation by cell based assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 504.6, ALogP 2.68, HBA 11, HBD 2, PSA 137.12, QED 0.52
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human RET V804L mutant
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1cc(F)ccc1F
InChIKey: KLWKJFRXLGLTIH-VIFPVBQESA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 7682 nM (pChEMBL 5.119999885559082)
Descriptors: MW 447.89, ALogP 5.19, HBA 5, HBD 2, PSA 71.09, QED 0.55
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-UWELNFAVSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human RET V804M mutant
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Binding affinity to recombinant GST-tagged wild type human RET (658 to 1114 residues) extracted from insect cells incubated for 1 hrs by HTRF assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1cc(F)ccc1F
InChIKey: KLWKJFRXLGLTIH-VIFPVBQESA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 5115 nM (pChEMBL 5.289999961853027)
Descriptors: MW 447.89, ALogP 5.19, HBA 5, HBD 2, PSA 71.09, QED 0.55
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Binding affinity to GST/His-tagged recombinant human RET V804M mutant extracted from baculovirus incubated for 1 hrs by HTRF assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Binding affinity to N-terminal GST/His-tagged recombinant human RET G810R mutant extracted from Sf9 insect cells incubated for 1 hrs by HTRF assay
Measurement: IC50 = 207.3 nM (pChEMBL 6.679999828338623)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to CRBN (unknown origin) by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-RWYJCYHVSA-N
Target: Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of CCDC6-RET fusion protein in human LC2 cells assessed as inhibition of phospho-RET level measured after 30 mins
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): COc1ncc(-c2cc(OCC3CC3)c3ncnc(C)c3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: SMNLEJPURJQOPX-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal FLAG-tagged full-length p110alpha/human p85alpha expressed in Sf9 insect cells using PIP2 as substrate by kinase-glo assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 512.54, ALogP 4.88, HBA 7, HBD 1, PSA 103.3, QED 0.36
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(S(=O)(=O)N2CCC(NC(=O)c3n[nH]cc3NC(=O)c3c(Cl)cc(Cl)cc3Cl)CC2)c1
InChIKey: HZPYSAHDRSBARR-QPJJXVBHSA-N
Target: Cyclin-Y/Cyclin-dependent kinase 16 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00536
Assay: Competitive irreversible inhibition of CDK16/cyclin Y (unknown origin) in presence of Km ATP
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 683.02, ALogP 4.26, HBA 7, HBD 4, PSA 156.6, QED 0.23
Compound (SMILES): CCC(Nc1ccc(S(=O)(=O)Nc2nccs2)cc1Cl)c1ccccc1
InChIKey: SDPRTZGVTOHKRX-UHFFFAOYSA-N
Target: SCN8A/SCN1B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of recombinant human full length Nav1.6 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 407.95, ALogP 5.16, HBA 5, HBD 2, PSA 71.09, QED 0.57
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cn(Cc3cccc(N4CCOCC4)c3)c3ccc(F)cc23)[C@H](O)[C@@H]1O
InChIKey: OXOQCSFIVOZOEF-OIYQIAEKSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Inhibition of SAE (unknown origin) using recombinant His-tagged human SUMO1 measured after 2 hrs by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 640.69, ALogP 1.43, HBA 12, HBD 4, PSA 182.13, QED 0.18
Compound (SMILES): CCc1nnc(-c2cnc3ccc(-c4cnc(OC)c(NS(=O)(=O)c5ccc(F)cc5F)c4)cn23)o1
InChIKey: VAXGPSLDFLGGNF-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay
Measurement: IC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 512.5, ALogP 4.1, HBA 9, HBD 1, PSA 124.51, QED 0.35
Compound (SMILES): CCCNNC(=O)/C=C/c1ccc(CN(CCc2c(C)[nH]c3ccccc23)C(=O)OC(C)(C)C)cc1
InChIKey: RQNUUDSNIYAPPO-FOCLMDBBSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human C-terminal GST/His-tagged HDAC3 (1 to 428 residues) co-expressed with human N-terminal GST-tagged NCOR2 (395 to 489 residues) in baculovirus infected Sf9 cells using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based micro plate reader analysis
Measurement: IC50 = 16.76 nM (pChEMBL 7.78000020980835)
Descriptors: MW 490.65, ALogP 5.5, HBA 4, HBD 3, PSA 86.46, QED 0.2
Compound (SMILES): Cn1cc(Nc2ncc(F)c(N3C[C@H]4CC[C@H](C3)N4C(=O)C3CC3)n2)cn1
InChIKey: HGFHSGAVIGXYBV-ZIAGYGMSSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 signaling pathway in human lymphocytes of whole blood assessed as reduction in IFN-alpha induced STAT3 phosphorylation preincubated for 45 mins followed by IFN-alpha addition and measured measured after 15 mins by FACS assay
Measurement: IC50 = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 371.42, ALogP 1.68, HBA 7, HBD 1, PSA 79.18, QED 0.88
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1cc(F)ccc1F
InChIKey: KLWKJFRXLGLTIH-VIFPVBQESA-N
Target: SCN8A/SCN1B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of recombinant human full length Nav1.6 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay
Measurement: IC50 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 447.89, ALogP 5.19, HBA 5, HBD 2, PSA 71.09, QED 0.55
Compound (SMILES): CCNC(=O)Nc1cc(Nc2ccc(OC)cc2)c(C(=O)Nc2cccnc2)cn1
InChIKey: FSOAZMGZMXDGQX-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli DNA gyrase(A2B2 tetramer) preincubated for 5 mins followed by ATP addition and measured once per minute for 20 to 30 minutes by ATPase assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 406.45, ALogP 3.62, HBA 6, HBD 4, PSA 117.27, QED 0.48
Compound (SMILES): COc1cccc(-c2nc3c(N[C@@H]4C[C@@H](COS(N)(=O)=O)[C@@H](O)C4)ncnc3[nH]2)c1OC
InChIKey: IATMINVMLQNSTJ-LOWVWBTDSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAE using GST-tagged Ubc12 and Flag-tagged Nedd8 incubated for 105 mins by HTRF assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 464.5, ALogP 0.81, HBA 10, HBD 4, PSA 174.57, QED 0.37
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: PLUOMRKSSTXRGM-HSGJTTTCSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.026 nM (pChEMBL 10.59000015258789)
Descriptors: MW 3638.09
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccc(C(N)=O)cc1OC
InChIKey: PENFDVUMLLDOTA-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 in human Kit225 T cells assessed as inhibition of STAT phosphorylation by luciferase reporter assay
Measurement: IC50 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 410.41, ALogP 2.57, HBA 7, HBD 4, PSA 131.26, QED 0.47
Compound (SMILES): O=C(Nc1ccc(Cl)c(C(F)(F)F)c1)N[C@H]1CCN(c2ccnc(NC3CC3)n2)C1
InChIKey: WFJJLBVYQIIGHG-ZDUSSCGKSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Displacement of tracer236 from full-length His-tagged CDK8/cyclin C (unknown origin) incubated for 1 hr by TR-FRET analysis
Measurement: IC50 = 20.3 nM (pChEMBL 7.690000057220459)
Descriptors: MW 440.86, ALogP 4.12, HBA 5, HBD 3, PSA 82.18, QED 0.65
Compound (SMILES): O=C(c1cncc(N2CC3CC(C2)N3)c1)N1CCCc2ccccc21
InChIKey: XMYWPQXQUQJAEN-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Displacement of [3H]epibatidine from alpha4beta2 nAChR in rat cerebral cortex membrane
Measurement: Ki = 0.196 nM (pChEMBL 9.710000038146973)
Descriptors: MW 334.42, ALogP 2.23, HBA 4, HBD 1, PSA 48.47, QED 0.91
Compound (SMILES): COc1ccc(Nc2ncc3c(n2)CCC3)cc1
InChIKey: DZTRWURGVDMWQQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of recombinant full length N-terminal GST tagged human CDK5/p25 expressed in baculovirus infected sf9 cells using histone H1 as substrate measured after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 1720 nM (pChEMBL 5.760000228881836)
Descriptors: MW 241.29, ALogP 2.72, HBA 4, HBD 1, PSA 47.04, QED 0.9
Compound (SMILES): O=C1CCc2ccccc2N1CCCCN1CCN(C2CCCCC2)CC1
InChIKey: HZVGBWBVVRIGJW-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Displacement of [3H]ifenprodil from GluN1a/GluN2B (unknown origin) expressed in mouse L(tk-) cell membranes after 120 mins by solid scintillation counting method
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 369.55, ALogP 3.7, HBA 3, HBD 0, PSA 26.79, QED 0.72
Compound (SMILES): COc1ccc(N2C(=O)COc3ccc(-c4cnc5ccccc5c4)cc32)cc1
InChIKey: CELFRCHPJSSCQD-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PI3Kalpha (1 to 1068 residues)/PIK3R1 (1 to 724 residues) expressed in baculovirus expression system using PIP2 as substrate incubated for 1 hr by ADP-Glo assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.42, ALogP 4.97, HBA 4, HBD 0, PSA 51.66, QED 0.5
Compound (SMILES): CC(=O)N1CCN(c2nccc3c(-c4ccc5c(c4)CC(=O)N5)c(-c4ccc(F)cc4)nn23)CC1
InChIKey: UERCDXIHPYCAMF-UHFFFAOYSA-N
Target: GRIA1/CACNG2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P42261
Assay: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay
Measurement: IC50 = 0.2512 nM (pChEMBL 9.600000381469727)
Descriptors: MW 470.51, ALogP 3.37, HBA 6, HBD 1, PSA 82.84, QED 0.5
Compound (SMILES): O=C(CO[C@@H]1C[C@@H](CNc2ccccn2)N(C(=O)OCc2ccccc2)C1)NC[C@H](NC(=O)c1ccccc1-c1ccccc1)C(=O)O
InChIKey: MRGLCDMUTJGVNZ-QXIHQKPUSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Inhibition of fibronectin binding to human integrin alpha5beta1 extracellular domain incubated for 1 hr by competitive ELISA
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 651.72, ALogP 3.96, HBA 8, HBD 4, PSA 159.19, QED 0.16
Compound (SMILES): CCn1nccc1Nc1nc(-c2ccc(-n3cnc(C)c3)c(F)c2)cs1
InChIKey: QJVFENDDASKQHL-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 368.44, ALogP 4.4, HBA 7, HBD 1, PSA 60.56, QED 0.57
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cn(Cc3cccc(Br)c3)c3ccc(F)cc23)[C@H](O)[C@@H]1O
InChIKey: GEVVUAXCPLJANF-KSZWDZKGSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Inhibition of SAE (unknown origin) using recombinant His-tagged human SUMO1 measured after 2 hrs by HTRF assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 634.48, ALogP 2.35, HBA 10, HBD 4, PSA 169.66, QED 0.2
Compound (SMILES): CC(C)(C)CC(=O)Nc1nn2c(C(C)(C)C)ccnc2c1-c1ccc(OC(F)(F)F)cc1
InChIKey: SNKATGBJOXUFDQ-UHFFFAOYSA-N
Target: Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3) (PROTEIN COMPLEX), Homo sapiens
UniProt: O43526
Assay: Agonist activity at human KCNQ2/3 expressed in HEK293 cells by FLIPR based thallium influx assay
Measurement: EC50 > 32000 nM (pChEMBL 4.494999885559082)
Descriptors: MW 448.49, ALogP 5.97, HBA 5, HBD 1, PSA 68.52, QED 0.53
Compound (SMILES): N[C@@H]1[C@@H]2CC[C@@H](C2)[C@H]1c1ccc(Cl)nc1
InChIKey: NKHNTAYDCXZLFL-IZLWQMGWSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Agonist activity at human alpha3beta2 nAChR expressed in Xenopus laevis oocytes after 4 to 5 days at -60 mV holding potential by patch clamp assay
Measurement: EC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 222.72, ALogP 2.58, HBA 2, HBD 1, PSA 38.91, QED 0.74
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1cccc(C(N)=O)c1OC
InChIKey: SHFGZSHVGYQOFV-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 in human Kit225 T cells assessed as inhibition of STAT phosphorylation by luciferase reporter assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 410.41, ALogP 2.57, HBA 7, HBD 4, PSA 131.26, QED 0.47
Compound (SMILES): Cc1cc(C)c(S(=O)(=O)N[C@@H](CNC(=O)CO[C@@H]2C[C@@H](CNc3ccccn3)N(C(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)C2)C(=O)O)c(C)c1
InChIKey: KYNABGLMBKUXAX-ZCNNSNEGSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Inhibition of fibronectin binding to human integrin alpha5beta1 extracellular domain incubated for 1 hr by competitive ELISA
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 915.67, ALogP 5.33, HBA 8, HBD 4, PSA 167.03, QED 0.14
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCCCCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: FANPYQPRSROCKC-PCZBOVPISA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Antagonist activity at rat alpha3beta2 nACHR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 1693.98
Compound (SMILES): Cc1ccc(C(=O)N2CCc3sc(C(=O)NCC(O)CN4CCc5ccccc5C4)cc3C2)cc1
InChIKey: HHFHJTNECFJVEY-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues)/human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using H4 peptide as substrate preincubated for 15 mins followed by substrate and [3H]SAM addition and measured after 1 hr by scintillation counting method
Measurement: IC50 = 32.5 nM (pChEMBL 7.489999771118164)
Descriptors: MW 489.64, ALogP 3.4, HBA 5, HBD 2, PSA 72.88, QED 0.56
Compound (SMILES): Cc1ncnc2c1ccn2[C@@H]1O[C@H]([C@H](O)c2ccc(F)c(F)c2)[C@@H](O)[C@H]1O
InChIKey: UEAAYHPSDGGRQI-ORDFZIBCSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 377.35, ALogP 1.37, HBA 7, HBD 3, PSA 100.63, QED 0.64
Compound (SMILES): CC[C@H](Nc1ncnc2c1nc(-c1cnn(CC)c1C)n2C)C(=O)N1C[C@@H](C)O[C@@H](C)C1
InChIKey: QAIGMMZFVFIOOP-VBQJREDUSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 440.55, ALogP 2.38, HBA 9, HBD 1, PSA 102.99, QED 0.63
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(C)c2)nc1N[C@H]1CC[C@@](O)(CC)CC1
InChIKey: IBUKZWFJDDXRON-FVQXVRMNSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9HC35
Assay: Inhibition of recombinant FLAG-tagged EML4-ALK fusion protein (unknown origin) expressed in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 2 days by alamar blue dye based assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 578.81, ALogP 3.9, HBA 9, HBD 4, PSA 122.88, QED 0.35
Compound (SMILES): COc1c(C#N)ccc2[nH]c(-c3cn4c(n3)[C@@H](c3ccccc3C(F)(F)F)OCC4)cc12
InChIKey: ZOVFQRDNBWHWDZ-OAQYLSRUSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of gamma secretase in human SKNBE2 cells expressing human APP695 assessed as increase in Abeta38 levels incubated for 18 hrs by sandwich ELISA
Measurement: IC50 = 347 nM (pChEMBL 6.460000038146973)
Descriptors: MW 438.41, ALogP 5.05, HBA 5, HBD 1, PSA 75.86, QED 0.49
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C1=O
InChIKey: JOORNLXAAOZDNT-DAVSBLIESA-N
Target: Integrin alpha-V/beta-8 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of LAP binding to human integrin alphavbeta8 receptor after 1 hr by solid-phase binding assay
Measurement: IC50 = 59.4 nM (pChEMBL 7.230000019073486)
Descriptors: MW 777.88, ALogP -3.65, HBA 10, HBD 10, PSA 314.42, QED 0.06
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(S(=O)(=O)N2CCC(NC(=O)c3n[nH]cc3NC(=O)c3c(Cl)cc(Cl)cc3Cl)CC2)c1
InChIKey: HZPYSAHDRSBARR-QPJJXVBHSA-N
Target: Cyclin-dependent kinase 14/Cyclin-Y (PROTEIN COMPLEX), Homo sapiens
UniProt: O94921
Assay: Competitive irreversible inhibition of CDK14/cyclin Y (unknown origin) in presence of Km ATP
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 683.02, ALogP 4.26, HBA 7, HBD 4, PSA 156.6, QED 0.23
Compound (SMILES): CCC(Nc1ccc(S(=O)(=O)Nc2nccs2)cc1Cl)c1ccccc1
InChIKey: SDPRTZGVTOHKRX-UHFFFAOYSA-N
Target: SCN1A/SCN1B (PROTEIN COMPLEX), Homo sapiens
UniProt: P35498
Assay: Inhibition of recombinant human full length Nav1.1 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 407.95, ALogP 5.16, HBA 5, HBD 2, PSA 71.09, QED 0.57
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cn(Cc3cccc(N4CCOCC4)c3)c3ccc(F)cc23)[C@H](O)[C@@H]1O
InChIKey: OXOQCSFIVOZOEF-OIYQIAEKSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of NAE (unknown origin) using GST-tagged Ubc12 and Flag-tagged Nedd8 measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 640.69, ALogP 1.43, HBA 12, HBD 4, PSA 182.13, QED 0.18
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1cc(F)ccc1F
InChIKey: KLWKJFRXLGLTIH-VIFPVBQESA-N
Target: SCN1A/SCN1B (PROTEIN COMPLEX), Homo sapiens
UniProt: P35498
Assay: Inhibition of recombinant human full length Nav1.1 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.89, ALogP 5.19, HBA 5, HBD 2, PSA 71.09, QED 0.55
Compound (SMILES): CCOC(=O)c1c(NC(=O)N2CCN(C)CC2)sc2c1CCC2
InChIKey: GPHILACXNMTZEE-UHFFFAOYSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60603
Assay: Agonist activity at TLR1/TLR2 in human THP-1 cells
Measurement: EC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 337.45, ALogP 2.19, HBA 5, HBD 1, PSA 61.88, QED 0.86
Compound (SMILES): COc1ccc(N2C(=O)COc3ccc(-c4cnc5ccccc5c4)cc32)cc1
InChIKey: CELFRCHPJSSCQD-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PI3Kdelta (1 to 1044 residues)/PIK3R1 (1 to 724 residues) expressed in baculovirus expression system using PIP2 as substrate incubated for 2 hrs by ADP-Glo assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.42, ALogP 4.97, HBA 4, HBD 0, PSA 51.66, QED 0.5
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc3c(c2)CCN(C2CC2)CC3)nc1NC1CCOCC1
InChIKey: MPWQARZLUHZHMX-UHFFFAOYSA-N
Target: TEL/AXL (CHIMERIC PROTEIN), Homo sapiens
UniProt: P41212
Assay: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 450.59, ALogP 3.04, HBA 7, HBD 3, PSA 105.4, QED 0.6
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cn(Cc3cccc(Br)c3)c3ccc(F)cc23)[C@H](O)[C@@H]1O
InChIKey: GEVVUAXCPLJANF-KSZWDZKGSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of NAE (unknown origin) using GST-tagged Ubc12 and Flag-tagged Nedd8 measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 634.48, ALogP 2.35, HBA 10, HBD 4, PSA 169.66, QED 0.2
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCCCCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: FANPYQPRSROCKC-PCZBOVPISA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta2/beta3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha6alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 1693.98
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)N[C@H]3CC[C@H](O)CC3)nc3cnc4[nH]ccc4c32)CC1
InChIKey: JFEOTMHLMSEPBP-OPMHRUBESA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK3 in human PBMC assessed as reduction in IL2-induced STAT5 phosphorylation pre-incubated for 30 mins before IL2 stimulation for 30 mins AlphaLISAassay
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 434.54, ALogP 3.52, HBA 6, HBD 3, PSA 119.62, QED 0.57
Compound (SMILES): CC[C@H](Nc1ncnc2c1nc(-c1cnn(CC)c1C)n2C)C(=O)N1C[C@@H](C)O[C@@H](C)C1
InChIKey: QAIGMMZFVFIOOP-VBQJREDUSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 440.55, ALogP 2.38, HBA 9, HBD 1, PSA 102.99, QED 0.63