benzbromarone [Ligand Id: 14007] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL388590 (Benzbromaron, Benzbromarona, Benzbromarone, Benzpromarone, Desuric, L-2214, MJ 10061, MJ-10061, Narcaricin mite, NSC-85433, Uroleap) |
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| DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
|---|---|---|---|---|---|---|---|---|
| phosphodiesterase 4D/3`,5`-cyclic-AMP phosphodiesterase 4D in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL288] [GtoPdb: 1303] [UniProtKB: Q08499] | ||||||||
| ChEMBL | Inhibition of his-tagged recombinant human PDE4D catalytic domain (T86 to S413 residues) expressed in Escherichia coli BL21(DE3) using [3H]-cAMP as substrate incubated for 10 mins by SPA assay | B | 5.68 | pIC50 | 2100 | nM | IC50 | Eur J Med Chem (2023) 262: 115893-115893 [PMID:37918035] |
| 5-HT2B receptor/5-hydroxytryptamine receptor 2B in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1833] [GtoPdb: 7] [UniProtKB: P41595] | ||||||||
| ChEMBL | DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide) | B | 5.94 | pKi | 1148 | nM | Ki | DrugMatrix in vitro pharmacology data |
| ChEMBL | DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide) | B | 5.74 | pIC50 | 1804 | nM | IC50 | DrugMatrix in vitro pharmacology data |
| A3 receptor/Adenosine receptor A3 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL256] [GtoPdb: 21] [UniProtKB: P0DMS8] | ||||||||
| ChEMBL | DRUGMATRIX: Adenosine A3 radioligand binding (ligand: AB-MECA) | B | 5.53 | pKi | 2952 | nM | Ki | DrugMatrix in vitro pharmacology data |
| ChEMBL | DRUGMATRIX: Adenosine A3 radioligand binding (ligand: AB-MECA) | B | 5.28 | pIC50 | 5222 | nM | IC50 | DrugMatrix in vitro pharmacology data |
| Aldo-keto reductase family 1 member C1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5905] [UniProtKB: Q04828] | ||||||||
| ChEMBL | Inhibition of 20-alpha HSD | B | 7.32 | pIC50 | 48 | nM | IC50 | J Med Chem (2009) 52: 3259-3264 [PMID:19397269] |
| Farnesoid X receptor/Bile acid receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2047] [GtoPdb: 603] [UniProtKB: Q96RI1] | ||||||||
| ChEMBL | Agonist activity at FXR (unknown origin) expressed in human HepG2 cells co-transfected with human RXR incubated for 24 hrs by cell-based luciferase transactivation assay | B | 4.61 | pEC50 | 24500 | nM | EC50 | Bioorg Med Chem (2022) 75: 117073-117073 [PMID:36347120] |
| ABCG2/Broad substrate specificity ATP-binding cassette transporter ABCG2 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5393] [GtoPdb: 792] [UniProtKB: Q9UNQ0] | ||||||||
| ChEMBL | Inhibition of ABCG2 (unknown origin) transfected in HEK293 cell membrane vesicle assessed as inhibition of 14C-uric acid uptake incubated for 15 mins in presence of ATP by liquid scintillation counter analysis | B | 6.47 | pIC50 | 340 | nM | IC50 | Eur J Med Chem (2022) 242: 114682-114682 [PMID:36001935] |
| ChEMBL | Inhibition of ABCG2 (unknown origin) expressed in human HEK293-A cells membrane vesicles assessed inhibition of ABCG2-mediated urate transport activity by rapid filtration technique | B | 6.7 | pIC50 | 200 | nM | IC50 | Eur J Med Chem (2022) 237: 114346-114346 [PMID:35483322] |
| CYP2C9/Cytochrome P450 2C9 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3397] [GtoPdb: 1326] [UniProtKB: P11712] | ||||||||
| ChEMBL | DRUGMATRIX: CYP450, 2C9 enzyme inhibition (substrate: 3-Cyano-7-ethoxycoumarin) | B | 7.8 | pIC50 | 16 | nM | IC50 | DrugMatrix in vitro pharmacology data |
| Eyes absent homolog 2 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1293275] [UniProtKB: O00167] | ||||||||
| ChEMBL | Inhibition of human Eya2 catalytic domain by p-nitrophenylphosphate assay | B | 4.99 | pIC50 | 10300 | nM | IC50 | US-20160052904-A1. Use of small molecule inhibitors targeting eya tyrosine phosphatase (2016) |
| ChEMBL | Inhibition of human Eya2 catalytic domain using para-nitrophenol phosphate substrate incubated for 30 mins | B | 4.99 | pIC50 | 10300 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| Eyes absent homolog 3 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4296245] [UniProtKB: Q99504] | ||||||||
| ChEMBL | Inhibition of poly-histidine and GST-tagged full length human Eya3 isoform 2 (127 to 573 residues) using phospho-peptide KKATQASQEpY substrate | B | 4.43 | pIC50 | 37000 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| ChEMBL | Inhibition of human Eya3 isoform 2 (127 to 573 residues) using KKATOASQEpY phospho-peptide substrate | B | 4.43 | pIC50 | 37000 | nM | IC50 | US-20160052904-A1. Use of small molecule inhibitors targeting eya tyrosine phosphatase (2016) |
| ChEMBL | Inhibitory Assay: An inhibitory assay was conducted using the previously described p-nitrophenylphosphate assay (Rayapureddi, J. P. et al. Nature 426, 295-298 (2003)). Briefly, ED was incubated in a reaction mixture containing 20 mM MES pH 6, 2 mM MgCl2, 125 μM inhibitor, 3.4 mM para-nitrophenol phosphate (pNPP) and 0.01 μg/μL enzyme. The amount of 4-nitrophenol (pNP) produced was monitored at 405 nM on a BioTek EL808 plate reader. A similar protocol was used to screen for inhibitor activity using hEYA3 and hEYA2(ED).The compounds were then tested using full-length human recombinant, purified EYA3 and pNPP as a substrate. Compounds were dissolved in DMSO and diluted as needed. IC50 values were determined by adding varying amounts of inhibitor (0-400 μM) to reaction mixtures containing 20 mM MES pH 6, 2 mM MgCl2, 2% DMSO, 3.4 mM pNPP, and 0.01 μg/L enzyme. Reactions were incubated at 30° C. for 30 minutes and quenched with 100 mM EDTA pH 10. IC50 values were then calculated directly from regression curves using PRISM software. All reported values are the mean of two independent experiments.These results were mirrored when an alternate substrate, a 10 amino acid phosphopeptide representing the C-terminus of the known EYA substrate γ-H2AX (Cook, P. J. et al. Nature 458, 591-596, (2009); Krishnan, N. et al. J. Biol. Chem. (2009), the contents of which are incorporated by reference in their entireties). The phospho-peptide KKATQASQEpY (SEQ. ID 5) was obtained from Genscript. Peptide assays were conducted in 20 mM MES pH 6, 2 mM MgCl2, and a range of peptide concentrations from 0 to 300 μM as previously described in the incorporated materials of Rayapureddi, J. P. (2003). IC50 values were then calculated using PRISM software. | B | 4.96 | pIC50 | 11000 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| ChEMBL | Inhibition Assay: The compounds were then tested using full-length human recombinant, purified EYA3 and pNPP as a substrate. Compounds were dissolved in DMSO and diluted as needed. IC50 values were determined by adding varying amounts of inhibitor (0-400 μM) to reaction mixtures containing 20 mM MES pH 6, 2 mM MgCl2, 2% DMSO, 3.4 mM pNPP, and 0.01 μg/μL enzyme. Reactions were incubated at 30° C. for 30 minutes and quenched with 100 mM EDTA pH 10. IC50 values were then calculated directly from regression curves using PRISM software. All reported values are the mean of two independent experiments. | B | 5.08 | pIC50 | 8300 | nM | IC50 | US-9962362-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2018) |
| ChEMBL | Inhibition of poly-histidine and GST-tagged full length human Eya3 isoform 2 (127 to 573 residues) using para-nitrophenol phosphate substrate incubated for 30 mins | B | 5.08 | pIC50 | 8300 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| ChEMBL | Inhibition of human Eya3 isoform 2 (127 to 573 residues) incubated for 30 mins by p-nitrophenylphosphate assay | B | 5.08 | pIC50 | 8300 | nM | IC50 | US-20160052904-A1. Use of small molecule inhibitors targeting eya tyrosine phosphatase (2016) |
| ChEMBL | Inhibitory Assay: An inhibitory assay was conducted using the previously described p-nitrophenylphosphate assay (Rayapureddi, J. P. et al. Nature 426, 295-298 (2003)). Briefly, ED was incubated in a reaction mixture containing 20 mM MES pH 6, 2 mM MgCl2, 125 μM inhibitor, 3.4 mM para-nitrophenol phosphate (pNPP) and 0.01 μg/μL enzyme. The amount of 4-nitrophenol (pNP) produced was monitored at 405 nM on a BioTek EL808 plate reader. A similar protocol was used to screen for inhibitor activity using hEYA3 and hEYA2(ED).The compounds were then tested using full-length human recombinant, purified EYA3 and pNPP as a substrate. Compounds were dissolved in DMSO and diluted as needed. IC50 values were determined by adding varying amounts of inhibitor (0-400 μM) to reaction mixtures containing 20 mM MES pH 6, 2 mM MgCl2, 2% DMSO, 3.4 mM pNPP, and 0.01 μg/L enzyme. Reactions were incubated at 30° C. for 30 minutes and quenched with 100 mM EDTA pH 10. IC50 values were then calculated directly from regression curves using PRISM software. All reported values are the mean of two independent experiments.These results were mirrored when an alternate substrate, a 10 amino acid phosphopeptide representing the C-terminus of the known EYA substrate γ-H2AX (Cook, P. J. et al. Nature 458, 591-596, (2009); Krishnan, N. et al. J. Biol. Chem. (2009), the contents of which are incorporated by reference in their entireties). The phospho-peptide KKATQASQEpY (SEQ. ID 5) was obtained from Genscript. Peptide assays were conducted in 20 mM MES pH 6, 2 mM MgCl2, and a range of peptide concentrations from 0 to 300 μM as previously described in the incorporated materials of Rayapureddi, J. P. (2003). IC50 values were then calculated using PRISM software. | B | 5.08 | pIC50 | 8300 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| Eyes absent homolog 3 in Mouse (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4296244] [UniProtKB: P97480] | ||||||||
| ChEMBL | Inhibition of mouse Eya3 catalytic domain (223 to 510 residues) by p-nitrophenylphosphate assay | B | 4.96 | pIC50 | 11000 | nM | IC50 | US-20160052904-A1. Use of small molecule inhibitors targeting eya tyrosine phosphatase (2016) |
| ChEMBL | Inhibition of mouse Eya3 catalytic domain (223 to 510 residues) using para-nitrophenol phosphate substrate incubated for 30 mins | B | 4.96 | pIC50 | 11000 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| ChEMBL | Inhibition Assay: The compounds were then tested using full-length human recombinant, purified EYA3 and pNPP as a substrate. Compounds were dissolved in DMSO and diluted as needed. IC50 values were determined by adding varying amounts of inhibitor (0-400 μM) to reaction mixtures containing 20 mM MES pH 6, 2 mM MgCl2, 2% DMSO, 3.4 mM pNPP, and 0.01 μg/μL enzyme. Reactions were incubated at 30° C. for 30 minutes and quenched with 100 mM EDTA pH 10. IC50 values were then calculated directly from regression curves using PRISM software. All reported values are the mean of two independent experiments. | B | 4.96 | pIC50 | 11000 | nM | IC50 | US-9962362-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2018) |
| GroEL/GroES in Escherichia coli (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL4106139] [UniProtKB: Q548M1, Q7BGE6] | ||||||||
| ChEMBL | Inhibition of Escherichia coli GroEL expressed in Escherichia coli DH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured rhodanese refolding by measuring rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis | B | 4.31 | pIC50 | 49000 | nM | IC50 | Bioorg Med Chem Lett (2019) 29: 1106-1112 [PMID:30852084] |
| ChEMBL | Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured soluble pig heart MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by malachite green dye based spectrometric analysis | B | 4.74 | pIC50 | 18000 | nM | IC50 | Bioorg Med Chem Lett (2019) 29: 1106-1112 [PMID:30852084] |
| HSP60/HSP10 in Human (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL4106131] [UniProtKB: P10809, P61604] | ||||||||
| ChEMBL | Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis | B | 5.04 | pIC50 | 9100 | nM | IC50 | Bioorg Med Chem Lett (2019) 29: 1106-1112 [PMID:30852084] |
| Inosine-5`-monophosphate dehydrogenase in Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1) (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4523953] [UniProtKB: Q9HXM5] | ||||||||
| ChEMBL | Inhibition of Pseudomonas aeruginosa IMPDH using IMP as substrate in the presence of NAD+ incubated for 70 secs | B | 4.26 | pIC50 | 55000 | nM | IC50 | Eur J Med Chem (2019) 167: 124-132 [PMID:30769241] |
| mitogen-activated protein kinase 1/Mitogen-activated protein kinase 1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4040] [GtoPdb: 1495] [UniProtKB: P28482] | ||||||||
| ChEMBL | DRUGMATRIX: Protein Serine/Threonine Kinase, ERK2 enzyme inhibition (substrate: Myelin Basic Protein) | B | 5.71 | pIC50 | 1946 | nM | IC50 | DrugMatrix in vitro pharmacology data |
| mitogen-activated protein kinase 14/Mitogen-activated protein kinase 14 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL260] [GtoPdb: 1499] [UniProtKB: Q16539] | ||||||||
| ChEMBL | DRUGMATRIX: Protein Serine/Threonine Kinase, p38alpha enzyme inhibition (substrate: Myelin Basic Protein) | B | 5.91 | pIC50 | 1235 | nM | IC50 | DrugMatrix in vitro pharmacology data |
| Monocarboxylate transporter 1 in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2073709] [GtoPdb: 988] [UniProtKB: P53987] | ||||||||
| ChEMBL | TP_TRANSPORTER: inhibition of lactate uptake in Xenopus laevis oocytes | F | 4.66 | pIC50 | 22000 | nM | IC50 | Biochem J (1999) 341: 529-535 [PMID:10417314] |
| Monocarboxylate transporter 2 in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2073718] [GtoPdb: 990] [UniProtKB: Q63344] | ||||||||
| ChEMBL | TP_TRANSPORTER: inhibition of lactate uptake in Xenopus laevis oocytes | F | 5.05 | pIC50 | 9000 | nM | IC50 | Biochem J (1999) 341: 529-535 [PMID:10417314] |
| ABCC1/Multidrug resistance-associated protein 1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3004] [GtoPdb: 779] [UniProtKB: P33527] | ||||||||
| ChEMBL | Inhibition of human MRP1 expressed in Spodoptera frugiperda Sf9 cells assessed as inhibition of NEM-GS-induced vanadate-sensitive ATPase activity measured by generation of inorganic phosphate by spectrophotometry in presence of glutathione | B | 6.72 | pKi | 190 | nM | Ki | Bioorg Med Chem (2011) 19: 3249-3254 [PMID:21530277] |
| ChEMBL | Inhibition of human MRP1 expressed in Spodoptera frugiperda Sf9 cells assessed as inhibition of NEM-GS-induced vanadate-sensitive ATPase activity measured by generation of inorganic phosphate by spectrophotometry in presence of glutathione | B | 5.4 | pIC50 | 4000 | nM | IC50 | Bioorg Med Chem (2011) 19: 3249-3254 [PMID:21530277] |
| ChEMBL | Inhibition of Homo sapiens (human) MRP1 expressed in Sf9 cell membranes assessed as decrease in N-ethyl-maleimide-glutathione-induced inorganic phosphate production by spectrophotometric analysis in presence of glutathione | B | 5.4 | pIC50 | 4000 | nM | IC50 | Med Chem Res (2013) 22: 147-155 |
| Polymerase acidic protein in Influenza A virus (A/Puerto Rico/8/1934(H1N1)) (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1169598] [UniProtKB: P03433] | ||||||||
| ChEMBL | Binding affinity to PA cavity of recombinant Influenza A virus A/PR/8/34(H1N1) PA (239 to 716 residues) measured after 2 mins by SPR analysis | B | 4.32 | pKd | 48200 | nM | Kd | J Med Chem (2016) 59: 7699-7718 [PMID:27046062] |
| Urate anion exchanger 1/Solute carrier family 22 member 12 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL6120] [GtoPdb: 1031] [UniProtKB: Q96S37] | ||||||||
| ChEMBL | Inhibition of human URAT1 expressed in HEK293T cells using 6-carboxylic fluorescein substrate by fluorescence assay | B | 4.57 | pIC50 | 27040 | nM | IC50 | Eur J Med Chem (2024) 271: 116407-116407 [PMID:38663283] |
| ChEMBL | Inhibition of URAT1 in human RPTEC assessed as inhibition of [14C]uric acid uptake preincubated for 15 mins followed by [14C]uric acid addition and incubated under shaking condition for 2 hrs by scintillation counter method | B | 5.17 | pIC50 | 6800 | nM | IC50 | ACS Med Chem Lett (2020) 11: 2017-2023 [PMID:33062187] |
| ChEMBL | Inhibition Assay: URAT1 (Uric Acid Transporter 1) is expressed on the apical membrane in renal tubules. It mediates the re-uptake of uric acid from the urine into the blood. Inhibition of URAT1 leads to increased excretion of uric acid in the urine, and is therefore a potential mode of action for drugs that lower serum uric acid concentrations. Probenecid and Benzbromarone, for example, have been used clinically for treatment of gout and hyperuricemia, and they both act on URAT1 to reduce uric acid reuptake. However, benzbromarone was withdrawn from the market due to liver toxicity via mechanisms independent of URAT1, and probenecid acts on numerous transporter proteins, resulting in interactions with a variety of other drugs.An in vitro URAT1 assay is useful for identifying compounds with potential activity in lowering serum uric acid. A suitable assay involves transfection of cells (e g human embryonic kidney cells "HEK") with a vector encoding human URAT1. | B | 6.12 | pIC50 | 750 | nM | IC50 | US-8889724-B2. Tetrazole compounds for reducing uric acid (2014) |
| ChEMBL | Bioactivity Assay: Human kidney embryonic cells HEK-293T were grown in a petri dish (diameter=10 cm) containing DMEM and 10% of bovine fetal serum culture solution, and incubated in an 5% of carbon dioxide-containing incubator at 37° C. Plasmids carrying human URAT1 were transfected to HEK-293T cells using TransIT-293 (Mirus Bio LLC). After 72 hours, the petri dish containing HEK-293T cells transfected with URAT1 was removed from the incubator and the cells were inoculated on Poly-D-Lysine Coated 96-well Plates at a density of 60,000 cells per well. After the cells on the 96-well plates were grown overnight (at least 12 hours) in an incubator at 37 degrees, these cells were gently rinsed 3 times with warm and no chloride ions-containing HBSS buffer (125 mM sodium gluconate, 4.8 mM potassium gluconate, 1.3 mM calcium gluconate, 1.2 mM monopotassium phosphate, 1.2 mM magnesium sulfate, 5.6 mM glucose, 25 mM HEPES, pH 7.4). 50 microliter of HBSS buffer (not containing chloride ions) containing 0.2 microcurie of 14C-uric acid and compounds of the present application or benzbromarone, and vector was added in each well, then the cell plates were put back to the incubator at 37 degrees. After 5 min, the buffer was removed from cell wells, added with 100 microliter of ice-cold and no chloride ions-containing HBSS buffer to gently rinse cells within wells so as to stop them from absorbing 14C-uric acid, the rinsing was repeated 3 times in the same manner. 150 microliter of cell lysate (100 mM of NaOH) was added in each well. Cell plate was placed on a vibrating plate and vibrated for 10 min at a speed of 600 rpm such that the cells were completely lysed. The cell plate was put in a centrifuge and spun for 5 min at a speed of 1000 rpm, then 45 microliter of supernatant was sucked out from each well and transferred to 96-well plate (Isoplate-96 Microplate from PerkinElmer). | B | 6.26 | pIC50 | 550 | nM | IC50 | US-9856239-B1. Carboxylic acid compound, method for preparation thereof, and use thereof (2018) |
| ChEMBL | Inhibition of URAT1 (unknown origin) | B | 6.28 | pIC50 | 530 | nM | IC50 | Eur J Med Chem (2024) 277: 116753-116753 [PMID:39142150] |
| ChEMBL | Inhibition of human URAT1 stably overexpressing in human HEK293 cells assessed as inhibition of 14C-uric acid uptake preincubated for 30 mins followed by substrate addition and measured after 15 mins using 14C-uric acid as substrate by liquid scintillation counting analysis | B | 6.28 | pIC50 | 530 | nM | IC50 | Eur J Med Chem (2022) 242: 114682-114682 [PMID:36001935] |
| ChEMBL | Inhibition of human URAT1-mediated urate uptake in HEK293 cells | B | 6.52 | pIC50 | 300 | nM | IC50 | Drug Metab Dispos (2007) 35: 981-986 [PMID:17325024] |
| ChEMBL | Inhibition of human URAT1-mediated [8-14C]uric acid uptake expressed in HEK293 cells using [8-14C]uric acid as substrate by liquid scintillation counter analysis | B | 6.52 | pIC50 | 300 | nM | IC50 | J Nat Prod (2023) 86: 24-33 [PMID:36634312] |
| ChEMBL | Inhibition of URAT1 (unknown origin) | B | 6.66 | pIC50 | 220 | nM | IC50 | Eur J Med Chem (2019) 166: 186-196 [PMID:30769179] |
| ChEMBL | Inhibition of human URAT1 expressed in Xenopus laevis oocytes assessed as inhibition of [14C]uric acid uptake measured after 60 mins by liquid scintillation counter method | B | 6.72 | pIC50 | 190 | nM | IC50 | ACS Med Chem Lett (2020) 11: 2017-2023 [PMID:33062187] |
| ChEMBL | Inhibition of human URAT1 expressed in HEK293T cells assessed as reduction in [14C]uric acid uptake measured after 5 mins by liquid scintillation counting method | B | 6.92 | pIC50 | 120 | nM | IC50 | Bioorg Med Chem Lett (2017) 27: 1919-1922 [PMID:28351592] |
| ChEMBL | Inhibition of human URAT1 expressed in Xenopus oocytes by [14C]urate uptake assay | B | 7 | pIC50 | <100 | nM | IC50 | J Med Chem (2020) 63: 3834-3867 [PMID:31774679] |
| ChEMBL | Inhibition of URAT1 (unknown origin) by absorbance based assay | B | 7.32 | pIC50 | 48 | nM | IC50 | J Med Chem (2024) 67: 14668-14691 [PMID:39108024] |
| ChEMBL | Inhibition of human URAT1 expressed in human MDCK cells | B | 7.46 | pIC50 | 35 | nM | IC50 | J Med Chem (2011) 54: 2701-2713 [PMID:21449597] |
| ChEMBL | Inhibition of URAT1 (unknown origin) transfected in dog MDCK cells assessed as inhibition of [14C]uric acid uptake by liquid scintillation counting method | B | 7.46 | pIC50 | 34.5 | nM | IC50 | ACS Med Chem Lett (2020) 11: 2017-2023 [PMID:33062187] |
| ChEMBL | Inhibition of human URAT1 expressed in xenopus oocyte assessed as inhibition of [14C]-labelled urate uptake after 60 mins by liquid scintillation counting | B | 7.59 | pIC50 | 26 | nM | IC50 | J Med Chem (2011) 54: 2701-2713 [PMID:21449597] |
| ChEMBL | Inhibition of URAT1 (unknown origin) | B | 7.66 | pIC50 | 22 | nM | IC50 | Medchemcomm (2016) 7: 1587-1595 |
| Organic anion transporter 1/Solute carrier family 22 member 6 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1641347] [GtoPdb: 1025] [UniProtKB: Q4U2R8] | ||||||||
| ChEMBL | TP_TRANSPORTER: inhibition of Urate uptake (Urate: 300 uM) in OAT1-expressing S2 cells | F | 5.34 | pIC50 | 4600 | nM | IC50 | Kidney Int (2003) 63: 143-155 [PMID:12472777] |
| ChEMBL | Inhibition of OAT1 (unknown origin) transfected in HEK293 cells assessed as inhibition of 6-CFL uptake preincubated for 30 mins followed by 6-CFL addition and measured for 15 mins by fluorescence based microplate reader analysis | B | 5.67 | pIC50 | 2120 | nM | IC50 | Eur J Med Chem (2022) 242: 114682-114682 [PMID:36001935] |
| Solute carrier family 2, facilitated glucose transporter member 9 in Mouse (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5465311] [UniProtKB: Q3T9X0] | ||||||||
| ChEMBL | Inhibition of mouse GLUT9 transfected in human HEK293 cells assessed as inhibition of uric acid induced current by cell patch-clamp assay | B | 4.7 | pIC50 | >20000 | nM | IC50 | Eur J Med Chem (2022) 242: 114682-114682 [PMID:36001935] |
| transthyretin/Transthyretin in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3194] [GtoPdb: 2851] [UniProtKB: P02766] | ||||||||
| ChEMBL | Binding affinity to thyroxin binding site of TTR V30M mutant (unknown origin) expressed in Escherichia coli assessed as quenching of intrinsic tryptophan fluorescence by measuring apparent dissociation constant incubated for 60 mins by fluorescence based analysis | B | 6.7 | pKd | 200 | nM | Kd | Bioorg Med Chem (2023) 90: 117370-117370 [PMID:37311373] |
| ChEMBL | Inhibition of acid mediated TTR V30M mutant aggregation (unknown origin) expressed in Escherichia coli preincubated for 30 mins followed by acetic buffer addition at pH 4.7 and measured after 7 days by thioflavin T based fluorescence analysis | B | 5.24 | pIC50 | 5700 | nM | IC50 | Bioorg Med Chem (2023) 90: 117370-117370 [PMID:37311373] |
| ChEMBL | Inhibition of acid-induced TTR V30M mutant (unknown origin) aggregation preincubated for 30 mins followed by acetate buffer at pH 4.7 addition and measured after 7 days by thioflavin T based fluorescence analysis | B | 5.3 | pIC50 | ~5000 | nM | IC50 | J Med Chem (2024) 67: 6987-7005 [PMID:38670538] |
| protein tyrosine phosphatase non-receptor type 1/Tyrosine-protein phosphatase non-receptor type 1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL335] [GtoPdb: 2976] [UniProtKB: P18031] | ||||||||
| ChEMBL | Inhibition of PTP1B (unknown origin) by p-nitrophenylphosphate assay | B | 4.27 | pIC50 | 53800 | nM | IC50 | US-20160052904-A1. Use of small molecule inhibitors targeting eya tyrosine phosphatase (2016) |
| ChEMBL | Inhibition of PTP1B (unknown origin) using para-nitrophenol phosphate substrate incubated for 30 mins | B | 4.27 | pIC50 | 53800 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| ChEMBL | Inhibitory Assay: An inhibitory assay was conducted using the previously described p-nitrophenylphosphate assay (Rayapureddi, J. P. et al. Nature 426, 295-298 (2003)). Briefly, ED was incubated in a reaction mixture containing 20 mM MES pH 6, 2 mM MgCl2, 125 μM inhibitor, 3.4 mM para-nitrophenol phosphate (pNPP) and 0.01 μg/μL enzyme. The amount of 4-nitrophenol (pNP) produced was monitored at 405 nM on a BioTek EL808 plate reader. A similar protocol was used to screen for inhibitor activity using hEYA3 and hEYA2(ED).The compounds were then tested using full-length human recombinant, purified EYA3 and pNPP as a substrate. Compounds were dissolved in DMSO and diluted as needed. IC50 values were determined by adding varying amounts of inhibitor (0-400 μM) to reaction mixtures containing 20 mM MES pH 6, 2 mM MgCl2, 2% DMSO, 3.4 mM pNPP, and 0.01 μg/L enzyme. Reactions were incubated at 30° C. for 30 minutes and quenched with 100 mM EDTA pH 10. IC50 values were then calculated directly from regression curves using PRISM software. All reported values are the mean of two independent experiments.These results were mirrored when an alternate substrate, a 10 amino acid phosphopeptide representing the C-terminus of the known EYA substrate γ-H2AX (Cook, P. J. et al. Nature 458, 591-596, (2009); Krishnan, N. et al. J. Biol. Chem. (2009), the contents of which are incorporated by reference in their entireties). The phospho-peptide KKATQASQEpY (SEQ. ID 5) was obtained from Genscript. Peptide assays were conducted in 20 mM MES pH 6, 2 mM MgCl2, and a range of peptide concentrations from 0 to 300 μM as previously described in the incorporated materials of Rayapureddi, J. P. (2003). IC50 values were then calculated using PRISM software. | B | 4.27 | pIC50 | 53800 | nM | IC50 | US-9725430-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2017) |
| ChEMBL | Inhibition Assay: The compounds were then tested using full-length human recombinant, purified EYA3 and pNPP as a substrate. Compounds were dissolved in DMSO and diluted as needed. IC50 values were determined by adding varying amounts of inhibitor (0-400 μM) to reaction mixtures containing 20 mM MES pH 6, 2 mM MgCl2, 2% DMSO, 3.4 mM pNPP, and 0.01 μg/μL enzyme. Reactions were incubated at 30° C. for 30 minutes and quenched with 100 mM EDTA pH 10. IC50 values were then calculated directly from regression curves using PRISM software. All reported values are the mean of two independent experiments. | B | 4.27 | pIC50 | 53800 | nM | IC50 | US-9962362-B2. Use of small molecule inhibitors targeting EYA tyrosine phosphatase (2018) |
| Piezo1 in Human [GtoPdb: 2945] [UniProtKB: Q92508] | ||||||||
| GtoPdb | - | - | 5.4 | pIC50 | - | - | - | Blood (2024) 143: 357-369 [PMID:38033286] |
ChEMBL data shown on this page come from version 36:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]
