liarozole [Ligand Id: 5210] activity data from GtoPdb and ChEMBL

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ChEMBL ligand: CHEMBL389433 (Liarozol, Liarozole)
  • CYP24A1/1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial in Human [ChEMBL: CHEMBL4521] [GtoPdb: 1365] [UniProtKB: Q07973]
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DB Assay description Assay Type Standard value Standard parameter Original value Original units Original parameter Reference
CYP24A1/1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4521] [GtoPdb: 1365] [UniProtKB: Q07973]
ChEMBL Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC method B 8.64 pIC50 2.3 nM IC50 J Med Chem (2014) 57: 7702-7715 [PMID:25148392]
CYP19A1/Aromatase in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1978] [GtoPdb: 1362] [UniProtKB: P11511]
ChEMBL Inhibition of human placental microsome CYP19 B 7.35 pIC50 44.67 nM IC50 J Med Chem (2005) 48: 7282-7289 [PMID:16279787]
ChEMBL Inhibition of human placental microsome CYP19 B 8.3 pIC50 5 nM IC50 Bioorg Med Chem Lett (2010) 20: 3050-3064 [PMID:20413308]
CYP26A1/Cytochrome P450 26A1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5141] [GtoPdb: 1366] [UniProtKB: O43174]
ChEMBL Inhibition of CYP26A1 in human MCF7 cells B 5.15 pIC50 7000 nM IC50 Bioorg Med Chem (2008) 16: 8301-8313 [PMID:18722776]
ChEMBL Potency towards cytochrome P 450 26 enzyme activity B 5.22 pIC50 6000 nM IC50 Bioorg Med Chem Lett (2005) 15: 1669-1673 [PMID:15745819]
ChEMBL Inhibition of CYP26A1 in ATRA-induced human HL60 cell microsomes incubated for 30 mins using ATRA and NADPH by HPLC method B 5.61 pIC50 2450 nM IC50 Bioorg Med Chem (2015) 23: 1356-1365 [PMID:25684424]
GtoPdb - - 5.7 pIC50 - - - Mol Pharmacol (2011) 80: 228-39 [PMID:21521770]
ChEMBL Inhibition of microsomal fraction of human CYP26A1 expressed in Sf9 cells using 9-cis-RA as substrate preincubated for 5 mins followed by NADPH addition measured after 1 min by HPLC analysis in presence of rat P450 reductase B 5.72 pIC50 1900 nM IC50 J Med Chem (2016) 59: 2579-2595 [PMID:26918322]
ChEMBL Inhibition Assay: Eighteen compounds were tested as potential inhibitors of CYP26A1 and CYP26B1. The formation of 9-cis-4-OH-RA metabolite was monitored and the percent activity remaining in the presence of the inhibitor in comparison to the solvent only control was quantified. B 5.72 pIC50 1900 nM IC50 US-9963439-B2. Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase (2018)
ChEMBL Inhibition of CYP26A1 in ATRA-induced human HL60 cell microsomes incubated for 30 mins in dark condition with NADPH and ATRA by HPLC method B 6.05 pIC50 890 nM IC50 Bioorg Med Chem (2015) 23: 6763-6773 [PMID:26365710]
ChEMBL Inhibition of human CYP26A1 assessed using [11,12-3H]ATRA as substrate by scintillation counting B 6.27 pIC50 540 nM IC50 J Med Chem (2011) 54: 6803-6811 [PMID:21838328]
ChEMBL Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting B 6.27 pIC50 540 nM IC50 J Med Chem (2011) 54: 2778-2791 [PMID:21428449]
CYP26B1/Cytochrome P450 26B1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3713687] [GtoPdb: 1367] [UniProtKB: Q9NR63]
ChEMBL Inhibition of microsomal fraction of human CYP26B1 expressed in Sf9 cells using 9-cis-RA as substrate preincubated for 5 mins followed by NADPH addition measured after 5 mins by HPLC analysis in presence of rat P450 reductase B 7.74 pIC50 18 nM IC50 J Med Chem (2016) 59: 2579-2595 [PMID:26918322]
ChEMBL Inhibition Assay: Eighteen compounds were tested as potential inhibitors of CYP26A1 and CYP26B1. The formation of 9-cis-4-OH-RA metabolite was monitored and the percent activity remaining in the presence of the inhibitor in comparison to the solvent only control was quantified. B 7.74 pIC50 18 nM IC50 US-9963439-B2. Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase (2018)
CYP2C8/Cytochrome P450 2C8 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3721] [GtoPdb: 1325] [UniProtKB: P10632]
ChEMBL Inhibition Assay: Compounds were assessed for inhibition (IC50, n=2) of CYP2C8, CYP2C9 and CYP3A4 in pooled human liver microsomes using selective probe substrates at their previously determined Km values (CYP2C8: paclitaxel, 4 μM; CYP2C9: diclofenac, 5 μM; CYP3A4: midazolam, 0.5 μM). Incubations contained 0.1 mg/mL human liver microsomes, 3 mM MgCl2, probe substrate and various concentrations of inhibitor (12-point IC50 curve) in 100 mM potassium phosphate buffer (pH 7.4). Concentrations of organic solvents were kept to <1% (v/v). All incubations were pre-incubated at 37° C. for 5 minutes prior to addition of 1 mM NADPH (final concentration). Incubations were stopped after 5 (CYP3A4) or 15 minutes (CYP2C8 and CYP2C9) with one volume (v/v) of ice-cold acetonitrile containing 0.1 μM tolbutamide as an internal standard. All samples were vortexed and centrifuged prior to LC-MS/MS analysis. B 6.32 pIC50 480 nM IC50 US-9963439-B2. Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase (2018)
CYP2C9/Cytochrome P450 2C9 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3397] [GtoPdb: 1326] [UniProtKB: P11712]
ChEMBL Inhibition Assay: Compounds were assessed for inhibition (IC50, n=2) of CYP2C8, CYP2C9 and CYP3A4 in pooled human liver microsomes using selective probe substrates at their previously determined Km values (CYP2C8: paclitaxel, 4 μM; CYP2C9: diclofenac, 5 μM; CYP3A4: midazolam, 0.5 μM). Incubations contained 0.1 mg/mL human liver microsomes, 3 mM MgCl2, probe substrate and various concentrations of inhibitor (12-point IC50 curve) in 100 mM potassium phosphate buffer (pH 7.4). Concentrations of organic solvents were kept to <1% (v/v). All incubations were pre-incubated at 37° C. for 5 minutes prior to addition of 1 mM NADPH (final concentration). Incubations were stopped after 5 (CYP3A4) or 15 minutes (CYP2C8 and CYP2C9) with one volume (v/v) of ice-cold acetonitrile containing 0.1 μM tolbutamide as an internal standard. All samples were vortexed and centrifuged prior to LC-MS/MS analysis. B 5.79 pIC50 1630 nM IC50 US-9963439-B2. Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase (2018)
CYP3A4/Cytochrome P450 3A4 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL340] [GtoPdb: 1337] [UniProtKB: P08684]
ChEMBL Inhibition Assay: Compounds were assessed for inhibition (IC50, n=2) of CYP2C8, CYP2C9 and CYP3A4 in pooled human liver microsomes using selective probe substrates at their previously determined Km values (CYP2C8: paclitaxel, 4 μM; CYP2C9: diclofenac, 5 μM; CYP3A4: midazolam, 0.5 μM). Incubations contained 0.1 mg/mL human liver microsomes, 3 mM MgCl2, probe substrate and various concentrations of inhibitor (12-point IC50 curve) in 100 mM potassium phosphate buffer (pH 7.4). Concentrations of organic solvents were kept to <1% (v/v). All incubations were pre-incubated at 37° C. for 5 minutes prior to addition of 1 mM NADPH (final concentration). Incubations were stopped after 5 (CYP3A4) or 15 minutes (CYP2C8 and CYP2C9) with one volume (v/v) of ice-cold acetonitrile containing 0.1 μM tolbutamide as an internal standard. All samples were vortexed and centrifuged prior to LC-MS/MS analysis. B 5 pIC50 10000 nM IC50 US-9963439-B2. Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase (2018)
ChEMBL null: A commercially available P450-GLO Assay kit (Promega Corporation, Madison Wis.) is used to screen various compounds for CYP3A4A inhibition activity. CYP3A4A is thought to be one of the primary CYP isoforms responsible for retinoic acid metabolism in the skin. Three benchmark agents, liarozole, climbazole, and ketoconazole, were assessed for CYP3A4 inhibition to confirm that the inhibition activity (the IC50 for CYP3A4 inhibition) measured by the assay corresponds to the activity reported by the published literature. The results show that the substituted azole compounds having the specific structure set forth herein are CYP inhibitors, and thus function as RAMBAs. B 7 pIC50 <100 nM IC50 US-9138393-B2. Cosmetic compositions containing substituted azole and methods for improving the appearance of aging skin (2015)
ChEMBL In vitro CYP3A4 Inhibition Assay: Cytochrome P450 is a large and diverse group of enzymes that catalyze the oxidation of organic substances. Some members of the CYP family contribute to the elimination of ATRA by catalyzing its 4-hydroxylation in the mammalian liver and skin, including that of humans as well as swine. Applicant evaluated the potential RAMBA activity of several azoles using pig liver microsomes, a rich source of CYP activity, comprising many different CYP 450 isoforms. Therefore, this approach, while a reasonable way to assess CYP inhibitors with broad activities may or may not be the best way to discover RAMBAs with selectivity for the skin, which has a much more narrow complement of CYP expression. As understanding in this area has progressed, a more specific CYP inhibition assay can be used to provide better predictivity of activity in human skin. Nevertheless, this assay may still be used as a general predictor of overall CYP activity. B 7 pIC50 <100 nM IC50 US-9144538-B2. Cosmetic compositions containing substituted azole and methods for alleviating the signs of photoaged skin (2015)

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]