METYRAPONE

/static/temp/default.svg Search structure
Trade Names
Synonyms
Status
Molecule Category Free-form
ATC V04CD01
UNII ZS9KD92H6V
EPA CompTox DTXSID1023314

Structure

InChI Key FJLBFSROUSIWMA-UHFFFAOYSA-N
Smiles CC(C)(C(=O)c1cccnc1)c1cccnc1
InChI
InChI=1S/C14H14N2O/c1-14(2,12-6-4-8-16-10-12)13(17)11-5-3-7-15-9-11/h3-10H,1-2H3

Physicochemical Descriptors

Property Name Value
Molecular Formula C14H14N2O
Molecular Weight 226.28
AlogP 2.64
Hydrogen Bond Acceptor 3.0
Hydrogen Bond Donor 0.0
Number of Rotational Bond 3.0
Polar Surface Area 42.85
Molecular species NEUTRAL
Aromatic Rings 2.0
Heavy Atoms 17.0
Assay Description Organism Bioactivity Reference
Inhibition of CYP450-mediated tangeretin demethylation in Aspergillus niger ATCC 9142 assessed as relative activity at 0.5 mM Aspergillus niger 40.0 %
Displacement of [131I]IMTO from CYP450c 11 in Wistar rat adrenal membrane Rattus norvegicus 1.16 nM
Inhibition of human aldosterone synthase expressed in chinese hamster V79 cells at 500 nM using 11-deoxycorticosterone as substrate Homo sapiens 79.0 %
Inhibition of human steroid-11beta-hydroxylase expressed in chinese hamster V79 cells at 500 nM using 11-deoxycorticosterone as substrate Homo sapiens 94.0 %
Inhibition of human aldosterone synthase expressed in chinese hamster V79 cells using 11-deoxycorticosterone as substrate Homo sapiens 72.0 nM
Inhibition of human steroid-11beta-hydroxylase expressed in chinese hamster V79 cells using 11-deoxycorticosterone as substrate Homo sapiens 14.6 nM
Inhibition of human CYP17 expressed in Escherichia coli at 2000 nM using progesterone as substrate Homo sapiens 0.0 %
Inhibition of human placental CYP19 at 500 nM using androstenedione as substrate Homo sapiens 0.0 %
Inhibition of human CYP11B1 expressed in hamster V79MZ cells using 11-deoxycorticosterone substrate Homo sapiens 15.0 nM
Inhibition of human CYP11B2 expressed in hamster V79MZ cells using 11-deoxycorticosterone substrate Homo sapiens 72.0 nM
DRUGMATRIX: CYP450, 3A4 enzyme inhibition (substrate: 7-Benzyloxy-4-(trifluoromethyl)-coumarin) None 800.0 nM
Inhibition of human CYP11B1 expressed in hamster V79 MZ cells using [3H] 11 deoxycorticosterone as substrate by HPLC radioflow detector Homo sapiens 15.0 nM
Inhibition of human CYP11B2 expressed in hamster V79 MZ cells using [3H] 11 deoxycorticosterone as substrate by HPLC radioflow detector Homo sapiens 72.0 nM
Inhibition of microsomal CYP19 in human placenta using [1beta-3H]-androstenedione as substrate at 2 uM by 3H2O method relative to control Homo sapiens 0.0 %
Inhibition of human CYP17 expressed in Escherichia coli co-expressing rat NADPH-P450 reductase using progesterone as substrate at 2 uM relative to control Homo sapiens 3.0 %
Inhibition of human CYP11B2 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxycorticosterone as substrate Homo sapiens 42.0 nM
Inhibition of human CYP11B1 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxycorticosterone as substrate Homo sapiens 15.0 nM
Inhibition of CYP11B1 (unknown origin) expressed in Chinese hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate at 500 nM preincubated for 60 mins followed by substrate addition measured after 25 mins by HPLC analysis relative to control Homo sapiens 98.0 %
Inhibition of CYP11B1 (unknown origin) expressed in Chinese hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate preincubated for 60 mins followed by substrate addition measured after 25 mins by HPLC analysis Homo sapiens 14.6 nM
Inhibition of CYP11B2 (unknown origin) expressed in Chinese hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate at 500 nM preincubated for 60 mins followed by substrate addition measured after 50 mins by HPLC analysis relative to control Homo sapiens 95.0 %
Inhibition of CYP11B2 (unknown origin) expressed in Chinese hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate preincubated for 60 mins followed by substrate addition measured after 50 mins by HPLC analysis Homo sapiens 71.8 nM
Inhibition of human CYP17 expressed in Escherichia coli using progesterone as substrate at 2 uM preincubated for 5 mins followed by enzyme addition measured after 30 mins by HPLC analysis relative to control Homo sapiens 0.0 %
Inhibition of CYP19 isolated from microsomal fraction of human term placental tissue using [1beta-3H] androstenedione as substrate at 2 uM preincubated for 5 mins followed by enzyme addition measured after 20 mins by beta scintillation counting analysis relative to control Homo sapiens 0.0 %
Inhibition of bovine adrenal gland 11beta-hydroxylase assessed as inhibition of [14C]-deoxycorticosterone hydroxylation at 2 uM Bos taurus 68.0 %
Inhibition of bovine adrenal gland 11beta-hydroxylase assessed as inhibition of [14C]-deoxycorticosterone hydroxylation Bos taurus 580.0 nM
Inhibition of bovine adrenal gland 11beta-hydroxylase assessed as amount of corticosterone production using 22 nmol [14C]-deoxycorticosterone measured per 5 mins at 2 nmol Bos taurus 68.0 %
Inhibition of bovine adrenal gland 11beta-hydroxylase assessed as amount of corticosterone production using 11 nmol [14C]-deoxycorticosterone measured per 5 mins at 2 nmol Bos taurus 70.0 %
Inhibition of human CYP11B1 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxycorticosterone as substrate Homo sapiens 15.0 nM
Inhibition of human CYP17 expressed in Escherichia coli using progesterone as substrate at 2 uM Homo sapiens 3.0 %
Inhibition of human placental CYP19 using [1beta-3H]androstenedione as substrate at 2 uM by 3H2O-method Homo sapiens 0.0 %
Inhibition of human CYP11B2 expressed in hamster V79MZh cells using [1,2-3H]-11-deoxycorticosterone as substrate Homo sapiens 72.0 nM
Inhibition of human placental microsomal CYP19 using [1beta-3H]androstenedione substrate pre-incubated for 5 mins by scintillation counting method Homo sapiens 0.0 nM
Inhibition of human CYP17 expressed in Escherichia coli using [3H]-progesterone substrate pre-incubated for 5 mins at 2.5 uM in presence of rat P450 reductase by HPLC method Homo sapiens 3.0 %
Inhibition of human CYP11B1 expressed in hamster V79MZh11B1 cells using [1,2-3H]-11-deoxycorticosterone substrate incubated for 25 mins by HPLC method Homo sapiens 15.0 nM
Inhibition of human CYP11B2 expressed in hamster V79MZh11B2 cells using [1,2-3H]-11-deoxycorticosterone substrate incubated for 25 mins by HPLC method Homo sapiens 72.0 nM
Inhibition of human aldosterone synthase expressed in V79 MZ cells pretreated with compound for 1 hr followed by addition of 500 nM 11-deoxycorticosterone for 1hr by HPLC analysis Homo sapiens 208.0 nM
Inhibition of human CYP11B1 expressed in V79 MZ cells pretreated with compound for 1 hr followed by addition of 500 nM 11-deoxycorticosterone for 3 hrs by HPLC analysis Homo sapiens 46.0 nM
Inhibition of human CYP11B1 expressed in hamster fibroblast using 100 nM [3H]-11-deoxycorticosterone as substrate after 25 mins by HPLC analysis Homo sapiens 15.0 nM
Inhibition of human CYP11B2 expressed in hamster fibroblast using 100 nM [3H]-11-deoxycorticosterone as substrate after 45 mins by HPLC analysis Homo sapiens 72.0 nM
Cellular Inhibition Assay: V79MZ cells expressing human CYP11B1 and human CYP11B2 genes, respectively, were grown on 24-well cell culture plates (8×10^5 cells per well) with 1.9 cm^2 culture area per well in 1 ml DMEM culture medium until confluence. Before testing, the DMEM culture medium was removed and 450 μl of fresh DMEM, containing the inhibitor in at least three different concentrations for determining the IC50 value, was added to each well. Every value was determined at least three times. After a pre-incubation step of 60 min at 37° C., the reaction was started by the addition of 50 μl of DMEM containing the substrate 11-deoxycorticosterone (containing 0.15 μCi of [1,2-3H] 11-deoxycorticosterone, dissolved in ethanol, final concentration 100 nM). The V79MZh11B1 cells were incubated for 25 min, the V79MZh11B2 cells were incubated for 50 min. Controls were treated in the same way without inhibitors. The maximum DMSO concentration in each well was 1%. Enzyme reactions were stopped by extracting the supernatant with 500 μl ethyl acetate. Samples were centrifuged (10000×g, 2 min), and the solvent was pipetted into fresh cups. The solvent was evaporated and the steroids were redissolved in 40 μl of methanol and analyzed by HPLC using radioflow detection (Ehmer et al. J. Steroid Biochem. Mol. Biol. 2002, 81, 173-179 and Denner et al. Endocr. Res. 1995, 21, 443-448). Homo sapiens 15.0 nM
Cellular Inhibition Assay: V79MZ cells expressing human CYP11B1 and human CYP11B2 genes, respectively, were grown on 24-well cell culture plates (8×10^5 cells per well) with 1.9 cm^2 culture area per well in 1 ml DMEM culture medium until confluence. Before testing, the DMEM culture medium was removed and 450 μl of fresh DMEM, containing the inhibitor in at least three different concentrations for determining the IC50 value, was added to each well. Every value was determined at least three times. After a pre-incubation step of 60 min at 37° C., the reaction was started by the addition of 50 μl of DMEM containing the substrate 11-deoxycorticosterone (containing 0.15 μCi of [1,2-3H] 11-deoxycorticosterone, dissolved in ethanol, final concentration 100 nM). The V79MZh11B1 cells were incubated for 25 min, the V79MZh11B2 cells were incubated for 50 min. Controls were treated in the same way without inhibitors. The maximum DMSO concentration in each well was 1%. Enzyme reactions were stopped by extracting the supernatant with 500 μl ethyl acetate. Samples were centrifuged (10000×g, 2 min), and the solvent was pipetted into fresh cups. The solvent was evaporated and the steroids were redissolved in 40 μl of methanol and analyzed by HPLC using radioflow detection (Ehmer et al. J. Steroid Biochem. Mol. Biol. 2002, 81, 173-179 and Denner et al. Endocr. Res. 1995, 21, 443-448). Homo sapiens 72.0 nM
Inhibition of human CYP11B1 expressed in hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate after 6 hrs by HPLC analysis Homo sapiens 15.0 nM
Inhibition of human CYP11B2 expressed in hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate after 6 hrs by HPLC analysis Homo sapiens 72.0 nM
Inhibition of human CYP11B1 expressed in hamster V79MZ cells using [1,2-3H]-11-deoxycorticosterone as substrate after 6 hrs by HPTLC analysis Homo sapiens 15.0 nM
Inhibition of human placental microsomal CYP19A1 at 2 uM using [1beta-3H]androstenedione after 21 mins by liquid scintillation spectrometry Homo sapiens 0.0 %
Inhibition of human CYP17A1 expressed in Escherichia coli XL1 at 2 uM using [3H]-progesterone as substrate preincubated with substrate for 5 mins measured after 45 mins by HPLC analysis Homo sapiens 3.0 %
Inhibition of human 11beta-HSD1 expressed in HEK293 cell lysates at 200 uM using [1,2-3H]-cortisone as substrate preincubated for 10 mins followed by substrate addition in presence of NADPH by scintillation counting relative to control Homo sapiens 70.0 %
Inhibition of human 11beta-HSD1 expressed in HEK293 cell lysates at 50 uM using [1,2-3H]-cortisone as substrate preincubated for 10 mins followed by substrate addition in presence of NADPH by scintillation counting relative to control Homo sapiens 54.0 %
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600) Staphylococcus aureus subsp. aureus 4.18 %
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600) Escherichia coli 6.34 %
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600) Klebsiella pneumoniae 19.17 %
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600) Pseudomonas aeruginosa 18.6 %
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600 Acinetobacter baumannii 20.43 %
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630 Candida albicans 2.49 %
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570) Cryptococcus neoformans -9.27 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -2.14 %
Inhibition of cytochrome P450 in Sprague-Dawley rat liver microsomes assessed as inhibition of NADPH-dependent retinoic acid oxidation at 100 uM incubated for 5 mins followed by retinoic acid addition and further incubated for 60 mins by HPLC analysis relative to control Rattus norvegicus 47.0 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 18.25 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 10.65 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.19 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.03 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.19 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.03 %

Cross References

Resources Reference
ChEBI 44241
ChEMBL CHEMBL934
DrugBank DB01011
DrugCentral 1791
FDA SRS ZS9KD92H6V
Human Metabolome Database HMDB0015146
Guide to Pharmacology 5224
KEGG C07205
PDB MYT
PharmGKB PA450486
PubChem 4174
SureChEMBL SCHEMBL637432
ZINC ZINC000000001728
CONTENTS