Details of the Drug

General Information of Drug (ID: DMI7FVQ)

• Drug Name: Metyrapone
• Synonyms: MYT; Mepyrapone; Metapirone; Metapyron; Methapyrapone; Methbipyranone; Methopirapone; Methopyrapone; Methopyrinine; Methopyrone; Metirapona; Metopiron; Metopirone; Metopyrone; Metroprione; Metyrapon; Metyraponum; Alliance Brand of Metyrapone; Metyrapone Alliance Brand; Metyrapone Novartis Brand; Novartis Brand of Metyrapone; Su 4885; METOPIRONE (TN); Metirapona [INN-Spanish]; Metopirone (TN); Metyraponum [INN-Latin]; Su-4885; Metyrapone (JP15/USP/INN); Metyrapone [USAN:INN:BAN:JAN]; 1,2-Di-3-pyridyl-2-methyl-1-propanone; 2-Methyl-1,2-bis(3-pyridyl)-1-propanone; 2-Methyl-1,2-di-3-pyridinyl-1-propanone; 2-Methyl-1,2-di-3-pyridyl-1-propanone; 2-methyl-1,2-dipyridin-3-yl-propan-1-one; 2-methyl-1,2-dipyridin-3-ylpropan-1-one

Indication

Disease Entry	ICD 11	Status	REF
Cushing disease	5A70	Approved	[1]

• Therapeutic Class: Antimetabolites
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 226.27
  Logarithm of the Partition Coefficient (xlogp); 2
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Absorption: The drug is rapidly and well-absorbed orally []
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1 h []
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.9 +/- 0.7 hours [3]
  Metabolism: The drug is metabolized via the hepatic []
• Chemical Identifiers:
  Formula: C14H14N2O
  IUPAC Name: 2-methyl-1,2-dipyridin-3-ylpropan-1-one
  Canonical SMILES: CC(C)(C1=CN=CC=C1)C(=O)C2=CN=CC=C2
  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
  InChIKey: FJLBFSROUSIWMA-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4174
  ChEBI ID: CHEBI:44241
  CAS Number: 54-36-4
  DrugBank ID: DB01011
  TTD ID: D0Q9JT
  ACDINA ID: D00426

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Steroid 11-beta-hydroxylase (CYP11B1)	TTIQUX7	C11B1_HUMAN	Inhibitor	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Gene/Protein Processing	[5]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[5]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Gene/Protein Processing	[6]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)	OT02MSKN	3BHS2_HUMAN	Gene/Protein Processing	[6]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Gene/Protein Processing	[7]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[8]
Dehydrogenase/reductase SDR family member 7 (DHRS7)	OTV729DT	DHRS7_HUMAN	Biotransformations	[9]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[10]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Gene/Protein Processing	[10]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Gene/Protein Processing	[11]

Molecular Expression Atlas of This Drug

• The Studied Disease: Cushing disease
• ICD Disease Classification: 5A70

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Steroid 11-beta-hydroxylase (CYP11B1)	DTT	CYP11B1	4.31E-04	-0.03	-0.13

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Ethyl vanillin	E00178	8467	Flavoring agent
Propylparaben sodium	E00567	23679044	Antimicrobial preservative
Glycerin	E00026	753	Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Metyrapone 250 mg capsule	250 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5224).
• [2] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 2002 Apr;16(2):113-21.
• [5] In the search for specific inhibitors of human 11beta-hydroxysteroid-dehydrogenases (11beta-HSDs): chenodeoxycholic acid selectively inhibits 11beta-HSD-I. Eur J Endocrinol. 2000 Feb;142(2):200-7.
• [6] The H295R system for evaluation of endocrine-disrupting effects. Ecotoxicol Environ Saf. 2006 Nov;65(3):293-305.
• [7] Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab Dispos. 2003 Nov;31(11):1296-9. doi: 10.1124/dmd.31.11.1296.
• [8] A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Xenobiotica. 1999 Mar;29(3):269-79.
• [9] Biochemical properties of human dehydrogenase/reductase (SDR family) member 7. Chem Biol Interact. 2014 Jan 25;207:52-7. doi: 10.1016/j.cbi.2013.11.003. Epub 2013 Nov 16.
• [10] In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest. 2006 Sep;36(9):647-53. doi: 10.1111/j.1365-2362.2006.01700.x.
• [11] Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone. Biol Psychiatry. 2006 Oct 1;60(7):784-7. doi: 10.1016/j.biopsych.2006.01.014. Epub 2006 Mar 29.