Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMZSWQC)

• Drug Name: Flunisolide Drug Info
• Synonyms: Aerobid; Aerospan; Bronalide; Flunisolida; Flunisolidum; Lunis; Nasalide; Nasarel; Nisolid; Rhinalar; Rhinolar; Soluzione; Synaclyn; Syntaris; Aerobid M; Aerospan HFA; Flunisolide HFA; Flunisolide [INN]; Flunisolide [anhydrous]; Flunisolide anhydrous; F0437; RS 3999; AeroBid (TN); Flunisolida [INN-Spanish]; Flunisolide (anhydrous); Flunisolidum [INN-Latin]; Nasalide (TN); Nasarel (TN); RS-3999; AeroBid, Nasalide, Nasarel,Flunisolide; Pregna-1,4-diene-3,20-dione, 6-alpha-fluoro-11-beta,16-alpha,17,21-tetrahydroxy-, cyclic 16,17-acetal with acetone; Pregna-1,4-diene-3,20-dione, 6-alpha-fluoro-11-beta,16-alpha,17,21-tetrahydroxy-,cyclic 16,17-acetal with acetone; 6 alpha-fluoro-11 beta,16 alpha,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16, 17-acetal with acetone; 6 alpha-fluorodihydroxy-16 alpha,17 alpha-isopropylidenedioxy-1,4-pregnadiene-3,20-dione; 6-Fluoro-11,21-dihydroxy-16,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione; 6alpha-Fluoro-11beta,16alpha,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16, 17-acetal with acetone; 6alpha-fluoro-11beta,21-dihydroxy-16alpha,17alpha-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione

Indication

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[1]
Asthma	CA23	Investigative	[2]

• Therapeutic Class: Antiasthmatic Agents
• Cross-matching ID:
  PubChem CID: 82153
  ChEBI ID: CHEMBL1512
  CAS Number: CAS 3385-03-3
  TTD Drug ID: DMZSWQC
  INTEDE Drug ID: DR0710
  ACDINA Drug ID: D01088

Molecule-Related Drug Atlas

Drug(s) Targeting Glucocorticoid receptor (NR3C1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[6]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[7]
Prednisolone	DMQ8FR2	Acute adrenal insufficiency		Approved	[8]
Fluticasone	DMGCSVF	Allergic rhinitis	CA08.0	Approved	[9]
Betamethasone Valerate	DMMIAXO	Dermatological disease	DA24.Y	Approved	[7]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[7]
Deflazacort	DMV0RNS	Duchenne dystrophy	8C70	Approved	[7]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[10]
Budesonide	DMJIBAW	Allergic rhinitis	CA08.0	Approved	[11]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[12]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

Drug(s) Affected By Nuclear receptor subfamily 1 group I member 2 (NR1I2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]
Vidarabine	DM0N85H	Hepatosplenic T-cell lymphoma		Approved	[22]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[23]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[24]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[5]
Etidronic acid	DM1XHYJ	Bone Paget disease		Approved	[22]
Tiaprofenic acid	DM23D7J	Osteoarthritis	FA00-FA05	Approved	[22]
Bromperidol	DM24XYQ	Schizophrenia	6A20	Approved	[22]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[5]

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: 7076).
• [2] Flunisolide FDA Label
• [3] The glucocorticoid receptor heterocomplex gene STIP1 is associated with improved lung function in asthmatic subjects treated with inhaled corticost... J Allergy Clin Immunol. 2009 Jun;123(6):1376-83.e7.
• [4] Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes. Drug Metab Dispos. 2013 Feb;41(2):379-89.
• [5] Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
• [6] Interaction between the glucocorticoid and erythropoietin receptors in human erythroid cells. Exp Hematol. 2009 May;37(5):559-72.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice. Laryngoscope. 2000 Nov;110(11):1902-6.
• [9] Fluticasone furoate nasal spray in allergic rhinitis. Drugs Today (Barc). 2008 Apr;44(4):251-60.
• [10] Cytochromes P450 (CYP) in the Poeciliopsis lucida hepatocellular carcinoma cell line (PLHC-1): dose- and time-dependent glucocorticoid potentiation of CYP1A induction without induction of CYP3A. ArchBiochem Biophys. 1996 May 1;329(1):113-22.
• [11] PXR-mediated induction of human CYP3A4 and mouse Cyp3a11 by the glucocorticoid budesonide. Eur J Pharm Sci. 2009 Mar 2;36(4-5):565-71.
• [12] The glucocorticoid agonist activities of mifepristone (RU486) and progesterone are dependent on glucocorticoid receptor levels but not on EC50 values. Steroids. 2007 Jun;72(6-7):600-8.
• [13] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [18] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [21] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [22] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [23] Induction of PXR-mediated metabolism by beta-carotene. Biochim Biophys Acta. 2005 May 30;1740(2):162-9. doi: 10.1016/j.bbadis.2004.11.013. Epub 2004 Dec 8.
• [24] Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol. 2005 Dec 1;209(2):123-33. doi: 10.1016/j.taap.2005.03.015.
• [25] Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
• [26] Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.