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

General Information of Drug (ID: DM70DTN)

• Drug Name: Flibanserin Drug Info
• Synonyms: Flibanserin [USAN]; Bimt 17; Bimt-17; 1,3-Dihydro-1-(2-(4-(3-(trifluoromethyl)phenyl)-1-piperazinyl)ethyl)-2H-benzimidazol-2-one; 1-(2-(4-(3-Trifluoromethylphenyl)piperazin-1-yl)ethyl)benzimidazol(1H)-2-one; 1-(2-(4-(alpha,alpha,alpha-Trifluoro-m-tolyl)-1-piperazinyl)ethyl)-2-benzimidazolinone; 1-(2-(4-alpha,alpha,alpha-Trifluoro-m-tolyl)-1-piperazinyl)ethyl)-2-benzimidazolinone; 3-[2-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]ethyl]-1H-benzimidazol-2-one

Indication

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[1]
Hypoactive sexual desire disorder		Approved	[1]
Mood disorder	6A60-6E23	Approved	[2]
Psychosexual disorder		Approved	[1]
Female sexual arousal dysfunction	HA01.1	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 6918248
  ChEBI ID: CHEBI:90865
  CAS Number: CAS 167933-07-5
  TTD Drug ID: DM70DTN
  INTEDE Drug ID: DR0701
  ACDINA Drug ID: D00279

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 2A receptor (HTR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[6]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[7]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[8]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[9]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[10]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[11]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[12]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[13]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[14]
TRYPTAMINE	DMAFPHB	N. A.	N. A.	Phase 3	[15]

Drug(s) Targeting 5-HT 1A receptor (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[16]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[17]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[18]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[19]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[20]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[21]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[22]
Treximet	DMU54QB	Migraine	8A80	Approved	[23]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[24]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[25]

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	[26]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[27]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[28]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[29]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[30]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[31]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[32]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[33]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[27]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[34]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[35]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[36]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[37]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[38]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[39]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[40]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[41]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[42]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[43]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[44]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Modulator	[3]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[5]

References

• [1] Flibanserin FDA Label
• [2] 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: 8182).
• [3] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [4] Flibanserin: first global approval. Drugs. 2015 Oct;75(15):1815-22.
• [5] Flibanserin therapy and CYP2C19 genotype.
• [6] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [7] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [8] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [9] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [10] Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [12] Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
• [13] Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
• [14] Clinical pipeline report, company report or official report of Lundbeck.
• [15] Central serotonin receptors as targets for drug research. J Med Chem. 1987 Jan;30(1):1-12.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [17] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [18] Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
• [19] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [20] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [21] Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
• [22] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [23] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [24] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [25] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [26] 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.
• [27] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [28] 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.
• [29] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [30] 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.
• [31] 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.
• [32] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [33] 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.
• [34] 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.
• [35] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [36] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [37] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [38] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [39] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [40] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [41] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [42] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [43] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [44] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.