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

General Information of Drug (ID: DMEROU4)

• Drug Name: Tolafentrine Drug Info
• Synonyms: BY-4070

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 65990
  CAS Number: CAS 139308-65-9
  TTD Drug ID: DMEROU4
  VARIDT Drug ID: DR01363

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 3 (PDE3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[4]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[4]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[5]
Enoximone	DMQVZJD	Congestive heart failure	BD10	Approved	[6]
Olprinone	DMWBQKU	Heart failure	BD10-BD13	Approved	[7]
Inamrinone Lactate	DMRMFP4	Cardiac disease	BA00-BE2Z	Approved	[8]
Milrinone	DM8TUPF	Congestive heart failure	BD10	Approved	[4]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[9]
Tipelukast	DMS9BDQ	Asthma	CA23	Phase 2	[10]
RPL-554	DMLD4VQ	Allergic rhinitis	CA08.0	Phase 2	[11]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[12]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[15]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[14]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003767)
• [2] Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration
• [3] A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):11-26.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [6] In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology. 2003 Apr;98(4):944-9.
• [7] Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev. 2002 Fall;20(3):163-74.
• [8] Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8.
• [9] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [10] Company report (MediciNova)
• [11] Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.Lancet Respir Med.2013 Nov;1(9):714-27.
• [12] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [13] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [14] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [15] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [16] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [17] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [18] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.