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

General Information of Drug (ID: DM6W8V5)

• Drug Name: Lisdexamfetamine Drug Info
• Synonyms: NRP104; Lisdexamfetamine (INN); Vyvanse (TN)

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]
Binge eating disorder		Approved	[2]

• Cross-matching ID:
  PubChem CID: 11597698
  ChEBI ID: CHEBI:135925
  CAS Number: CAS 608137-32-2
  TTD Drug ID: DM6W8V5
  VARIDT Drug ID: DR00003
  INTEDE Drug ID: DR0963
  ACDINA Drug ID: D00369

Molecule-Related Drug Atlas

Drug(s) Targeting Trace amine-associated receptor-1 (TAAR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amphetamine	DMSZQAK	Attention deficit hyperactivity disorder	6A05.Z	Approved	[6]
Dextroamphetamine	DMMIHVP	Attention deficit hyperactivity disorder	6A05.Z	Approved	[6]
Hydroxyamphetamine Hydrobromide	DMQSGM0	Horner syndrome	8D8A.1	Approved	[7]
SEP-363856	DMG2QP4	Schizophrenia	6A20	Phase 3	[8]
NT0202	DMCMIJ1	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[6]
SPD-465	DM7NV1I	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[6]
RG-7351	DMFGR98	Major depressive disorder	6A70.3	Phase 1	[9]
tyramine	DM4UXT1	Discovery agent	N.A.	Investigative	[10]
EPPTB	DMK3VID	Discovery agent	N.A.	Investigative	[11]
R(-)amphetamine	DM72ES1	Discovery agent	N.A.	Investigative	[12]

Drug(s) Transported By Peptide transporter 1 (SLC15A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[13]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[14]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[15]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[16]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[17]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[18]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[19]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[14]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[16]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[16]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[20]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[25]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[26]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[27]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[28]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Trace amine-associated receptor-1 (TAAR1)	TTIU98M	TAAR1_HUMAN	Modulator	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[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: 7213).
• [2] Lisdexamfetamine FDA Label
• [3] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [4] Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine. Neuropsychiatr Dis Treat. 2010 Jun 24;6:317-27.
• [5] Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug. Neuropharmacology. 2014 Dec;87:41-50.
• [6] Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology. 2014 Oct;85:499-507.
• [7] Diagnostic pharmacology of the pupil.Clin Neuropharmacol.1985;8(1):27-37.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Clinical pipeline report, company report or official report of Roche.
• [10] Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists. PLoS One. 2011;6(10):e27073.
• [11] The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20081-6.
• [12] The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav. 2007 Oct;6(7):628-39.
• [13] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [14] Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
• [15] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [16] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [17] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [18] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [19] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [20] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [21] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [22] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [23] 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.
• [24] 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.
• [25] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [26] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [27] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [28] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [29] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.