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

General Information of Drug (ID: DMT70RC)

• Drug Name: Piperaquine Drug Info
• Synonyms: Piperaquinoline; Quinoline, 4,4'-(1,3-propanediyldi-4,1-piperazinediyl)bis(7-chloro-); Quinoline, 4,4'-(1,3-propanediyldi-4,1-piperazinediyl)bis(7-chloro-(9CI); 1,3-bis(1-(7-chloro-4'-quinolyl)-4'-piperazinyl)propane; 1,3-bis(4-(7'-chloro-4'-quinoline)-1-piperazine); 4,4'-(propane-1,3-diyldipiperazine-4,1-diyl)bis(7-chloroquinoline); 7-chloro-4-[4-[3-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]propyl]piperazin-1-yl]quinoline

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[1]

• Cross-matching ID:
  PubChem CID: 122262
  ChEBI ID: CHEBI:91231
  CAS Number: CAS 4085-31-8
  TTD Drug ID: DMT70RC
  INTEDE Drug ID: DR1296

Molecule-Related Drug Atlas

Drug(s) Targeting Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Artemisinin	DMOY7W3	Malaria	1F40-1F45	Approved	[1]
Dihydroartemisinin	DMBXVMZ	Malaria	1F40-1F45	Approved	[1]
Artemisinin SP	DMFETDK	Malaria	1F40-1F45	Approved	[1]
Artesunate	DMR27C8	Infection of P. falciparum	1F40	Approved	[1]
OZ277	DM1YB0R	Malaria	1F40-1F45	Approved	[1]
Pyronaridine	DMUWAM2	Malaria	1F40-1F45	Approved	[1]
Vanadate	DMQL0KF	Psoriatic arthritis	FA21	Phase 3	[4]
THAPSIGARGIN	DMDMQIE	N. A.	N. A.	Preclinical	[5]
Cyclopiazonic acid	DMPJ08G	Discovery agent	N.A.	Investigative	[4]

Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[6]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[8]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[9]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[9]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[11]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[12]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[13]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[14]

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	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[6]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[9]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[18]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[14]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[20]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)	TTZVSJ2	NOUNIPROTAC	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[2]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[3]

References

• [1] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [2] Eurartesim - European Medicines Agency
• [3] Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult thai subjects. Antimicrob Agents Chemother. 2014 Dec;58(12):7340-6.
• [4] Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms. J Biol Chem. 2001 Apr 6;276(14):10782-7.
• [5] Elucidation of the topography of the thapsigargin binding site in the sarco-endoplasmic calcium ATPase. Bioorg Med Chem. 2010 Aug 1;18(15):5634-46.
• [6] 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.
• [7] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [8] Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
• [9] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [10] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [11] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [12] New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
• [13] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [14] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [15] 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.
• [16] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [17] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.