General Information of Drug Combination (ID: DC12XST)

Drug Combination Name
Doxycycline Piperaquine
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Doxycycline   DM7ICNU Piperaquine   DMT70RC
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 2.948
Bliss Independence Score: 1.526
Loewe Additivity Score: 5.676
LHighest Single Agent (HSA) Score: 7.873

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Doxycycline
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Approved [2]
Actinomycosis N.A. Approved [2]
Acute gonococcal cervicitis N.A. Approved [2]
Acute gonococcal epididymo-orchitis N.A. Approved [2]
Advanced gum disease DA0D Approved [3]
Anthrax 1B97 Approved [2]
Bartonellosis N.A. Approved [2]
Boutonneuse fever N.A. Approved [2]
Brill-Zinsser disease N.A. Approved [2]
Bronchitis CA20 Approved [2]
Brucellosis N.A. Approved [2]
Chancroid N.A. Approved [2]
Chlamydiaceae infections N.A. Approved [2]
Chronic periodontitis DA0C.Y Approved [3]
Colorectal carcinoma N.A. Approved [2]
Cutaneous anthrax N.A. Approved [2]
Endemic typhus N.A. Approved [2]
Epidemic louse-borne typhus N.A. Approved [2]
Gastrointestinal anthrax N.A. Approved [2]
Inhalational anthrax N.A. Approved [2]
Listeriosis N.A. Approved [2]
Lymphogranuloma venereum N.A. Approved [2]
Mycoplasma pneumoniae pneumonia N.A. Approved [2]
Ornithosis N.A. Approved [2]
Q fever N.A. Approved [2]
Relapsing fever N.A. Approved [2]
Rickettsialpox N.A. Approved [2]
Rickettsiosis N.A. Approved [2]
Rocky mountain spotted fever N.A. Approved [2]
Syphilis N.A. Approved [2]
Trachoma N.A. Approved [2]
Tularemia 1B94 Approved [2]
Typhus N.A. Approved [2]
Yaws N.A. Approved [2]
Diabetic foot ulcer BD54 Phase 2 [4]
Sinusitis CA0A.Z Investigative [2]
Vibrio cholerae infection 1A00 Investigative [2]
Doxycycline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA) TTOVFH2 NOUNIPROTAC Modulator [7]
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Doxycycline Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Doxycycline Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
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Doxycycline Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [10]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [6]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [6]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Affects Expression [11]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [12]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Activity [12]
Neutrophil collagenase (MMP8) OTZXH19L MMP8_HUMAN Decreases Activity [12]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Increases Expression [13]
TAR DNA-binding protein 43 (TARDBP) OTVOSFWW TADBP_HUMAN Decreases Expression [14]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Piperaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [5]
Piperaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [5]
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Piperaquine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [15]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [16]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Doxycycline FDA Label
3 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: 6464).
4 ClinicalTrials.gov (NCT00764361) Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers. U.S. National Institutes of Health.
5 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
6 Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):293-301.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 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.
9 A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition. Eur J Drug Metab Pharmacokinet. 1999 Jul-Sep;24(3):272-8.
10 Functional and histochemical analysis of MDR3 P-glycoprotein in a tetracycline-controlled gene expression system. Eur J Med Res. 2000 Dec 29;5(12):517-22.
11 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
12 Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg Med Chem. 2007 Mar 15;15(6):2368-74. doi: 10.1016/j.bmc.2007.01.026. Epub 2007 Jan 19.
13 Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol Sci. 2010 Jul;116(1):140-50. doi: 10.1093/toxsci/kfq085. Epub 2010 Mar 25.
14 A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity. J Biomol Screen. 2014 Jan;19(1):44-56. doi: 10.1177/1087057113501553. Epub 2013 Sep 9.
15 Eurartesim - European Medicines Agency
16 Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult thai subjects. Antimicrob Agents Chemother. 2014 Dec;58(12):7340-6.