Details of the Drug Combination

General Information of Drug Combination (ID: DC4CA4D)

Drug Combination Name
Nitazoxanide Doxycycline
Indication
Disease Entry Status REF
Sexually Transmitted Diseases Phase 2 [1]
Component Drugs Nitazoxanide   DMOWLVG Doxycycline   DM7ICNU
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Nitazoxanide
Disease Entry ICD 11 Status REF
Clostridioides difficile infection 1A04 Approved [2]
Cryptosporidium infection 1A32 Approved [2]
Diarrhea DA90 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Giardiasis N.A. Investigative [2]
Nitazoxanide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cryptosporidium Pyruvate:ferredoxin oxidoreductase (Crypto CpPNO) TT0F5P8 PNO_CRYPV Modulator [8]
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Nitazoxanide Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [9]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [10]
Eukaryotic translation initiation factor 2A (EIF2A) OTWXELQP EIF2A_HUMAN Increases Phosphorylation [9]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [11]
Dedicator of cytokinesis protein 8 (DOCK8) OTNQLL21 DOCK8_HUMAN Affects Response To Substance [11]
Slit homolog 3 protein (SLIT3) OTU8MKEU SLIT3_HUMAN Affects Response To Substance [11]
Sushi domain-containing protein 6 (SUSD6) OTZS4SKF SUSD6_HUMAN Affects Response To Substance [11]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Doxycycline
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Approved [5]
Actinomycosis N.A. Approved [5]
Acute gonococcal cervicitis N.A. Approved [5]
Acute gonococcal epididymo-orchitis N.A. Approved [5]
Advanced gum disease DA0D Approved [6]
Anthrax 1B97 Approved [5]
Bartonellosis N.A. Approved [5]
Boutonneuse fever N.A. Approved [5]
Brill-Zinsser disease N.A. Approved [5]
Bronchitis CA20 Approved [5]
Brucellosis N.A. Approved [5]
Chancroid N.A. Approved [5]
Chlamydiaceae infections N.A. Approved [5]
Chronic periodontitis DA0C.Y Approved [6]
Colorectal carcinoma N.A. Approved [5]
Cutaneous anthrax N.A. Approved [5]
Endemic typhus N.A. Approved [5]
Epidemic louse-borne typhus N.A. Approved [5]
Gastrointestinal anthrax N.A. Approved [5]
Inhalational anthrax N.A. Approved [5]
Listeriosis N.A. Approved [5]
Lymphogranuloma venereum N.A. Approved [5]
Mycoplasma pneumoniae pneumonia N.A. Approved [5]
Ornithosis N.A. Approved [5]
Q fever N.A. Approved [5]
Relapsing fever N.A. Approved [5]
Rickettsialpox N.A. Approved [5]
Rickettsiosis N.A. Approved [5]
Rocky mountain spotted fever N.A. Approved [5]
Syphilis N.A. Approved [5]
Trachoma N.A. Approved [5]
Tularemia 1B94 Approved [5]
Typhus N.A. Approved [5]
Yaws N.A. Approved [5]
Diabetic foot ulcer BD54 Phase 2 [7]
Sinusitis CA0A.Z Investigative [5]
Vibrio cholerae infection 1A00 Investigative [5]
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 [8]
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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 [13]
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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 [14]
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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 [15]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [12]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [12]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Affects Expression [16]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [17]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Activity [17]
Neutrophil collagenase (MMP8) OTZXH19L MMP8_HUMAN Decreases Activity [17]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Increases Expression [18]
TAR DNA-binding protein 43 (TARDBP) OTVOSFWW TADBP_HUMAN Decreases Expression [19]
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⏷ Show the Full List of 9 DOT(s)

References

1 ClinicalTrials.gov (NCT05897034) Combination Therapy Between Doxycycline, Pentoxifylline, and Nitazoxanide in Sexually Active Men
2 Nitazoxanide FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 ClinicalTrials.gov (NCT04382846) Novel Regimens in COVID-19 Treatment. U.S. National Institutes of Health.
5 Doxycycline FDA Label
6 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).
7 ClinicalTrials.gov (NCT00764361) Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers. U.S. National Institutes of Health.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 The anti-hepatitis C agent nitazoxanide induces phosphorylation of eukaryotic initiation factor 2alpha via protein kinase activated by double-stranded RNA activation. Gastroenterology. 2009 Nov;137(5):1827-35. doi: 10.1053/j.gastro.2009.07.056. Epub 2009 Aug 4.
10 Identification of Modulators That Activate the Constitutive Androstane Receptor From the Tox21 10K Compound Library. Toxicol Sci. 2019 Jan 1;167(1):282-292. doi: 10.1093/toxsci/kfy242.
11 Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.