Details of the Drug Combination

General Information of Drug Combination (ID: DCKI84K)

• Drug Combination Name: Tindamax + Doxycycline
• Indication: Urethritis; Status: Phase 1 [1]
• Component Drugs:
  Tindamax (DM3OWT4): Small molecular drug
  Doxycycline (DM7ICNU): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tindamax

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Bacterial vaginosis	MF3A	Approved	[3]
Trichomoniasis	N.A.	Approved	[4]
Giardiasis	N.A.	Investigative	[5]

Tindamax Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Nitroreductase (NTR)	DEAN5EW	NFSB_ENTCL	Metabolism	[10]

Tindamax Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[11]

Indication(s) of Doxycycline

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[6]
Actinomycosis	N.A.	Approved	[6]
Acute gonococcal cervicitis	N.A.	Approved	[6]
Acute gonococcal epididymo-orchitis	N.A.	Approved	[6]
Advanced gum disease	DA0D	Approved	[7]
Anthrax	1B97	Approved	[6]
Bartonellosis	N.A.	Approved	[6]
Boutonneuse fever	N.A.	Approved	[6]
Brill-Zinsser disease	N.A.	Approved	[6]
Bronchitis	CA20	Approved	[6]
Brucellosis	N.A.	Approved	[6]
Chancroid	N.A.	Approved	[6]
Chlamydiaceae infections	N.A.	Approved	[6]
Chronic periodontitis	DA0C.Y	Approved	[7]
Colorectal carcinoma	N.A.	Approved	[6]
Cutaneous anthrax	N.A.	Approved	[6]
Endemic typhus	N.A.	Approved	[6]
Epidemic louse-borne typhus	N.A.	Approved	[6]
Gastrointestinal anthrax	N.A.	Approved	[6]
Inhalational anthrax	N.A.	Approved	[6]
Listeriosis	N.A.	Approved	[6]
Lymphogranuloma venereum	N.A.	Approved	[6]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[6]
Ornithosis	N.A.	Approved	[6]
Q fever	N.A.	Approved	[6]
Relapsing fever	N.A.	Approved	[6]
Rickettsialpox	N.A.	Approved	[6]
Rickettsiosis	N.A.	Approved	[6]
Rocky mountain spotted fever	N.A.	Approved	[6]
Syphilis	N.A.	Approved	[6]
Trachoma	N.A.	Approved	[6]
Tularemia	1B94	Approved	[6]
Typhus	N.A.	Approved	[6]
Yaws	N.A.	Approved	[6]
Diabetic foot ulcer	BD54	Phase 2	[8]
Sinusitis	CA0A.Z	Investigative	[6]
Vibrio cholerae infection	1A00	Investigative	[6]

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	[13]

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	[14]

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	[15]

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	[16]
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	[17]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Activity	[18]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Decreases Activity	[18]
Neutrophil collagenase (MMP8)	OTZXH19L	MMP8_HUMAN	Decreases Activity	[18]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[19]
TAR DNA-binding protein 43 (TARDBP)	OTVOSFWW	TADBP_HUMAN	Decreases Expression	[20]

References

• [1] ClinicalTrials.gov (NCT00322465) NGU: Doxycycline (Plus or Minus Tinidazole) Versus Azithromycin (Plus or Minus Tinidazole)
• [2] 2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.
• [3] Tinidazole. 2021 Mar 17. Drugs and Lactation Database (LactMed?) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006C.
• [4] Tinidazole (Tindamax)--a new option for treatment of bacterial vaginosis. Med Lett Drugs Ther. 2007 Sep 10;49(1269):73-4.
• [5] Tinidazole (Tindamax) - a new anti-protozoal drug. Med Lett Drugs Ther. 2004 Aug 30;46(1190):70-2.
• [6] Doxycycline FDA Label
• [7] 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).
• [8] ClinicalTrials.gov (NCT00764361) Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers. U.S. National Institutes of Health.
• [9] FDA label of Tinidazole. The 2020 official website of the U.S. Food and Drug Administration.
• [10] Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif. 1998 Jun;13(1):53-60.
• [11] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [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] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.