Details of the Drug Combination

General Information of Drug Combination (ID: DC8MZW4)

• Drug Combination Name: Doxycycline + Cephalexin
• Indication: Infections Joint Prosthetic; Status: Phase 4 [1]
• Component Drugs:
  Doxycycline (DM7ICNU): Small molecular drug
  Cephalexin (DMD5JU8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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	[8]

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	[9]

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	[10]

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	[11]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Increases Expression	[7]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[7]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[12]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Activity	[13]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Decreases Activity	[13]
Neutrophil collagenase (MMP8)	OTZXH19L	MMP8_HUMAN	Decreases Activity	[13]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[14]
TAR DNA-binding protein 43 (TARDBP)	OTVOSFWW	TADBP_HUMAN	Decreases Expression	[15]

Indication(s) of Cephalexin

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[5]
Bacterial infection	1A00-1C4Z	Approved	[6]
Prostatitis	N.A.	Approved	[5]
Staphylococcus aureus infection	N.A.	Approved	[5]

Cephalexin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[16]

Cephalexin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[17]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[18]
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[19]

Cephalexin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[21]
N-acylhomoserine lactone acylase (lacA)	DEIU0XN	A0A0A1VBK6_9BURK	Metabolism	[22]

Cephalexin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[12]

References

• [1] ClinicalTrials.gov (NCT04297592) Antibiotic Prophylaxis in High-Risk Arthroplasty Patients
• [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] Cephalexin 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: 4832).
• [7] 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.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [17] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
• [18] Direct evidence for efficient transport and minimal metabolism of L-cephalexin by oligopeptide transporter 1 in budded baculovirus fraction. Biol Pharm Bull. 2009 Aug;32(8):1459-61.
• [19] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [20] Transport and metabolic characterization of Caco-2 cells expressing CYP3A4 and CYP3A4 plus oxidoreductase. Pharm Res. 1999 Sep;16(9):1352-9.
• [21] Population pharmacokinetic analysis of mirtazapine. Eur J Clin Pharmacol. 2004 Sep;60(7):473-80.
• [22] A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl Environ Microbiol. 2017 Jun 16;83(13). pii: e00080-17.