Details of the Drug Combination

General Information of Drug Combination (ID: DC3SWUO)

Drug Combination Name
Doxycycline Benzylpenicillin
Indication
Disease Entry Status REF
Early Syphilis Phase 4 [1]
Component Drugs Doxycycline   DM7ICNU Benzylpenicillin   DMS9503
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 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 [44]
------------------------------------------------------------------------------------
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 [45]
------------------------------------------------------------------------------------
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 [46]
------------------------------------------------------------------------------------
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 [47]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [43]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [43]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Affects Expression [48]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [49]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Activity [49]
Neutrophil collagenase (MMP8) OTZXH19L MMP8_HUMAN Decreases Activity [49]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Increases Expression [50]
TAR DNA-binding protein 43 (TARDBP) OTVOSFWW TADBP_HUMAN Decreases Expression [51]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 DOT(s)
Indication(s) of Benzylpenicillin
Disease Entry ICD 11 Status REF
Actinomycosis N.A. Approved [5]
Acute otitis media AB00 Approved [6]
Anthrax 1B97 Approved [7]
Bacterial endocarditis N.A. Approved [8]
Botulism 1A11 Approved [9]
Cervicofacial actinomycosis N.A. Approved [10]
Congenital syphilis N.A. Approved [11]
Cutaneous anthrax N.A. Approved [12]
Erysipelas N.A. Approved [13]
Erysipelothrix rhusiopathiae infectious disease N.A. Approved [14]
Gastrointestinal anthrax N.A. Approved [15]
Gonococcal infection of joint N.A. Approved [16]
Inhalational anthrax N.A. Approved [7]
Late latent syphilis N.A. Approved [17]
Latent syphilis N.A. Approved [18]
Latent yaws N.A. Approved [19]
Listeria meningitis N.A. Approved [20]
Lung abscess N.A. Approved [21]
Meningococcal meningitis N.A. Approved [22]
Meningococcemia N.A. Approved [23]
Neonatal sepsis N.A. Approved [24]
Neurosyphilis N.A. Approved [25]
Pasteurella multocida infectious disease N.A. Approved [26]
Pasteurellosis N.A. Approved [27]
Pneumococcal meningitis N.A. Approved [20]
Psoriasis EA90 Approved [28]
Rat-bite fever N.A. Approved [29]
Respiratory tract infection CA45 Approved [30]
Staphylococcus aureus infection N.A. Approved [31]
Streptococcal pneumonia N.A. Approved [32]
Streptococcal toxic-shock syndrome N.A. Approved [33]
Streptococcus infection 1B53 Approved [34]
Syphilis N.A. Approved [35]
Tertiary lesion of yaws N.A. Approved [36]
Yaws N.A. Approved [37]
Bejel N.A. Investigative [38]
Latent early syphilis N.A. Investigative [39]
Secondary syphilis N.A. Investigative [40]
Tertiary syphilis N.A. Investigative [41]
Tetanus 1C13 Investigative [42]
Benzylpenicillin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Penicillin binding protein 3 (Bact mrcA) TT85JMW FTSI_ECOLI Binder [53]
Bacterial Penicillin binding protein 1 (Bact pbp) TTTKCMH PBPA_ECOLI; PBPB_ECOLI; PBPC_ECOLI Binder [54]
------------------------------------------------------------------------------------
Benzylpenicillin Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [55]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [56]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [57]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [58]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [59]
Organic anion transporting polypeptide 3A1 (SLCO3A1) DTVNRXW SO3A1_HUMAN Substrate [59]
Organic anion transporting polypeptide 4A1 (SLCO4A1) DT8H2IC SO4A1_HUMAN Substrate [59]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DTP(s)
Benzylpenicillin Interacts with 11 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Beta-lactamase (blaB) DEV0KWQ Q8KT52_9BACT Metabolism [60]
N-acylhomoserine lactone acylase (lacA) DEIU0XN A0A0A1VBK6_9BURK Metabolism [61]
Beta-lactamase (blaB) DET9I1W BLAC_BACUN Metabolism [62]
Beta-lactamase (blaB) DENJ2SQ BLAB_BACFG Metabolism [60]
Beta-lactamase (blaB) DESIWFO Q8GQK7_9FLAO Metabolism [63]
Beta-lactamase (blaB) DEQX0DG Q8RIK5_FUSNN Metabolism [64]
Beta-lactamase (blaB) DE37FJH C6JIU1_FUSVA Metabolism [60]
Beta-lactamase (blaB) DEAILCM A0A246EJV2_9BACT Metabolism [65]
Beta-lactamase (blaB) DERPJ4F A0A2S8IKB0_BURCE Metabolism [66]
Beta-lactamase (blaB) DEBAZ7H F9DGI4_9BACT Metabolism [65]
Beta-lactamase (blaB) DEA5OYT A0A4U8WDG3_9FLAO Metabolism [67]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 DME(s)
Benzylpenicillin Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Uptake [68]
Pirin (PIR) OT8ALXHU PIR_HUMAN Increases Expression [69]
Tripartite motif-containing protein 16 (TRIM16) OTLRXYOZ TRI16_HUMAN Increases Expression [69]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [69]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [69]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Increases Expression [69]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [69]
Insulin-like growth factor II (IGF2) OTJ4O6MW IGF2_HUMAN Decreases Expression [52]
Alpha-fetoprotein (AFP) OT9GG3ZI FETA_HUMAN Decreases Expression [52]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Expression [52]
Decorin (DCN) OTWLJL7K PGS2_HUMAN Decreases Expression [52]
Annexin A8 (ANXA8) OTLSSQCY ANXA8_HUMAN Decreases Expression [52]
Insulin-like growth factor-binding protein 5 (IGFBP5) OTRE5V0C IBP5_HUMAN Decreases Expression [52]
Secreted frizzled-related protein 3 (FRZB) OTTO3DPY SFRP3_HUMAN Decreases Expression [52]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [70]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3) OTC1UOHP ATF3_HUMAN Increases Expression [70]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Increases Expression [71]
Interleukin-18 (IL18) OTBB2A8O IL18_HUMAN Increases Expression [72]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [73]
------------------------------------------------------------------------------------
⏷ Show the Full List of 19 DOT(s)

References

1 ClinicalTrials.gov (NCT05980871) Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline
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 Abdominal actinomycosis after reparative surgery for cholecystogastric fistula in an immunosuppressed patient. BMJ Case Rep. 2021 Jul 23;14(7):e243445.
6 Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates from children with acute otitis media in Japan from 2014 to 2017. J Infect Chemother. 2019 Mar;25(3):229-232.
7 Human Anthrax: Update of the Diagnosis and Treatment. Diagnostics (Basel). 2023 Mar 10;13(6):1056.
8 Optimisation of the prevention and treatment of bacterial endocarditis. Drugs Aging. 2001;18(6):415-24.
9 Clinical Serum Therapy: Benefits, Cautions, and Potential Applications. Keio J Med. 2017 Dec 25;66(4):57-64.
10 Cervicofacial actinomycosis: a report of 14 patients observed at the Dermatology Unit of the University of Milan, Italy. Int J Dermatol. 2020 Oct;59(10):1222-1225.
11 Congenital syphilis in a preterm newborn with gastrointestinal disorders and postnatal growth restriction. Ital J Pediatr. 2022 Dec 29;48(1):205.
12 Cutaneous Anthrax. J Emerg Med. 2017 Feb;52(2):240-241.
13 [Streptococcus pyogenes--much more than the aetiological agent of scarlet fever]. Med Monatsschr Pharm. 2009 Nov;32(11):408-16; quiz 417-8.
14 Erysipelothrix rhusiopathiae bloodstream infection - A 22-year experience at Mayo Clinic, Minnesota. Zoonoses Public Health. 2017 Nov;64(7):e65-e72.
15 Inhalational, gastrointestinal, and cutaneous anthrax in children: a systematic review of cases: 1900 to 2005. Arch Pediatr Adolesc Med. 2007 Sep;161(9):896-905.
16 Infectious arthritis. Infect Dis Clin North Am. 1990 Sep;4(3):523-38.
17 Syphilis. Lancet. 2023 Jul 22;402(10398):336-346.
18 Diagnosis, treatment, and notification of syphilis during pregnancy in the state of Gois, Brazil, between 2007 and 2017. Rev Saude Publica. 2021 Oct 29;55:68.
19 Yaws. 2023 Jul 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 JanC.
20 Meningitis in adults: diagnosis and management. Intern Med J. 2018 Nov;48(11):1294-1307.
21 Spontaneous Clostridium perfringens lung abscess unresponsive to penicillin. Anaesth Intensive Care. 1993 Feb;21(1):117-9.
22 Meningococcal meningitis and diabetes insipidus. Scand J Infect Dis. 1988;20(3):341-3.
23 [An unusual cause of fever: chronic meningococcemia]. Ned Tijdschr Geneeskd. 1996 Apr 6;140(14):785-7.
24 Antibiotic regimens for early-onset neonatal sepsis. Cochrane Database Syst Rev. 2021 May 17;5(5):CD013837.
25 Ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis in France: a retrospective multicentre study. Lancet Infect Dis. 2021 Oct;21(10):1441-1447.
26 Pasteurella multocida pneumonia. Semin Respir Infect. 1997 Mar;12(1):54-6.
27 Pasteurella Multocida. 2023 May 16. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 JanC.
28 A review of antibiotics and psoriasis: induction, exacerbation, and amelioration. Expert Rev Clin Pharmacol. 2019 Oct;12(10):981-989.
29 Rat-Bite Fever. 2023 Mar 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 JanC.
30 Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical treatment of Haemophilus influenzae-associated lower respiratory tract infections in adults; a retrospective propensity score-matched study. Eur J Clin Microbiol Infect Dis. 2018 Sep;37(9):1761-1775.
31 In vivo synergy between 6 beta-amidinopenicillanic acid derivatives and other antibiotics. Antimicrob Agents Chemother. 1976 Apr;9(4):589-94.
32 Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet. 2009 Oct 31;374(9700):1543-56.
33 [Beta-hemolytic streptococcal bacteremia in adults]. Duodecim. 2013;129(14):1477-84.
34 Prevalence and treatment of group B streptococcus colonization based on risk factors versus intrapartum culture screening. Eur J Obstet Gynecol Reprod Biol. 2019 Sep;240:178-181.
35 Diagnosis and treatment of syphilis in pregnant women at the services of Primary Care. Cien Saude Colet. 2022 Aug;27(8):3331-3340.
36 A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
37 Yaws Osteoperiostitis Treated with Single-Dose Azithromycin. Am J Trop Med Hyg. 2017 May;96(5):1039-1041.
38 2020 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol. 2021 Mar;35(3):574-588.
39 Syphilis. Enferm Infecc Microbiol Clin (Engl Ed). 2019 Jun-Jul;37(6):398-404.
40 Secondary Syphilis. Clin Pract Cases Emerg Med. 2020 Nov;4(4):675-676.
41 A rare case of tertiary syphilis spondylodiscitis of the upper cervical spine: Diagnostic and therapeutic complexity, review of literature. Orthop Rev (Pavia). 2020 Jun 25;12(Suppl 1):8675.
42 Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial. Ann Trop Med Parasitol. 2004 Jan;98(1):59-63.
43 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.
44 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
45 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.
46 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.
47 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.
48 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.
49 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.
50 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.
51 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.
52 Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
53 Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother. 2001 Jun;45(6):1693-9.
54 Overexpression, purification and biochemical characterization of a class A high-molecular-mass penicillin-binding protein (PBP), PBP1* and its soluble derivative from Mycobacterium tuberculosis. Biochem J. 2002 Feb 1;361(Pt 3):635-9.
55 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
56 Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev. 2006 Nov 15;58(11):1136-63.
57 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
58 Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Toxicol Sci. 2006 May;91(1):140-9.
59 Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.
60 Antimicrobial drugs used in the management of anaerobic infections in children. Drugs. 1983 Dec;26(6):520-9.
61 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.
62 Purification and characterization of a new beta-lactamase from Bacteroides uniformis. Antimicrob Agents Chemother. 1995 Jul;39(7):1458-61.
63 EBR-1, a novel Ambler subclass B1 beta-lactamase from Empedobacter brevis. Antimicrob Agents Chemother. 2002 Oct;46(10):3223-7.
64 beta-lactamase production and antimicrobial susceptibility of oral heterogeneous Fusobacterium nucleatum populations in young children. Antimicrob Agents Chemother. 1999 May;43(5):1270-3.
65 Beta-lactamase production in Prevotella intermedia, Prevotella nigrescens, and Prevotella pallens genotypes and in vitro susceptibilities to selected antimicrobial agents. Antimicrob Agents Chemother. 1999 Oct;43(10):2383-8.
66 Characterization of the penA and penR genes of Burkholderia cepacia 249 which encode the chromosomal class A penicillinase and its LysR-type transcriptional regulator. Antimicrob Agents Chemother. 1997 Nov;41(11):2399-405.
67 Genetic and biochemical characterization of CGB-1, an Ambler class B carbapenem-hydrolyzing beta-lactamase from Chryseobacterium gleum. Antimicrob Agents Chemother. 2002 Sep;46(9):2791-6.
68 Characterization of the uptake of organic anion transporter (OAT) 1 and OAT3 substrates by human kidney slices. J Pharmacol Exp Ther. 2007 Apr;321(1):362-9. doi: 10.1124/jpet.106.113076. Epub 2007 Jan 25.
69 Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte-derived dendritic cells. Toxicol Appl Pharmacol. 2012 Aug 1;262(3):283-92.
70 An in vitro skin sensitization assay termed EpiSensA for broad sets of chemicals including lipophilic chemicals and pre/pro-haptens. Toxicol In Vitro. 2017 Apr;40:11-25. doi: 10.1016/j.tiv.2016.12.005. Epub 2016 Dec 10.
71 A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals. Toxicology. 2009 Oct 1;264(1-2):1-9. doi: 10.1016/j.tox.2009.07.021. Epub 2009 Aug 7.
72 NCTC 2544 and IL-18 production: a tool for the identification of contact allergens. Toxicol In Vitro. 2013 Apr;27(3):1127-34. doi: 10.1016/j.tiv.2012.05.018. Epub 2012 Oct 9.
73 Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.