Drug Information

Drug (ID: DG00261) and It's Reported Resistant Information

• Name: Doxycycline
• Synonyms: Atridox; Azudoxat; DOXY; Deoxymykoin; Dossiciclina; Doxiciclina; Doxitard; Doxivetin; Doxycen; Doxychel; Doxycin; Doxycyclin; Doxycyclinum; Doxysol; Doxytec; Doxytetracycline; Hydramycin; Investin; Jenacyclin; Liviatin; Monodox; Oracea; Ronaxan; Spanor; Supracyclin; Vibramycin; Vibramycine; Vibravenos; DOXCYCLINE ANHYDROUS; DOXYCYCLINE CALCIUM; DOXYCYCLINE MONOHYDRATE; Dossiciclina [DCIT]; Doxiciclina [Italian]; Doxycycline anhydrous; Doxycycline hyclate; Vibramycin Novum; Alpha-Doxycycline; Alti-Doxycycline; Apo-Doxy; BMY-28689; BU-3839T; Doxiciclina [INN-Spanish]; Doxy-Caps; Doxy-Puren; Doxy-Tabs; Doxychel (TN); Doxycycline (INN); Doxycycline (TN); Doxycycline (anhydrous); Doxycycline (internal use); Doxycycline-Chinoin; Doxycyclinum [INN-Latin]; Novo-Doxylin; Nu-Doxycycline; Periostat (TN); Vibra-tabs; Alpha-6-Deoxyoxytetracycline; DMSC (*Fosfatex); Doxycycline (200mg/day) or Placebo; Monodox (*monohydrate); Vibramycin (*monohydrate); Vivox (*Hyclate); GS-3065 (*monohydrate); Alpha-6-Deoxy-5-hydroxytetracycline; (2E,4S,4aR,5S,5aR,6R,12aS)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,10,11,12a-tetrahydroxy-6-methyl-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione; (2Z)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,10,11,12a-tetrahydroxy-6-methyl-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione; (2Z,4S,4aR,5S,5aR,6R)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,10,11,12a-tetrahydroxy-6-methyl-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione; (2Z,4S,4aR,5S,5aR,6R,12aS)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,10,11,12a-tetrahydroxy-6-methyl-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione; (4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide; 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, (4S,4aR,5S,5aR,6R,12aS); 5-Hydroxy-alpha-6-deoxytetracycline; 6-Deoxyoxytetracycline; 6-Deoxytetracycline; 6-alpha-Deoxy-5-oxytetracycline; 6alpha-Deoxy-5-oxytetracycline
• Indication:
  In total 3 Indication(s)
  Gingival/edentulous alveolar ridge disorder [ICD-11: DA0D]; Approved; [1]
  Periodontal disease [ICD-11: DA0C]; Approved; [1]
  Diabetic foot ulcer [ICD-11: BD54]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [2]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Pneumonia [ICD-11: CA40]; [3]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Campylobacteriosis [ICD-11: 1C40]; [4]
• Target: Bacterial 30S ribosomal RNA (Bact 30S rRNA); NOUNIPROTAC; [1]
• Formula: C22H24N2O8
• IsoSMILES: C[C@@H]1[C@H]2[C@@H]([C@H]3[C@@H](C(=O)C(=C([C@]3(C(=O)C2=C(C4=C1C=CC=C4O)O)O)O)C(=O)N)N(C)C)O
• InChI: 1S/C22H24N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-7,10,14-15,17,25-27,30,32H,1-3H3,(H2,23,31)/t7-,10+,14+,15-,17-,22-/m0/s1
• InChIKey: SGKRLCUYIXIAHR-AKNGSSGZSA-N
• PubChem CID: 54671203
• ChEBI ID: CHEBI:50845
• TTD Drug ID: D0S0LZ
• VARIDT ID: DR00666
• INTEDE ID: DR0547
• DrugBank ID: DB00254

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ARE-ABC-F family resistance factor PoxtA (POXTA) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• In Vitro Model: Enterococcus faecalis JH2-2; 1351
• In Vitro Model: Escherichia coli Mach1 T1R; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth dilution test assay
• Mechanism Description: The poxtA gene encodes a protein that is 32% identical to OptrA and exhibits structural features typical of the F lineage of the ATP-binding cassette (ABC) protein superfamily that cause antibiotic resistance by ribosomal protection.

Campylobacteriosis [ICD-11: 1C40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Ribosomal tetracycline resistance protein tet(44) (TET44) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Campylobacter fetus infection [ICD-11: 1C40.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli S17-1 Lambdapir; 1227813
• Experiment for Molecule Alteration: Illumina/Solexa sequencing assay
• Experiment for Drug Resistance: Broth microdilution assay
• Mechanism Description: The 640-amino-acid tetracycline resistance determinant, Tet 44, belongs to a class of proteins that confers resistance to tetracycline and minocycline by ribosomal protection.

Bacillus infection [ICD-11: 1C4Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

References

• Ref 1: Characterization of poxtA, a novel phenicol-oxazolidinone-tetracycline resistance gene from an MRSA of clinical origin. J Antimicrob Chemother. 2018 Jul 1;73(7):1763-1769. doi: 10.1093/jac/dky088.
• Ref 2: Identification of a new ribosomal protection type of tetracycline resistance gene, tet(36), from swine manure pits. Appl Environ Microbiol. 2003 Jul;69(7):4151-8. doi: 10.1128/AEM.69.7.4151-4158.2003.
• Ref 3: Ventilator-Associated Pneumonia and Its Responsible Germs; an Epidemiological Study .Emerg (Tehran). 2017;5(1):e26. Epub 2017 Jan 10.
• Ref 4: Two novel antibiotic resistance genes, tet(44) and ant(6)-Ib, are located within a transferable pathogenicity island in Campylobacter fetus subsp. fetus. Antimicrob Agents Chemother. 2010 Jul;54(7):3052-5. doi: 10.1128/AAC.00304-10. Epub 2010 May 17.