Drug Information

Drug (ID: DG00678) and It's Reported Resistant Information

• Name: Ethambutol
• Synonyms: Ethambutol; 74-55-5; Ethambutolum; Aethambutolum; D-Ethambutol; (+)-S,S-Ethambutol; Ethambutol Hydrochloride; (+)-ethambutol; (S,S)-ethambutol; Myambutol; (2S,2'S)-2,2'-(Ethane-1,2-diylbis(azanediyl))bis(butan-1-ol); Etambutolo [DCIT]; Tibutol; Etambutol [INN-Spanish]; Ethambutolum [INN-Latin]; S,S-Ethambutol; Diambutol; Ebutol; CHEBI:4877; UNII-8G167061QZ; (+)-2,2'-(Ethylenediimino)di-1-butanol; Purderal; (+)-N,N'-Bis(1-(hydroxymethyl)propyl)ethylenediamine; EMB; (2S)-2-[2-[[(2S)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol; 8G167061QZ; (2R)-2-[2-(1-hydroxybutan-2-ylamino)ethylamino]butan-1-ol; 1-Butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (2S,2'S)-; 1-Butanol,2,2'-(1,2-ethanediyldiimino)bis-, (2S,2'S)-; (2S,7S)-2,7-diethyl-3,6-diazaoctane-1,8-diol; (2S,2'S)-2,2'-(ethane-1,2-diyldiimino)dibutan-1-ol; Etambutolo; C10H24N2O2; D-2,2'-(Ethylenediimino)di-1-butanol; D-2,2'-(Ethylenediimino)bis(1-butanol); 1-Butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (S-(R*,R*))-; Ethambutol, racemic mixture; 1-Butanol, 2,2'-(ethylenediimino)di-, (+)-; d,N,N'-Bis(1-hydroxymethylpropyl)ethylenediamine; D-N,N'-Bis(1-hydroxymethylpropyl)ethylenediamine; Ethambutol [INN:BAN]; (R)-2,2'-(1,2-Ethanediyldiimino)bis-1-butanol; NCGC00178864-03; 1-Butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (R-(R*,R*))-; HSDB 3078; Servambutol (TN); 95E; Ethambutol (INN); EINECS 200-810-6; Spectrum_001058; Spectrum2_001014; Spectrum3_000426; Spectrum4_000545; Spectrum5_000702; 1-Butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (R)-; Myambutol (dihydrochloride); SCHEMBL3399; BSPBio_002012; KBioGR_001209; KBioSS_001538; CHEMBL44884; DivK1c_000561; SPBio_001167; CL 40881 (dihydrochloride); DTXSID8023006; KBio1_000561; KBio2_001538; KBio2_004106; KBio2_006674; KBio3_001232; NINDS_000561; HY-B0535; 2860AH; BDBM50448407; ZINC19364219; DB00330; MCULE-9663372083; IDI1_000561; NCGC00178864-01; NCGC00178864-04; SBI-0051375.P003; C06984; D07925; D94801; E-3950; AB00053473_04; AB00053473_05; Q412318; (S,S)-2,2'-(1,2-Ethanediyldiimino)bis-1-butanol; BRD-K93231391-300-03-1; (+)-(S,S)-2,2'-(1,2-Ethylenediimino)-di-1-butanol; Ethambutol dihydrochloride, Antibiotic for Culture Media Use Only; (2S)-2-[(2-{[(2S)-1-hydroxybutan-2-yl]amino}ethyl)amino]butan-1-ol; (2S)-2-[2-[[(1S)-1-(hydroxymethyl)propyl]amino]ethylamino]butan-1-ol
• Indication:
  In total 1 Indication(s)
  Pulmonary tuberculosis [ICD-11: 1B10-1B12]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Inflammatory bowel diseases [ICD-11: DD72]; [2]
  Tuberculosis [ICD-11: 1B10]; [3]
  Tuberculous sclerokeratitis [ICD-11: 1B12]; [5]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Tuberculosis [ICD-11: 1B10]; [4]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Tuberculosis [ICD-11: 1B10]; [1]
• Target: Mycobacterium Arabinosyltransferase C (MycB embC); EMBC_MYCTU; [1]
• Formula: C10H24N2O2
• IsoSMILES: CC[C@@H](CO)NCCN[C@@H](CC)CO
• InChI: 1S/C10H24N2O2/c1-3-9(7-13)11-5-6-12-10(4-2)8-14/h9-14H,3-8H2,1-2H3/t9-,10-/m0/s1
• InChIKey: AEUTYOVWOVBAKS-UWVGGRQHSA-N
• PubChem CID: 14052
• ChEBI ID: CHEBI:4877
• TTD Drug ID: D08QME
• DrugBank ID: DB00330

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Tuberculosis [ICD-11: 1B10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Probable arabinosyltransferase A (EMBA) [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; .
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Mechanism Description: Ethambutol (EMB) is one of the first-line drugs regimens for TB treatment. Arabinosyl transferases are established targets of EMB, which is involved in the biosynthesis of arabinogalactan (AG) and lipoarabinomannan (LAM). Mutations among embCAB operon are responsible for around 70% clinical EMB resistant M. tuberculosis.

Key Molecule: Probable arabinosyltransferase B (EMBB) [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; .
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Mechanism Description: Ethambutol (EMB) is one of the first-line drugs regimens for TB treatment. Arabinosyl transferases are established targets of EMB, which is involved in the biosynthesis of arabinogalactan (AG) and lipoarabinomannan (LAM). Mutations among embCAB operon are responsible for around 70% clinical EMB resistant M. tuberculosis.

Key Molecule: Probable arabinosyltransferase C (EMBC) [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; .
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Mechanism Description: Ethambutol (EMB) is one of the first-line drugs regimens for TB treatment. Arabinosyl transferases are established targets of EMB, which is involved in the biosynthesis of arabinogalactan (AG) and lipoarabinomannan (LAM). Mutations among embCAB operon are responsible for around 70% clinical EMB resistant M. tuberculosis.

Key Molecule: Outer membrane protein A (OmpA) [4]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Expressiom; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Mycobacterium tuberculosis; 1773
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: These results support the model that the roles of OmpA as a porin protein overexpressing in mycobacteria can increase the hydrophilic ability of the cell wall which can facilitate the streptomycin uptakes and increase the mycobacteria's sensitivity to aminoglycosides.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Probable arabinosyltransferase B (EMBB) [6]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; R173C
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

References

• Ref 1: Mycobacterial ethambutol responsive genes and implications in antibiotics resistance .J Drug Target. 2021 Mar;29(3):284-293. doi: 10.1080/1061186X.2020.1853733. Epub 2020 Dec 3. 10.1080/1061186X.2020.1853733
• Ref 2: Drug resistance in inflammatory bowel diseases .Curr Opin Pharmacol. 2015 Dec;25:56-61. doi: 10.1016/j.coph.2015.11.003. Epub 2015 Nov 29. 10.1016/j.coph.2015.11.003
• Ref 3: Prevalence and patterns of drug resistance among pulmonary tuberculosis patients in Hangzhou, ChinaAntimicrob Resist Infect Control. 2018 May 2;7:61. doi: 10.1186/s13756-018-0348-7. eCollection 2018.
• Ref 4: Overexpression of outer membrane protein A (OmpA) increases aminoglycoside sensitivity in mycobacteria. BMC Microbiol. 2024 Nov 13;24(1):472.
• Ref 5: Tuberculous Scleritis and Multidrug ResistanceOcul Immunol Inflamm. 2021 Jan 8:1-10. doi: 10.1080/09273948.2020.1853176. Online ahead of print.
• Ref 6: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.