Drug Information

Drug (ID: DG00175) and It's Reported Resistant Information

• Name: Capreomycin
• Synonyms: Capreomycin Sulfate Standard; Capreomycin sulphate; Caprocin (Disulfate); Ogostal (Disulfate); (3S)-3,6-diamino-N-[[(2S,5S,8E,11S,15S)-15-amino-11-[(6R)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-8-[(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentazacyclohexadec-5-yl]methyl]hexanamide; (3S)-3,6-diamino-N-[[(2S,5S,8E,11S,15S)-15-amino-11-[(6R)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-8-[(carbamoylamino)methylidene]-2-methyl-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentazacyclohexadec-5-yl]methyl]hexanamide
• Indication:
  In total 2 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
  Mycobacterium infection [ICD-11: 1B10-1B21]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Target: Bacterial 70S ribosomal RNA (Bact 70S rRNA); NOUNIPROTAC; [1]
• Formula: C50H88N28O15
• IsoSMILES: C[C@H]1C(=O)N[C@H](C(=O)N/C(=C/NC(=O)N)/C(=O)N[C@H](C(=O)NC[C@@H](C(=O)N1)N)[C@H]2CCN=C(N2)N)CNC(=O)C[C@H](CCCN)N.C1CN=C(N[C@H]1[C@H]2C(=O)NC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N/C(=C/NC(=O)N)/C(=O)N2)CNC(=O)C[C@H](CCCN)N)CO)N)N
• InChI: 1S/C25H44N14O8.C25H44N14O7/c26-4-1-2-11(27)6-17(41)32-8-14-20(43)35-15(9-34-25(30)47)21(44)39-18(13-3-5-31-24(29)38-13)23(46)33-7-12(28)19(42)37-16(10-40)22(45)36-14;1-11-19(41)36-15(9-32-17(40)7-12(27)3-2-5-26)21(43)37-16(10-34-25(30)46)22(44)39-18(14-4-6-31-24(29)38-14)23(45)33-8-13(28)20(42)35-11/h9,11-14,16,18,40H,1-8,10,26-28H2,(H,32,41)(H,33,46)(H,35,43)(H,36,45)(H,37,42)(H,39,44)(H3,29,31,38)(H3,30,34,47);10-15,18H,2-9,26-28H2,1H3,(H,32,40)(H,33,45)(H,35,42)(H,36,41)(H,37,43)(H,39,44)(H3,29,31,38)(H3,30,34,46)/b15-9+;16-10+/t11-,12-,13+,14-,16-,18-;11-,12-,13-,14+,15-,18-/m00/s1
• InChIKey: VCOPTHOUUNAYKQ-WBTCAYNUSA-N
• PubChem CID: 3000502
• TTD Drug ID: D0E7MV
• DrugBank ID: DB00314

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

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

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Capreomycin acetyltransferase (CPAA) [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; Inherence
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Paenibacillus sp. LC231; 1120679
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: CpaA inactivates capreomycin by acetylating the alpha-amino group of diaminopropionic acid at position 1.

Tuberculosis [ICD-11: 1B10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: CRISPR system Cms protein Csm4 (csm4) [2]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; K444R/E+N450D
• In Vitro Model: L6TG Cap cells; N.A.; Homo sapiens (Human); CVCL_C566
• Experiment for Drug Resistance: MIC assay; Time-Kill assay
• Mechanism Description: We found that, the?rv2820c?K114N mutation was highly enriched in CAP-resistant?Mtb?clinical isolates, especially in those isolates with the known CAP resistance conferring mutation?rrs?A1401G, implying the association of this mutation with the antimycobacterial efficacy of CAP. Subsequently, over-expressing the?rv2820c?K114N mutant was shown to increase the tolerance to CAP in?Ms, implying that the?rv2820c?K114N mutation might also confer tolerance to CAP in?Mtb?and be considered as a potential molecular marker for CAP tolerance in?Mtb?clinical isolates.

References

• Ref 1: A diverse intrinsic antibiotic resistome from a cave bacterium. Nat Commun. 2016 Dec 8;7:13803. doi: 10.1038/ncomms13803.
• Ref 2: The rv2820c K114N mutation is related with capreomycin tolerance. Tuberculosis (Edinb). 2024 Sep;148:102551.