Drug Information

Drug (ID: DG00594) and It's Reported Resistant Information

• Name: Melamine-based arsenicals
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  African trypanosomiasis [ICD-11: 1F51]; [1]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

African trypanosomiasis [ICD-11: 1F51]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: NADH dehydrogenase [ubiquinone] flavoprotein 1 (TbAT1) [1]

• Resistant Disease: African trypanosomiasis [ICD-11: 1F51.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Trypanosoma brucei strain; 5691
• Mechanism Description: Reduced uptake and cross-resistance were apparently explained by the findings that melamine-based arsenicals and diamidines are imported into trypanosomes by the same transporter, and that this transporter is defective in drug-resistant cells. The transporter was called P2 (purine transporter 2) as its physiological substrates are adenine and adenosine, both of which compete with melarsoprol for uptake and can protect trypanosomes from melarsoprol-induced lysis.

References

• Ref 1: Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story .Trends Parasitol. 2013 Mar;29(3):110-8. doi: 10.1016/j.pt.2012.12.005. Epub 2013 Jan 30. 10.1016/j.pt.2012.12.005