Drug Information

Drug (ID: DG00865) and It's Reported Resistant Information

• Name: Melarsoprol
• Synonyms: MELARSOPROL; 494-79-1; Mel B; Arsobal; Melarsoprolum [INN-Latin]; EINECS 207-793-4; RP 3854; CHEBI:6729; [2-[4-[(4,6-diamino-1,3,5-triazin-2-yl)amino]phenyl]-1,3,2-dithiarsolan-4-yl]methanol; RP-3854; Melarsoprolum; (2-(4-((4,6-diamino-1,3,5-triazin-2-yl)amino)phenyl)-1,3,2-dithiarsolan-4-yl)methanol; (2-{4-[(4,6-diamino-1,3,5-triazin-2-yl)amino]phenyl}-1,3,2-dithiarsolan-4-yl)methanol; Melarsoprol [INN:BAN:DCF]; Specia; UNII-ZF3786Q2E8; Melarsoprol (INN); Mel B (TN); CHEMBL166; 1,3,2-Dithiarsolane-4-methanol, 2-(4-((4,6-diamino-1,3,5-triazin-2-yl)amino)phenyl)-; SCHEMBL61707; DTXSID90862033; ZF3786Q2E8; DB12864; 2-(p-(4,6-Diamino-s-triazin-2-ylamino)phenyl)-1,3,2-dithiarsolane-4-methanol; C08001; D00832; Q419753; 2-[4-{(4,6-Diamino-1,3,5-triazin-2-yl)amino}phenyl]-1,3,2-dithiarsolan-e-4-methanol
• Indication:
  In total 1 Indication(s)
  Trypanosomiasis [ICD-11: 1D51-1F53]; Approved; [1]
• 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]
• Target: Cysteine protease (CYP); NOUNIPROTAC; [1]
• Formula: C12H15AsN6OS2
• IsoSMILES: C1C(S[As](S1)C2=CC=C(C=C2)NC3=NC(=NC(=N3)N)N)CO
• InChI: 1S/C12H15AsN6OS2/c14-10-17-11(15)19-12(18-10)16-8-3-1-7(2-4-8)13-21-6-9(5-20)22-13/h1-4,9,20H,5-6H2,(H5,14,15,16,17,18,19)
• InChIKey: JCYZMTMYPZHVBF-UHFFFAOYSA-N
• PubChem CID: 10311
• ChEBI ID: CHEBI:6729
• TTD Drug ID: D06HCP
• DrugBank ID: DB12864

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

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

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Aquaporin 2 (AQP2) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: African trypanosomiasis [ICD-11: 1F51.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: African trypanosomiasis strain; N.A.
• Mechanism Description: The laboratory studies above showed that uptake of both melarsoprol and pentamidine by trypanosomes is under the control of both the P2 adenosine transporter and AQP2. These studies were extended to additional T. b. brucei, T. b. gambiense, and T. b. rhodesiense cross-resistant laboratory-selected strains, which all revealed either chimeric AQP2/3 genes or complete loss of AQP2.

Key Molecule: Aquaporin 2/3 (AQP2/3) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: African trypanosomiasis [ICD-11: 1F51.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: African trypanosomiasis strain; N.A.
• Mechanism Description: The laboratory studies above showed that uptake of both melarsoprol and pentamidine by trypanosomes is under the control of both the P2 adenosine transporter and AQP2. These studies were extended to additional T. b. brucei, T. b. gambiense, and T. b. rhodesiense cross-resistant laboratory-selected strains, which all revealed either chimeric AQP2/3 genes or complete loss of AQP2.

References

• Ref 1: Melarsoprol Resistance in African Trypanosomiasis .Trends Parasitol. 2018 Jun;34(6):481-492. doi: 10.1016/j.pt.2018.04.002. Epub 2018 Apr 25. 10.1016/j.pt.2018.04.002