Open main menu

Fexinidazole is an antiprotozoal agent.[1] It has activity against Trypanosoma cruzi, Tritrichomonas foetus, Trichomonas vaginalis, Entamoeba histolytica,[1] Trypanosoma brucei,[2] and Leishmania donovani.[3] The biologically relevant active metabolites in vivo are the sulfoxide and sulfone.[3][4] Fexinidazole was discovered by the German pharmaceutical company Hoechst AG, but its development as a pharmaceutical was halted in the 1980s.[5] Fexinidazole is now being studied through a collaboration between Sanofi and the Drugs for Neglected Diseases Initiative (DNDi) for the treatment of Chagas disease and human African trypanosomiasis (sleeping sickness).[6][7] Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years.[8]

Fexinidazole
Fexinidazole.svg
Names
IUPAC name
1-Methyl-2-{[4-(methylsulfanyl)phenoxy]methyl}-5-nitro-1H-imidazole
Other names
HOE 239
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.207.619
KEGG
UNII
Properties
C12H13N3O3S
Molar mass 279.31 g·mol−1
Pharmacology
P01CA03 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

A clinical trial in the Democratic Republic of the Congo and the Central African Republic concluded that fexinidazole had a 91.2 success rate at treating sleeping sickness, 18 months after treatment; these results were published in the Lancet in 2017.[9]

Fexinidazole Winthrop, a Sanofi-Aventis product developed with the DNDi, received a positive endorsement from the European Medicines Agency on November 15th, 2018, for use in non-European markets.[10][11] It was approved for the treatment of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) in December 2018.[12]

See alsoEdit

ReferencesEdit

  1. ^ a b Raether, W; Seidenath, H (1983). "The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica". Annals of Tropical Medicine and Parasitology. 77 (1): 13–26. PMID 6411009.
  2. ^ Jennings, FW; Urquhart, GM (1983). "The use of the 2 substituted 5-nitroimidazole, Fexinidazole (Hoe 239) in the treatment of chronic T. brucei infections in mice". Zeitschrift für Parasitenkunde. 69 (5): 577–581. doi:10.1007/bf00926669. PMID 6636983.
  3. ^ a b Wyllie, S; Patterson, S; Stojanovski, L; Simeons, FRC; Norval, S; Kime, R; Read, RD; Fairlamb, AH (2012). "The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis". Science Translational Medicine. 4 (119): 119re1. doi:10.1126/scitranslmed.3003326. PMC 3457684. PMID 22301556.
  4. ^ Sokolova, AY; Wyllie, S; Patterson, S; Oza, SL; Read, RD; Fairlamb, AH (2010). "Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis". Antimicrobial Agents and Chemotherapy. 54 (7): 2893–900. doi:10.1128/AAC.00332-10. PMC 2897277. PMID 20439607.
  5. ^ "Jump-Start on Slow Trek to Treatment for a Disease". New York Times. January 8, 2008.
  6. ^ "Fexinidazole Progresses into Clinical Development". DNDi Newsletter. November 2009.
  7. ^ "Sanofi-aventis and DNDi enter into a Collaboration Agreement on a New Drug for Sleeping Sickness, Fexinidazole". DNDi. May 18, 2009.
  8. ^ Torreele, E; Bourdin Trunz, B; Tweats, D; Kaiser, M; Brun, R; Mazué, G; Bray, MA; Pécoul, B (2010). Boelaert, Marleen (ed.). "Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness". PLOS Neglected Tropical Diseases. 4 (12): e923. doi:10.1371/journal.pntd.0000923. PMC 3006138. PMID 21200426.
  9. ^ DNDi (4 November 2017). "Phase II/III studies show high efficacy and safety of fexinidazole, the first oral treatment for sleeping sickness". dndi.org. Retrieved 20 November 2018.
  10. ^ "CHMP Summary of Opinion - Fexinidazole Winthrop" (PDF). Retrieved 19 November 2018.
  11. ^ Donald G. McNeil, Jr. (16 November 2018). "Rapid Cure Approved for Sleeping Sickness, a Horrific Illness". nytimes.com. Retrieved 20 November 2018.
  12. ^ "Fexinidazole, the first all-oral treatment for sleeping sickness, approved in Democratic Republic of Congo | DNDi". Drugs for Neglected Diseases initiative (DNDi). Retrieved 2019-06-04.