Chemistry:Ibrexafungerp

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Ibrexafungerp, sold under the brand name Brexafemme, is an antifungal medication used to treat vulvovaginal candidiasis (VVC) (vaginal yeast infection).[1] It is taken orally (by mouth).[1] It is also currently undergoing clinical trials for other indications via an intravenous (IV) formulation. An estimated 75% of women will have at least one episode of VVC and 40 to 45% will have two or more episodes in their lifetime.[2]

Ibrexafungerp acts via inhibition of glucan synthase, which prevents formation of the fungal cell wall.[1]

Ibrexafungerp was approved for medical use in the United States in June 2021.[1][3] It is the first non-azole oral antifungal drug to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of vaginal yeast infections.[3] The FDA considers it to be a first-in-class medication.[4]

Medical uses

Ibrexafungerp is indicated for the treatment of adult and postmenarchal pediatric females with vulvovaginal candidiasis (VVC).[1][3]

Ibrexafungerp is currently undergoing late-stage clinical trials for an intravenous formulation for the treatment of various fungal diseases, including life-threatening fungal infections caused primarily by Candida (including C. auris) and Aspergillus species. It has demonstrated broad-spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains.[5]

Pharmacology

Pharmacodynamics

Ibrexafungerp is a triterpenoid antifungal agent.[1] It acts via inhibition of the enzyme glucan synthase, which is involved in the formation of 1,3-β-D-glucan—an essential component of the fungal cell wall.[1] The compound has concentration-dependent fungicidal activity against Candida species.[1]

Pharmacokinetics

Ibrexafungerp has a time to maximal concentrations of 4 to 6 hours.[1] It is metabolized by hydroxylation via CYP3A4 and subsequently by glucuronidation and sulfation.[1] The medication has an elimination half-life of approximately 20 hours.[1]

Synthesis

Synthetic pathway of ibrexafungerp, adapted from Scheme 1 of McInturff et al. 2023.[6]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Cite error: Invalid <ref> tag; no text was provided for refs named Brexafemme FDA label
  2. ↑ "Vulvovaginal Candidiasis - STI Treatment Guidelines" (in en-us). U.S. Centers for Disease Control and Prevention. 22 July 2021. https://www.cdc.gov/std/treatment-guidelines/candidiasis.htm. 
  3. ↑ 3.0 3.1 3.2 "Scynexis Announces FDA Approval of Brexafemme (ibrexafungerp tablets) as the First and Only Oral Non-Azole Treatment for Vaginal Yeast Infections". Scynexis, Inc. (Press release). 2 June 2021. Archived from the original on 31 December 2021. Retrieved 2 June 2021.
  4. ↑ (PDF) Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (Report). 13 May 2022. https://www.fda.gov/media/155227/download. Retrieved 22 January 2023.  Public Domain This article incorporates text from this source, which is in the public domain.
  5. ↑ "SCYNEXIS Announces Successful Completion of Phase 1 Trial Evaluating Intravenous (IV) Formulation of Ibrexafungerp". Scynexis inc.. 9 November 2021. https://www.scynexis.com/news-media/press-releases/detail/260/scynexis-announces-successful-completion-of-phase-1-trial. 
  6. ↑ "Synthetic Approaches to the New Drugs Approved During 2021". Journal of Medicinal Chemistry (American Chemical Society (ACS)) 66 (15): 10150–10201. August 2023. doi:10.1021/acs.jmedchem.3c00501. PMID 37528515. 

Further reading



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