Ibrexafungerp

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

Clinical data
Pronunciation	/aɪˌbrɛksəˈfʌndʒɜːrp/ eye-BREKS-ə-FUN-jurp
Trade names	Brexafemme
Other names	SCY-078
License data	US DailyMed: Ibrexafungerp
Pregnancy category	Contraindicated[1]
Routes of administration	oral, intravenous
Drug class	Antifungal
ATC code	J02AX07 (WHO)
Legal status
Legal status	US: ℞-only[1]
Pharmacokinetic data
Protein binding	>99%[1]
Metabolism	Hydroxylation (CYP3A4) then conjugation (glucuronidation, sulfation)[1]
Elimination half-life	20 hours[1]
Identifiers
IUPAC name (1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-21-[(2R)-2-amino-2,3,3-trimethylbutoxy]-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-20-(5-pyridin-4-yl-1,2,4-triazol-1-yl)-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-ene-6-carboxylic acid
CAS Number	1207753-03-4 as citrate: 1965291-08-0
PubChem CID	46871657 as citrate: 137552087
DrugBank	DB12471 as citrate: DBSALT003185
UNII	A92JFM5XNU as citrate: M4NU2SDX3E
KEGG	D11544 as citrate: D11545
ChEMBL	ChEMBL4297513 as citrate: ChEMBL4298168
CompTox Dashboard (EPA)	DTXSID901336871
Chemical and physical data
Formula	C44H67N5O4
Molar mass	730.051 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)[C@@H](C)[C@@]1(C)CC[C@]2(C)[C@H]3CC[C@H]4[C@@]5(C)COC[C@@]4(C[C@@H](n4ncnc4-c4ccncc4)[C@@H]5OC[C@](C)(N)C(C)(C)C)C3=CC[C@@]2(C)[C@@H]1C(=O)O
InChI InChI=1S/C44H67N5O4/c1-27(2)28(3)39(7)18-19-41(9)30-12-13-33-40(8)23-52-25-44(33,31(30)14-17-42(41,10)34(39)37(50)51)22-32(35(40)53-24-43(11,45)38(4,5)6)49-36(47-26-48-49)29-15-20-46-21-16-29/h14-16,20-21,26-28,30,32-35H,12-13,17-19,22-25,45H2,1-11H3,(H,50,51)/t28-,30+,32-,33+,34-,35+,39-,40-,41-,42+,43+,44+/m1/s1 Key:BODYFEUFKHPRCK-ZCZMVWJSSA-N

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]