Ibrexafungerp

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;
Routes of; administration	oral, intravenous
Drug class	Antifungal
ATC code	J02AX07 (WHO) ;
Legal status
Legal status	US: WARNINGRx-only;
Pharmacokinetic data
Protein binding	>99%
Metabolism	Hydroxylation (CYP3A4) then conjugation (glucuronidation, sulfation)
Elimination half-life	20 hours
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, 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.^[3]

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]^[4] 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.^[4] The FDA considers it to be a first-in-class medication.^[5]

Medical uses

Ibrexafungerp is indicated for the treatment of adult and postmenarchal pediatric females with vulvovaginal candidiasis (VVC).^[1]^[4]

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.^[6]

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.^[7]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p "Brexafemme- ibrexafungerp tablet, film coated". DailyMed. U.S. National Library of Medicine. Retrieved 12 September 2021.
^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
^ "Vulvovaginal Candidiasis - STI Treatment Guidelines". U.S. Centers for Disease Control and Prevention. 22 July 2021. Retrieved 6 April 2022.
^ ^a ^b ^c "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.
^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. This article incorporates text from this source, which is in the public domain.
^ "SCYNEXIS Announces Successful Completion of Phase 1 Trial Evaluating Intravenous (IV) Formulation of Ibrexafungerp". www.scynexis.com. Scynexis inc. 9 November 2021. Archived from the original on 20 October 2022. Retrieved 20 October 2022.
^ McInturff EL, France SP, Leverett CA, Flick AC, Lindsey EA, Berritt S, et al. (August 2023). "Synthetic Approaches to the New Drugs Approved During 2021". Journal of Medicinal Chemistry. 66 (15). American Chemical Society (ACS): 10150–10201. doi:10.1021/acs.jmedchem.3c00501. PMID 37528515. S2CID 260377572.

External links

"Ibrexafungerp". Drug Information Portal. U.S. National Library of Medicine.
Clinical trial number NCT03734991 for "Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs. Placebo in Subjects With Acute Vulvovaginal Candidiasis (VANISH 303)" at ClinicalTrials.gov
Clinical trial number NCT03987620 for "Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs. Placebo in Subjects With Acute Vulvovaginal Candidiasis (Vanish 306)" at ClinicalTrials.gov

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[Brexafemme_FDA_label-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p "Brexafemme- ibrexafungerp tablet, film coated". DailyMed. U.S. National Library of Medicine. Retrieved 12 September 2021.

[FDA-AllBoxedWarnings-2] "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.

[3] "Vulvovaginal Candidiasis - STI Treatment Guidelines". U.S. Centers for Disease Control and Prevention. 22 July 2021. Retrieved 6 April 2022.

[Scynexis_PR-4] "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.

[New_Drug_Therapy_Approvals_2021-5] Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. This article incorporates text from this source, which is in the public domain.

[6] "SCYNEXIS Announces Successful Completion of Phase 1 Trial Evaluating Intravenous (IV) Formulation of Ibrexafungerp". www.scynexis.com. Scynexis inc. 9 November 2021. Archived from the original on 20 October 2022. Retrieved 20 October 2022.

[McInturff_France_Leverett_Flick_2023_pp._10150–10201-7] McInturff EL, France SP, Leverett CA, Flick AC, Lindsey EA, Berritt S, et al. (August 2023). "Synthetic Approaches to the New Drugs Approved During 2021". Journal of Medicinal Chemistry. 66 (15). American Chemical Society (ACS): 10150–10201. doi:10.1021/acs.jmedchem.3c00501. PMID 37528515. S2CID 260377572.

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