Details of the Drug Combination

General Information of Drug Combination (ID: DC84E2P)

• Drug Combination Name: Ibrexafungerp + Fluconazole
• Indication: Recurrent Vulvovaginal Candidiasis; Status: Phase 3 [1]
• Component Drugs:
  Ibrexafungerp (DMK1IPV): Small molecular drug
  Fluconazole (DMOWZ6B): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ibrexafungerp

Disease Entry	ICD 11	Status	REF
Vulvovaginal Candidiasis	1F23.10	Approved	[2]
Invasive candidiasis	1F23	Phase 3	[3]
Fungal infection	1F29-1F2F	Phase 2	[4]

Ibrexafungerp Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fungal 1,3-beta-glucan synthase (Fung GSC2)	TT0SFXH	FKS2_YEAST	Inhibitor	[7]

Indication(s) of Fluconazole

Disease Entry	ICD 11	Status	REF
Cryptococcal meningitis	N.A.	Approved	[5]
Fungal infection	1F29-1F2F	Approved	[6]
Invasive candidiasis	1F23	Approved	[5]
Mycoses	1F2Z	Approved	[5]
Oral candidiasis	1F23.0	Approved	[5]
Autoimmune polyendocrine syndrome type 1	N.A.	Investigative	[5]
Candidemia	1F23.3Y	Investigative	[5]
Esophageal candidiasis	N.A.	Investigative	[5]

Fluconazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Cytochrome P450 51 (Candi ERG11)	TTTSOUD	CP51_CANAL	Modulator	[9]

Fluconazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]

Fluconazole Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[11]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[12]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Affects Activity	[13]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[13]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Increases Expression	[14]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Response To Substance	[15]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases ADR	[8]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Metabolism	[16]

References

• [1] ClinicalTrials.gov (NCT04029116) Phase 3 Study of Oral Ibrexafungerp (SCY-078) Vs. Placebo in Subjects With Recurrent Vulvovaginal Candidiasis (VVC)
• [2] FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 214900.
• [3] ClinicalTrials.gov (NCT03059992) Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment (FURI). U.S. National Institutes of Health.
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031918)
• [5] Fluconazole FDA Label
• [6] Fluconazole use as an important risk factor in the emergence of fluconazole-resistant Candida glabrata fungemia. Arch Intern Med. 2009 Aug 10;169(15):1444-5; author reply 1445.
• [7] Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model. Antimicrob Agents Chemother. 2015 Feb;59(2):1265-72.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Effect of fluconazole on plasma fluvastatin and pravastatin concentrations. Eur J Clin Pharmacol. 2000 Jun;56(3):225-9.
• [11] The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
• [12] CYP3A4 substrate selection and substitution in the prediction of potential drug-drug interactions. J Pharmacol Exp Ther. 2005 Jul;314(1):180-90.
• [13] The classic azole antifungal drugs are highly potent endocrine disruptors in vitro inhibiting steroidogenic CYP enzymes at concentrations lower than therapeutic Cmax. Toxicology. 2019 Sep 1;425:152247. doi: 10.1016/j.tox.2019.152247. Epub 2019 Jul 19.
• [14] Fluconazole inhibits human adrenocortical steroidogenesis in vitro. J Endocrinol. 2012 Dec;215(3):403-12. doi: 10.1530/JOE-12-0310. Epub 2012 Oct 4.
• [15] Differential azole antifungal efficacies contrasted using a Saccharomyces cerevisiae strain humanized for sterol 14 alpha-demethylase at the homolo... Antimicrob Agents Chemother. 2008 Oct;52(10):3597-603.
• [16] [Simultaneous determination of the inhibitory potency of compounds on the activity of five cytochrome P-450 enzymes using a cocktail probe substrates method]. Yao Xue Xue Bao. 2007 Jun;42(6):589-94.