NDLI: Review of the novel antifungal drug olorofim (F901318)

Content Provider	Springer Nature : BioMed Central
Author	Vanbiervliet, Yuri Van Nieuwenhuyse, Tine Aerts, Robina Lagrou, Katrien Spriet, Isabel Maertens, Johan
Abstract	There is clearly a need for novel antifungal agents, not only concerning spectrum, but also oral bioavailability, tolerability, and drug-drug interactions. There is growing concern for antifungal resistance for current available antifungals, mainly driven by environmental fungicide use or long-term exposure to antifungals, in the setting of mould-active prophylaxis or for chronic antifungal infections, such as chronic pulmonary aspergillosis. Moreover, the incidence of breakthrough infections is increasing, because of the introduction of (mould-active) prophylaxis (1-4). There is emergence of difficult to treat invasive fungal infections, such as those caused by Lomentospora prolificans, cryptic species of Aspergillus, Scedosporium and Coccidioides. Olorofim (F901318) is the first-in class of the orotomides, a novel antifungal class targeting dihydroorotate dehydrogenase (DHODH), a key enzyme in the biosynthesis of pyrimidines. Olorofim shows good in vitro and in vivo activity against Aspergillus species, rare and difficult to treat moulds and endemic dimorphic fungi, including azole- and amphotericin-resistant isolates. It lacks activity against yeasts and the Mucorales species. It is only orally available and shows very promising results in ongoing clinical trials. In this review we will describe the mechanism of action of olorofim, the spectrum of activity in vitro and in vivo, pharmacokinetics, pharmacodynamics, drug-drug interactions, resistance, and clinical outcomes.
Related Links	https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-024-10143-3.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14712334
DOI	10.1186/s12879-024-10143-3
Journal	BMC Infectious Diseases
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-07
Access Restriction	Open
Subject Keyword	Infectious Diseases Parasitology Medical Microbiology Tropical Medicine Internal Medicine Novel antifungal therapy Dihydroorotate dehydrogenase Olorofim F901318 Invasive fungal diseases Aspergillus Lomentospora Scedosporium Coccidioides
Content Type	Text
Resource Type	Review
Subject	Infectious Diseases
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.3/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Correction: Review of the novel antifungal drug olorofim (F901318)

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In Vitro Activity of the Novel Antifungal Olorofim against Scedosporium and Lomentospora prolificans.

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Correction: Review of the novel antifungal drug olorofim (F901318)

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