Orotomides are a class of experimental

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryp ...

s. They were discovered in 2015 by British scientists at the pharmaceutical company F2G Ltd. while searching for a new drug for ''

Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Mich ...

'' infection. The discovery was formally announced at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 55th meeting during 17-21 September 2015 at San Diego, California, and published the next year in the ''

Proceedings of the National Academy of Sciences ''Proceedings of the National Academy of Sciences of the United States of America'' (often abbreviated ''PNAS'' or ''PNAS USA'') is a peer-reviewed multidisciplinary scientific journal. It is the official journal of the National Academy of Scien ...

''. It was found to be effective against most important human fungal infections including those with ''Aspergillus'', ''Lemontospora (Scedosporium) prolificans'', ''Fusarium'', ''Penicillium'' spp., and ''Taloromyces''. The most promising drug candidate is designated F901318, chemical name 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N--2-oxo-acetamide. F901318 has been named Olorofim. Unlike other antifungal drugs, the orotomides act differently by stopping

pyrimidine biosynthesis Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...

in fungal cells. They cause reversible inhibition of

dihydroorotate dehydrogenase Dihydroorotate dehydrogenase (DHODH) is an enzyme that in humans is encoded by the ''DHODH'' gene on chromosome 16. The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to ...

(DHODH), an enzyme that catalyses dihydroorotate to

orotate Orotic acid is a pyrimidinedione and a carboxylic acid. Historically, it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin. The compound is synthesized in the body via a m ...

. This inhibition in turn block the growth of hyphae. This unique action makes it more effective than other antifungal drugs. Originally named the F3 series, the name was changed to orotomides, combining the names of the compound (dihydroorotate) they acted upon with the chemical group (α-ketoamide) which they belong to. The

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) Committee for Orphan Medicinal Products granted orphan designation to F2G for F901318 for the treatment of scedosporiosis on 29 August 2016, and for invasive

aspergillosis Aspergillosis is a fungal infection of usually the lungs, caused by the genus ''Aspergillus'', a common mould that is breathed in frequently from the air around, but does not usually affect most people. It generally occurs in people with lung dise ...

on 14 October 2016. As of May 2017, F901318 is in late phase 1 clinical trials. It was shown to be useful for acute sinopulmonary aspergillosis caused by ''

Aspergillus flavus ''Aspergillus flavus'' is a saprotrophic and pathogenic fungus with a cosmopolitan distribution. It is best known for its colonization of cereal grains, legumes, and tree nuts. Postharvest rot typically develops during harvest, storage, and/or ...

''.

References

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