Fosravuconazole

Last updated
Fosravuconazole
Fosravuconazole.svg
Clinical data
Trade names Nailin
Other namesBMS-379224; BFE-1224; E-1224
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
  • [(2R,3R)-3-[4-(4-Cyanophenyl)-1,3-thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-yl]oxymethyl dihydrogen phosphate
CAS Number
PubChem CID
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C23H20F2N5O5PS
Molar mass 547.47 g·mol−1
3D model (JSmol)
  • C[C@@H](c1nc(-c2ccc(C#N)cc2)cs1)[C@@](Cn1cncn1)(OCOP(=O)(O)O)c1ccc(F)cc1F
  • InChI=1S/C23H20F2N5O5PS/c1-15(22-29-21(10-37-22)17-4-2-16(9-26)3-5-17)23(11-30-13-27-12-28-30,34-14-35-36(31,32)33)19-7-6-18(24)8-20(19)25/h2-8,10,12-13,15H,11,14H2,1H3,(H2,31,32,33)/t15-,23+/m0/s1
  • Key:SYTNEMZCCLUTNX-NPMXOYFQSA-N

Fosravuconazole (trade name Nailin) is a triazole antifungal agent. [1] [2] In Japan, it is approved for the treatment of onychomycosis, a fungal infection of the nail. [3] It is a prodrug that is converted into ravuconazole. [1]

Drugs for Neglected Diseases Initiative (DNDi) and the Japanese pharmaceutical company Eisai found that fosravuconazole works as a treatment for mycetoma, a serious condition. [1] [4] [5] The Phase II clinical trial found that oral fosravuconazole was safe, patient-friendly, and effective in treating eumycetoma. [6] [7] Eumycetoma mainly affects young adults in poorer, rural areas; the standard treatment is itraconazole, which is much more expensive at about US$2,000 for a year than fosravuconazole and unaffordable, and not available in all endemic countries. [7]

Related Research Articles

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A nail disease or onychosis is a disease or deformity of the nail. Although the nail is a structure produced by the skin and is a skin appendage, nail diseases have a distinct classification as they have their own signs and symptoms which may relate to other medical conditions. Some nail conditions that show signs of infection or inflammation may require medical assistance.

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

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 cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

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<span class="mw-page-title-main">Eisai (company)</span> Japanese pharmaceutical company

Eisai Co., Ltd. is a Japanese pharmaceutical company headquartered in Tokyo, Japan. It has some 10,000 employees, among them about 1,500 in research. Eisai is listed on the Tokyo Stock Exchange and is a member of the Topix 100 and Nikkei 225 stock indices.

<span class="mw-page-title-main">Onychomycosis</span> Medical condition

Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Toenails or fingernails may be affected, but it is more common for toenails. Complications may include cellulitis of the lower leg. A number of different types of fungus can cause onychomycosis, including dermatophytes and Fusarium. Risk factors include athlete's foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, and poor immune function. The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing.

<span class="mw-page-title-main">Zonisamide</span> Chemical compound

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Basilea Pharmaceutica is a multinational specialty biopharmaceutical company headquartered in Basel, Switzerland. It was formed as a spin-off entity from the drug giant Hoffmann–La Roche in October 2000. It is engaged in the development of antibiotics, antifungals and oncology drugs for treatment of invasive aspergillosis and mucormycosis. Basilea is publicly traded on the SIX Swiss exchange.

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<span class="mw-page-title-main">Ravuconazole</span> Chemical compound

Ravuconazole is a potent triazole antifungal, the development of which was discontinued in 2007. The drug has shown to have a similar spectrum of activity to voriconazole, with an increased half-life. However, ravuconazole has limited activity against species of Fusarium, Scedosporium, and Zygomycetes.

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<span class="mw-page-title-main">Varespladib</span> Chemical compound

Varespladib is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2). The molecule acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation. From 2006 to 2012, varespladib was under active investigation by Anthera Pharmaceuticals as a potential therapy for several inflammatory diseases, including acute coronary syndrome and acute chest syndrome. The trial was halted in March 2012 due to inadequate efficacy. The selective sPLA2 inhibitor varespladib (IC50 value 0.009 μM in chromogenic assay, mole fraction 7.3X10-6) was studied in the VISTA-16 randomized clinical trial (clinicaltrials.gov Identifier: NCT01130246) and the results were published in 2014. The sPLA2 inhibition by varespladib in this setting seemed to be potentially harmful, and thus not a useful strategy for reducing adverse cardiovascular outcomes from acute coronary syndrome. Since 2016, scientific research has focused on the use of Varespladib as an inhibitor of snake venom toxins using various types of in vitro and in vivo models. Varespladib showed a significant inhibitory effect to snake venom PLA2 which makes it a potential first-line drug candidate in snakebite envenomation therapy. In 2019, the U.S. Food and Drug Administration (FDA) granted varespladib orphan drug status for its potential to treat snakebite.

<span class="mw-page-title-main">Favipiravir</span> Experimental antiviral drug with potential activity against RNA viruses

Favipiravir, sold under the brand name Avigan among others, is an antiviral medication used to treat influenza in Japan. It is also being studied to treat a number of other viral infections, including SARS-CoV-2. Like the experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.

<span class="mw-page-title-main">Efinaconazole</span> Chemical compound

Efinaconazole, sold under the brand name Jublia among others, is a triazole antifungal medication. It is approved for use in the United States, Canada, and Japan as a 10% topical solution for the treatment of onychomycosis. Efinaconazole acts as a 14α-demethylase inhibitor.

<span class="mw-page-title-main">Tavaborole</span> Chemical compound

Tavaborole, sold under the brand name Kerydin, is a topical antifungal medication for the treatment of onychomycosis, a fungal infection of the nail and nail bed with a complete clearance rate of 6-7% and partial clearance rate of 23-24% in individuals whose “infection border does not reach the cuticle at the base of the large toenail.” Tavaborole was approved by the US FDA in July 2014. The medication inhibits an essential fungal enzyme, leucyl-tRNA synthetase, that is required for protein synthesis. The inhibition of protein synthesis leads to termination of cell growth and then cell death, eliminating the fungal infection.

The Global Health Innovative Technology Fund, headquartered in Japan, is an international public-private partnership between the Government of Japan, 16 pharmaceutical and diagnostics companies, the Bill & Melinda Gates Foundation, the Wellcome Trust and United Nations Development Programme. It funds scientific research and development for anti-infectives and diagnostics for diseases that primarily affect the developing world. Bill Gates has noted that "GHIT draws on the immense innovation capacity of Japan’s pharmaceutical companies, universities and research institutions to accelerate the creation of new vaccines, drugs and diagnostic tools for global health." Margaret Chan, former Director-General of the World Health Organization, said: "The GHIT Fund has stepped in to provide that incentive in a pioneering model of partnership that brings Japanese innovation, investment and leadership to the global fight against infectious disease."

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Baloxavir marboxil, sold under the brand name Xofluza, is an antiviral medication for treatment of influenza A and influenza B. It was approved for medical use both in Japan and in the United States in 2018, and is taken as a single dose by mouth. It may reduce the duration of flu symptoms by about a day, but is prone to selection of resistant mutants that render it ineffectual.

<span class="mw-page-title-main">Oteseconazole</span> Chemical compound

Oteseconazole, a novel orally bioavailable and selective inhibitor of fungal cytochrome P450 enzyme 51 (CYP51), has shown promising efficacy in the treatment of recurrent vulvovaginal candidiasis (RVVC) in patients.

References

  1. 1 2 3 Yamaguchi H (2016). "Potential of Ravuconazole and its Prodrugs as the New OralTherapeutics for Onychomycosis". Medical Mycology Journal. 57 (4): E93–E110. doi:10.3314/mmj.16-00006. PMID   27904057.
  2. "Fosravuconazole - Seren Pharmaceuticals". Adis Insight. Springer Nature Switzerland AG.
  3. "Oral Antifungal Agent Nailin Capsules 100 mg Approved in Japan" (Press release). Eisai. January 19, 2018.
  4. "Fosravuconazole". Drugs for Neglected Diseases Initiative. 23 November 2023 [Project started in 2015; updated in 2023 with results of the Phase II clinical trial].
  5. "Drugs for Neglected Diseases initiative and Eisai Co., Ltd. to Test Drug Candidate for Eumycetoma" (Press release). Eisai Co., Ltd. 10 September 2015.
  6. "World's first clinical trial for devastating fungal disease mycetoma shows efficacy of new, promising treatment" (Press release). Drugs for Neglected Diseases initiative (DNDi). 23 November 2023.
  7. 1 2 Johnson, Sarah (23 November 2023). "Cheap over-the-counter nail drug found to work on crippling flesh-eating disease". The Guardian. The head of mycetoma at the DNDi labelled the discovery 'momentous', and said 'We were all very excited, it's going to be a gamechanger'.