Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Perspective

Oteseconazole: First Approved Orally Bioavailable and Selective CYP51 Inhibitor for the Treatment of Patients with Recurrent Vulvovaginal Candidiasis

Author(s): Surya K. De*

Volume 30, Issue 37, 2023

Published on: 03 March, 2023

Page: [4170 - 4175] Pages: 6

DOI: 10.2174/0929867330666230220130024

Open Access Journals Promotions 2
conference banner
Abstract

Oteseconazole was approved by the US FDA in April 2022. It is the first approved selective and orally bioavailable CYP51 inhibitor for the treatment of patients with recurrent Vulvovaginal candidiasis. Herein, we describe its dosage, administration, chemical structure, physical properties, synthesis, mechanism of action, and pharmacokinetics.

Keywords: Antifungals, mechanism of action, fungal lanosterol demethylase, vaginitis, sterol biosynthesis, oteseconazole.

[1]
Sobel, J.D. Vulvovaginal candidosis. Lancet, 2007, 369(9577), 1961-1971.
[http://dx.doi.org/10.1016/S0140-6736(07)60917-9] [PMID: 17560449]
[2]
Zhang, J.; Li, L.; Lv, Q.; Yan, L.; Wang, Y.; Jiang, Y. The fungal CYP51s: Their functions, structures, related drug resistance, and inhibitors. Front. Microbiol., 2019, 10, 691.
[http://dx.doi.org/10.3389/fmicb.2019.00691] [PMID: 31068906]
[3]
Chang, Y.L.; Yu, S.J.; Heitman, J.; Wellington, M.; Chen, Y.L. New facets of antifungal therapy. Virulence, 2017, 8(2), 222-236.
[http://dx.doi.org/10.1080/21505594.2016.1257457] [PMID: 27820668]
[4]
Hargrove, T.Y.; Friggeri, L.; Wawrzak, Z.; Qi, A.; Hoekstra, W.J.; Schotzinger, R.J.; York, J.D.; Guengerich, F.P.; Lepesheva, G.I. Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis. J. Biol. Chem., 2017, 292(16), 6728-6743.
[http://dx.doi.org/10.1074/jbc.M117.778308] [PMID: 28258218]
[5]
Brand, S.R.; Sobel, J.D.; Nyirjesy, P.; Ghannoum, M.A.; Schotzinger, R.J.; Degenhardt, T.P. A randomized phase 2 study of VT-1161 for the treatment of acute vulvovaginal candidiasis. Clin. Infect. Dis., 2021, 73(7), e1518-e1524.
[http://dx.doi.org/10.1093/cid/ciaa1204] [PMID: 32818963]
[6]
Seiler, G.T.; Ostrosky-Zeichner, L. Investigational agents for the treatment of resistant yeasts and molds. Curr. Fungal Infect. Rep., 2021, 15(3), 104-115.
[http://dx.doi.org/10.1007/s12281-021-00419-5] [PMID: 34075318]
[7]
Stewart, A.G.; Paterson, D.L. How urgent is the need for new antifungals? Expert Opin. Pharmacother., 2021, 22(14), 1857-1870.
[http://dx.doi.org/10.1080/14656566.2021.1935868] [PMID: 34231434]
[8]
Sobel, J.D.; Nyirjesy, P. Oteseconazole: An advance in treatment of recurrent vulvovaginal candidiasis. Future Microbiol., 2021, 16(18), 1453-1461.
[http://dx.doi.org/10.2217/fmb-2021-0173] [PMID: 34783586]
[9]
Gupta, A.K.; Talukder, M.; Venkataraman, M. Review of the alternative therapies for onychomycosis and superficial fungal infections: Posaconazole, fosravuconazole, voriconazole, oteseconazole. Int. J. Dermatol., 2021, 61(12), 1431-1441.
[http://dx.doi.org/10.1111/ijd.15999] [PMID: 34882787]
[10]
Tortorano, A.M.; Prigitano, A.; Morroni, G.; Brescini, L.; Barchiesi, F. Candidemia: Evolution of drug resistance and novel therapeutic approaches. Infect. Drug Resist., 2021, 14, 5543-5553.
[http://dx.doi.org/10.2147/IDR.S274872] [PMID: 34984009]
[11]
Nyirjesy, P.; Brookhart, C.; Lazenby, G.; Schwebke, J.; Sobel, J.D. Vulvovaginal candidiasis: A review of the evidence for the 2021 centers for disease control and prevention of sexually transmitted infections treatment guidelines. Clin. Infect. Dis., 2022, 74(Suppl. 2), S162-S168.
[http://dx.doi.org/10.1093/cid/ciab1057] [PMID: 35416967]
[12]
Hoenigl, M.; Sprute, R.; Arastehfar, A.; Perfect, J.R.; Lass-Flörl, C.; Bellmann, R.; Prattes, J.; Thompson, G.R., III; Wiederhold, N.P.; Al Obaidi, M.M.; Willinger, B.; Arendrup, M.C.; Koehler, P.; Oliverio, M.; Egger, M.; Schwartz, I.S.; Cornely, O.A.; Pappas, P.G.; Krause, R. Invasive candidiasis: Investigational drugs in the clinical development pipeline and mechanisms of action. Expert Opin. Investig. Drugs, 2022, 31(8), 795-812.
[http://dx.doi.org/10.1080/13543784.2022.2086120] [PMID: 35657026]
[13]
Logan, A.; Wolfe, A.; Williamson, J.C. Antifungal resistance and the role of new therapeutic agents. Curr. Infect. Dis. Rep., 2022, 24(9), 105-116.
[http://dx.doi.org/10.1007/s11908-022-00782-5] [PMID: 35812838]
[14]
Martens, M.G.; Maximos, B.; Degenhardt, T.; Person, K.; Curelop, S.; Ghannoum, M.; Flynt, A.; Brand, S.R. Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections. Am. J. Obstet. Gynecol., 2022, 227(6), 880.e1-880.e11.
[http://dx.doi.org/10.1016/j.ajog.2022.07.023] [PMID: 35863457]
[15]
Wiederhold, N.P. Pharmacodynamics, mechanisms of action and resistance, and spectrum of activity of new antifungal agents. J. Fungi, 2022, 8(8), 857.
[http://dx.doi.org/10.3390/jof8080857] [PMID: 36012845]
[16]
Hoekstra, W.J.; Garvey, E.P.; Moore, W.R.; Rafferty, S.W.; Yates, C.M.; Schotzinger, R.J. Design and optimization of highly-selective fungal CYP51 inhibitors. Bioorg. Med. Chem. Lett., 2014, 24(15), 3455-3458.
[http://dx.doi.org/10.1016/j.bmcl.2014.05.068] [PMID: 24948565]
[17]
Hoekstra, W.J.; Yates, C.M. Mycovia Pharmaceuticals Inc, Antifungal compound process. US10836740B2, 2020.
[18]
Warrilow, A.G.S.; Parker, J.E.; Price, C.L.; Nes, W.D.; Garvey, E.P.; Hoekstra, W.J.; Schotzinger, R.J.; Kelly, D.E.; Kelly, S.L. The investigational drug VT-1129 is a highly potent inhibitor of cryptococcus species CYP51 but only weakly inhibits the human enzyme. Antimicrob. Agents Chemother., 2016, 60(8), 4530-4538.
[http://dx.doi.org/10.1128/AAC.00349-16] [PMID: 27161631]
[19]
Murphy, S.E.; Bicanic, T. Drug resistance and novel therapeutic approaches in invasive candidiasis. Front. Cell. Infect. Microbiol., 2021, 11, 759408.
[http://dx.doi.org/10.3389/fcimb.2021.759408] [PMID: 34970504]
[20]
Vanreppelen, G.; Nysten, J.; Baldewijns, S.; Sillen, M.; Donders, G.; Van Dijck, P. Oteseconazole (VIVOJA) for prevention of recurrent vulvovaginal candidiasis. Trends Pharmacol. Sci., 2023, 44(1), 64-65.
[http://dx.doi.org/10.1016/j.tips.2022.10.004] [PMID: 36396498]
[21]
Nishimoto, A.T.; Whaley, S.G.; Wiederhold, N.P.; Zhang, Q.; Yates, C.M.; Hoekstra, W.J.; Schotzinger, R.J.; Garvey, E.P.; Rogers, P.D. Impact of the major candida glabrata triazole resistance determinants on the activity of the novel investigational tetrazoles VT-1598 and VT-1161. Antimicrob. Agents Chemother., 2019, 63(10), e01304-e01319.
[http://dx.doi.org/10.1128/AAC.01304-19] [PMID: 31383660]
[22]
Break, T.J.; Desai, J.V.; Natarajan, M.; Ferre, E.M.N.; Henderson, C.; Zelazny, A.M.; Siebenlist, U.; Hoekstra, W.J.; Schotzinger, R.J.; Garvey, E.P.; Lionakis, M.S. VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole-susceptible and -resistant Candida albicans. J. Antimicrob. Chemother., 2018, 73(1), 151-155.
[http://dx.doi.org/10.1093/jac/dkx352] [PMID: 29040636]

© 2024 Bentham Science Publishers | Privacy Policy