Advances in Antifungal Drug Development: An Up-To-Date Mini Review
Abstract
:1. Introduction
2. Clinically Used Antifungals
3. Novel Antifungals (In Clinical Settings)
3.1. Aryldiamidines—T-2307
3.2. Fosmanogepix and Manogepix
3.3. Nikkomycin Z
3.4. Orotomides—Olorofim
3.5. Cyclic Peptides—VL-2397
3.6. Cyclic Peptides—Aureobasidin A
3.7. MGCD290
3.8. Tetrazoles
3.9. Triterpenoids—Ibrexafungerp
3.10. Triazoles
3.11. BSG005
3.12. Cyclic Peptides—Rezafungin
3.13. SUBA Itraconazole
3.14. Topical Terbinafine Solution
3.15. Amphotericin B Cochleate
3.16. Metal Complexes and Chelates
4. New Compounds as Potential Antifungals (In Preclinical Stages)
5. Repurposing
6. Immunotherapy
7. New Promising Targets for Antifungal Development
8. Conclusions and Remarks
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Agent | Spectrum of Activity | Route of Administration | Company/Sponsor | Current Status | Clinical Trial Registration Number |
---|---|---|---|---|---|
T-2307 | Broad spectrum | IV | Toyama Chemical Ltd. | Phase I completed (as stated in [57], but no actual data available in the literature) | Not available |
Fosmanogepix | Candida spp. (except C. krusei) and Aspergillus spp. | PO/IV | Amplyx Pharmaceuticals | Phase II recruiting | NCT04240886 |
Nikkomycin Z | Candida spp. and Aspergillus spp. | PO | University of Arizona | Phase I completed; however lack of funding and volunteers caused the termination of phase II studies | NCT00834184 |
Olorofim | Aspergillus spp. and uncommon molds | PO/IV | F2G Ltd. | Phase II Phase III planned (not yet recruiting) | NCT03583164 NCT05101187 |
VL-2397 | Aspergillus spp. and some Candida spp. | IV | Vical Biotechnology | No current development plans (phase II trial terminated early, because of a business decision) | NCT03327727 |
Aureobasidin A | Board spectrum and proliferative tachyzoite form of toxoplasma (antiprotozoal) | PO/IV | Takara Bio Group | Preclinical | Not available |
MGCD290 | Candida spp. and Aspergillus spp. | PO | MethylGene, Inc. | Further development suspended after phase II clinical trial | NCT01497223 |
VT-1129 | Candida spp. and Cryptococus spp. | PO | Viamet Pharmaceuticals Inc. | Preclinical | Not available |
VT-1161 | Candida spp., coccidioides spp., and Rhizopus spp. | PO | Mycovia Pharmaceuticals | Phase III completed | NCT03561701 |
VT-1598 | Candida spp., Aspergillus spp., and Cryptococus spp. | PO | Mycovia Pharmaceuticals Clinical trial sponsored by National Institute of Allergy and Infectious Diseases (NIAID) | Phase I | NCT04208321 |
Ibrexafungerp | Candida spp. and Aspergillus spp. | PO/IV | Scynexis, Inc. | Phase III | NCT03059992 |
Isavuconazole | Broad spectrum | PO (Isavuconazonium sulfate PO/IV) | Basilea and Astellas Clinical trials sponsored by Memorial Sloan Kettering Cancer Center and M.D. Anderson Cancer Center, respectively. | Phase II trials completed FDA approved in 2015 for the treatment of aspergillosis and invasive mucormycosis | NCT03149055 NCT03019939 |
Albaconazole | Broad spectrum | PO | Palau Pharma Clinical trial sponsored by GSK | Phase II completed | NCT00730405 |
Iodiconazole | Broad spectrum | Topical | Second Military Medical University and Anhui Jiren Pharmaceutical | Phase III (as stated in [58], but no actual data available in the literature) | Not available |
BSG005 | Broad spectrum | IV | Biosergen AS | Phase I | NCT04921254 |
Rezafungin | Candida spp., Aspergillus spp., and Pneumocystis jirovecii | IV | Cidara Therapeutics, Inc. | Phase III | NCT03667690 NCT04368559 |
SUBA-itraconazole | Broad spectrum | PO | Mayne Pharma Ltd. | Phase II FDA approved in 2018 for the treatment of aspergillosis, histoplasmosis, and blastomycosis in patients contraindicated to amphotericin B | NCT03572049 |
Topical terbinafine solution | Onychomycosis | Topical 10% solution | Moberg Pharma | Phase III | NCT02859519 |
Amphotericin B cochleate | Broad spectrum | PO | Matinas BioPharma | Phase II | NCT02629419 |
Structural Type | General Structure * | Target | Ref. |
---|---|---|---|
Phloeodictine analogues | Fungal ergosterol biosynthesis | [59] | |
Biphenylethylaminoacetamides | Fungal cell wall integrity | [60] | |
Thiazoyl guanidine derivatives | Fungal ergosterol biosynthesis | [61] | |
Carboline HDAC inhibitors | Fungal histone deacetylase | [62] | |
Acyl hydrazides | Fungal fatty acid biosynthesis | [64] | |
Thiobenzoate scaffolds | Dual target: fungal acetohydroxyacid synthase and NLRP3 inflammasome | [65] |
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Bouz, G.; Doležal, M. Advances in Antifungal Drug Development: An Up-To-Date Mini Review. Pharmaceuticals 2021, 14, 1312. https://doi.org/10.3390/ph14121312
Bouz G, Doležal M. Advances in Antifungal Drug Development: An Up-To-Date Mini Review. Pharmaceuticals. 2021; 14(12):1312. https://doi.org/10.3390/ph14121312
Chicago/Turabian StyleBouz, Ghada, and Martin Doležal. 2021. "Advances in Antifungal Drug Development: An Up-To-Date Mini Review" Pharmaceuticals 14, no. 12: 1312. https://doi.org/10.3390/ph14121312