TY - JOUR
T1 - An insight into the antifungal pipeline
T2 - Selected new molecules and beyond
AU - Ostrosky-Zeichner, Luis
AU - Casadevall, Arturo
AU - Galgiani, John N.
AU - Odds, Frank C.
AU - Rex, John H.
N1 - Funding Information:
J.N.G. acknowledges that this research was supported by NIH/NIAID grant AI065359 of the Pacific Southwest Regional Center of Excellence for Biodefense and Emerging Infectious Disease.
Funding Information:
The existing supply of nikkomycin Z was found to be suitable for continued clinical use and was used to conduct a phase I multi-dose safety trial, with subjects receiving 250 mg twice daily to 750 mg three times daily for 14 days. All subjects have completed drug administration, and preliminary evaluation has not identified any safety concerns. Full safety analysis and pharmacokinetics should be available in 2010. other work that is currently underway by the University of Arizona and a small start-up company (valley Fever Solutions) is directed at more fully defining the pharmacokinetics and pharmacodynamics in experimental murine infections. This will assist in clinical trial design and the development of a new, less expensive manufacturing process for use in future clinical trials. These studies have been supported by awards from the US national Institutes of Health (nIH), the FDA office of orphan Drug Development and the JT Tai and Company Foundation. A US$3 million small-business grant has recently been awarded by the nIH to support further drug manufacturing and a phase II clinical trial in patients with early coccidioidal pneumonia.
PY - 2010/9
Y1 - 2010/9
N2 - Invasive fungal infections are increasing in incidence and are associated with substantial mortality. Improved diagnostics and the availability of new antifungals have revolutionized the field of medical mycology in the past decades. This Review focuses on recent developments in the antifungal pipeline, concentrating on promising candidates such as new azoles, polyenes and echinocandins, as well as agents such as nikkomycin Z and the sordarins. Developments in vaccines and antibody-based immunotherapy are also discussed. Few therapeutic products are currently in active development, and progression of therapeutic agents with fungus-specific mechanisms of action is of key importance.
AB - Invasive fungal infections are increasing in incidence and are associated with substantial mortality. Improved diagnostics and the availability of new antifungals have revolutionized the field of medical mycology in the past decades. This Review focuses on recent developments in the antifungal pipeline, concentrating on promising candidates such as new azoles, polyenes and echinocandins, as well as agents such as nikkomycin Z and the sordarins. Developments in vaccines and antibody-based immunotherapy are also discussed. Few therapeutic products are currently in active development, and progression of therapeutic agents with fungus-specific mechanisms of action is of key importance.
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U2 - 10.1038/nrd3074
DO - 10.1038/nrd3074
M3 - Review article
C2 - 20725094
AN - SCOPUS:77956343542
SN - 1474-1776
VL - 9
SP - 719
EP - 727
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 9
ER -