title: CD101: a novel long-acting echinocandin.
abstract: CD101 is a novel echinocandin drug being developed to treat severe fungal infections including invasive candidiasis. We have performed a series of studies to evaluate the antifungal properties of CD101 against both echinocandin-susceptible and -resistant Candida strains. Antifungal susceptibility testing performed on a collection of 95 Candida strains including 30 caspofungin-resistant isolates containing fks mutations demonstrated comparable antifungal potency of CD101 relative to micafungin (MCF) across different Candida species. Comparable kinetic inhibition of glucan synthase activity was also observed for CD101 and MCF on both wild-type (WT) and resistant fks mutant Candida strains. Similarly, both drugs yielded nearly identical values for a mutant prevention concentration. In a murine model of invasive candidiasis, CD101 displayed better or at least comparable efficacy relative to MCF in treating WT or fks mutant Candida albicans. An exceptional long-lived pharmacokinetic profile was observed in mice following a single dose of CD101. Collectively, CD101 has great potential not only in treating invasive Candida infections but also in preventing emergence of resistance to currently approved echinocandin drugs.
authors.affiliation: Public Health Research Institute, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Public Health Research Institute, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Winder B
authors.initials: WB
authors.lastname: Perez
authors.affiliation: Public Health Research Institute, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jiménez-Ortigosa
authors.affiliation: Cidara Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Grayson
authors.initials: G
authors.lastname: Hough
authors.affiliation: Cidara Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Locke
authors.affiliation: Cidara Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Voon
authors.initials: V
authors.lastname: Ong
authors.affiliation: Cidara Therapeutics, Inc., San Diego, CA, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Bartizal
authors.affiliation: Public Health Research Institute, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, NJ, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D020128:Inhibitory Concentration 50; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; C000621306:CD101 echinocandin; D054714:Echinocandins