ArticleAntimicrobial agents and chemotherapy2004
Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 35 citations in OpenAlex.
- Research progress on the function and regulatory pathways of amino acid permeases in fungi.World journal of microbiology & biotechnology · 2024Review
- Aminoacyl-tRNA synthetases as therapeutic targets.Nature reviews. Drug discovery · 2019Review
- Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets.International journal of molecular sciences · 2018Review
- Oropharyngeal candidiasis in children with lymphohematopoietic malignancies in Mashhad, Iran.Current medical mycology · 2015Article
- Genetic validation of aminoacyl-tRNA synthetases as drug targets in Trypanosoma brucei.Eukaryotic cell · 2014Article
- Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design.Nucleic acids research · 2010Article
- IA, database of known ligands of aminoacyl-tRNA synthetases.Journal of computer-aided molecular design · 2007Article
- In vitro activity and in vivo efficacy of icofungipen (PLD-118), a novel oral antifungal agent, against the pathogenic yeast Candida albicans.Antimicrobial agents and chemotherapy · 2006Article
- Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents.Antimicrobial agents and chemotherapy · 2005Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P </= 0.05, P </= 0.01, P </= 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis.
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