I should have just given you an abstract
(this is a year old, and I've no idea whether
or not they even have real clinical candidates)
Antimicrob Agents Chemother. 2005 Dec;49(12):4942-9.
Structure-guided discovery of novel aminoglycoside mimetics as antibacterial translation inhibitors.
Zhou Y, Gregor VE, Sun Z, Ayida BK, Winters GC, Murphy D,
Simonsen KB, Vourloumis D, Fish S, Froelich JM, Wall D, Hermann T.
Anadys Pharmaceuticals, San Diego, California, USA.
We report the structure-guided discovery, synthesis, and initial characterization of 3,5-diamino-piperidinyl triazines (DAPT), a novel translation inhibitor class that targets bacterial rRNA and exhibits broad-spectrum antibacterial activity. DAPT compounds were designed as structural mimetics of aminoglycoside antibiotics which bind to the bacterial ribosomal decoding site and thereby interfere with translational fidelity. We found that DAPT compounds bind to oligonucleotide models of decoding-site RNA, inhibit translation in vitro, and induce translation misincorporation in vivo, in agreement with a mechanism of action at the ribosomal decoding site. The novel DAPT antibacterials inhibit growth of gram-positive and gram-negative bacteria, including the respiratory pathogen Pseudomonas aeruginosa, and display low toxicity to human cell lines. In a mouse protection model, an advanced DAPT compound demonstrated efficacy against an Escherichia coli infection at a 50% protective dose of 2.4 mg/kg of body weight by single-dose intravenous administration.
I suppose they'll update their website from time to time
anadyspharma.com
Anadys will consider pursuing further research and development of one or more of these compounds with appropriate partners.
Not much to chew on there. |
