Table 1 List of characterized AARS inhibitors.
From: Structural basis for full-spectrum inhibition of translational functions on a tRNA synthetase
Categories | Inhibitors | K i /IC 50 /Kd | Activities |
|---|---|---|---|
Type Ia: Mimetics binding amino acid and/or ATP-binding pocket | Mupirocin—IleRS | 2.5–32 nM | E. coli, yeast, Ps.fluorescens, rat, IleRS ATP/[32P]-pyrophosphate exchange (ATP-PPi exchange) and aminoacylation51,52 B. subtilis and S. aureus IleRS mupirocin uptake53 |
|  | Ile-ol-AMP | 30 nM | S. aureus IleRS stop-flow fluorescence54 |
|  | Thr-AMS–ThrRS | ~13 nM | E. coli and human ThrRS ATP-PPi exchange55 |
|  | 10a–ThrRS | ~3 nM | E. coli and human ThrRS ATP-PPi exchange55 |
|  | Cladosporin–LysRS | 40–90 nM | Plasmodium parasites growth56 |
|  |  | 74.3 μM | Human Hela cell growth56 |
|  | Indolmycin–TrpRS | 160 nM | S. aureus Tryptophan uptake57 |
|  | Agrocin 84–LeuRS | <10 nM | A. tumefaciens LeuRS aminoacylation58 |
|  | SB217452–SerRS | 8 nM | S. aureus and rat SerRS aminoacylation59 |
Type Ib: Mimetics binding amino acid and tRNA-binding pockets | HF–ProRS | 2.5–18.3 nM | T-cell proliferation in response to alloantigen or IL-2 (ref. 60); P. berghei sporozoite load in HepG2 cells61; Human ProRS aminoacylation45 |
Type Ic: Trapping tRNA at editing site | AN2690–LeuRS | 1.85 μM | Yeast LeuRS aminoacylation39 |
|  | ZCL039–LeuRS | 1.73 μM | S. pneumoniae LeuRS aminoacylation62 |
Type II: Non-mimetic, blocking all substrate binding by geometrical fitting | BN–ThrRS | 0.8–7 nM | Rat aorta tube formation11; Plasmodium growth10; E. coli and S. solfataricus ThrRS ATP-PPi exchange20 Human ThrRS aminoacylation (this study) |
