Gln-AMS is an aminoacyl-tRNA synthetase (AARS) inhibitor, with the Ki value of 1.32μM [1]. Gln-AMS inhibits ferroptosis in hyperglycemic cells by simultaneously suppressing the expression of AARS1 and H3K18la [2]. Gln-AMS is widely used as a potent and synergistic immunosuppressant to regulate the allogeneic mixed lymphocyte reaction [3].
In vitro, Gln-AMS (10μM) treatment for 12 hours significantly inhibited the accumulation of Kla in lactate-induced mouse primary hippocampal neurons neuron cells and the lactylation of ATR-interacting protein (ATRIP), as well as the ATR/CHK1 signaling pathway [4].
References:
[1] Rath V L, Silvian L F, Beijer B, et al. How glutaminyl-tRNA synthetase selects glutamine[J]. Structure, 1998, 6(4): 439-449.
[2] Hong J, Xu H, Yu L, et al. AARS1-mediated lactylation of H3K18 and STAT1 promotes ferroptosis in diabetic nephropathy[J]. Cell Death & Differentiation, 2026, 33(3): 589-604.
[3] Van de Vijver P, Ostrowski T, Sproat B, et al. Aminoacyl-tRNA synthetase inhibitors as potent and synergistic immunosuppressants[J]. Journal of medicinal chemistry, 2008, 51(10): 3020-3029.
[4] Luo S, Lyu Z, Huang H, et al. Targeting AARS1-dependent lactylation improves neuronal process plasticity and mitigates cognitive deficits in sepsis-associated encephalopathy[J]. Brain, Behavior, and Immunity, 2026: 106493.