AK59 is a STING degrader leveraging HERC4, a HECT-domain E3 ligase [1]. AK59 inhibits the cGAS/STING signaling pathway by promoting STING degradation through the ubiquitin-proteasome system (UPS) [2]. AK59 is frequently used in biochemical experiments to screen STING inhibitors and STING mutant-specific degraders [3].
References:
[1] Mutlu M, Schmidt I, Morrison A I, et al. Small molecule induced STING degradation facilitated by the HECT ligase HERC4[J]. Nature communications, 2024, 15(1): 4584.
[2] Zhang Y, Li L, Xu J, et al. A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders[J]. Molecules, 2026, 31(3): 459.
[3] Zhao H Y, Zhang L, Liu Z, et al. Design of potent small-molecule stimulator of interferon gene inhibitor and stimulator of interferon gene mutant-specific degrader[J]. Journal of Medicinal Chemistry, 2025, 68(11): 11100-11126.
AK59是一种通过HERC4（一种HECT结构域E3连接酶）发挥作用的STING降解剂[1]。AK59通过泛素-蛋白酶体系统（UPS）促进STING降解，从而抑制cGAS/STING信号通路[2]。AK59被广泛用于生化实验中，以筛选STING抑制剂和STING突变体特异性降解剂[3]。