Recilisib (Ex-RAD) is a radiation protection agent that can activate the activities of AKT and PI3K in cells [1]. Recilisib can promote autophagy, enhance cell viability, and reduce cell apoptosis by activating the PI3K/AKT/mTOR pathway [2]. Recilisib can alter the cell cycle distribution pattern of cancer cells receiving radiotherapy and can be used for the treatment of acute radiation syndrome [3].
In vitro, treatment with Recilisib (10μM; 24h) significantly upregulated the protein expressions of p-PI3K, p-AKT, and p-p65 in Caco-2 cells, while the number of apoptotic cells increased, Bax and C-caspase3 expressions were upregulated, and Bcl-2 expression was decreased [4]. Treatment with Recilisib (50μM; 24h) reversed the autophagy induced by MG-132 in vascular smooth muscle cells (VSMCs), and reduced the expressions of autophagy-related proteins p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR [5].
In vivo, treatment with Recilisib (10mg/kg/day; 7 days; i.p.) exacerbated the damage to the integrity of the blood-brain barrier in a mouse model of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, reduced the expressions of ZO-1 and Claudin-5, and had no significant effect on the neurological damage of the mice [6]. Treatment with Recilisib (3, 100, 50, and 10mg/kg/day; i.p.) significantly increased the content of gallstones in a mouse model treated with LPS and aggravated the damage to the gallbladder mucosa [7].
References:
[1] Kang AD, et al. ON01210.Na (Ex-RAD) mitigates radiation damage through activation of the AKT pathway. PLoS One. 2013;8(3):e58355.
[2] Geng X, Zou Y, Li J, et al. BDNF alleviates Parkinson's disease by promoting STAT3 phosphorylation and regulating neuronal autophagy[J]. Cell and Tissue Research, 2023, 393(3): 455-470.
[3] Kamran M Z, Ranjan A, Kaur N, et al. Radioprotective agents: strategies and translational advances[J]. Medicinal research reviews, 2016, 36(3): 461-493.
[4] Niu M, Yin L, Duan T, et al. Asperosaponin VI alleviates TNBS-induced Crohn's disease-like colitis in mice by reducing intestinal epithelial cell apoptosis via inhibiting the PI3K/AKT/NF-κB signaling pathway[J]. Nan fang yi ke da xue xue bao= Journal of Southern Medical University, 2024, 44(12): 2335-2346.
[5] Shu Z, Li X, Zhang W, et al. MG-132 activates sodium palmitate-induced autophagy in human vascular smooth muscle cells and inhibits senescence via the PI3K/AKT/mTOR axis[J]. Lipids in health and disease, 2024, 23(1): 282.
[6] Gong Z, Lao D, Wu Y, et al. Inhibiting PI3K/Akt-Signaling pathway improves neurobehavior changes in anti-NMDAR encephalitis mice by ameliorating blood–brain barrier disruption and neuronal damage[J]. Cellular and Molecular Neurobiology, 2023, 43(7): 3623-3637.
[7] Yu J, Meng Z, Liu X, et al. Lipopolysaccharide in bile promotes the neutrophil extracellular Traps-Induced gallstone formation by activating the gallbladder immune barrier[J]. ImmunoTargets and Therapy, 2024: 789-803.
Recilisib (Ex-RAD)是一种辐射防护剂，可以激活细胞中AKT和PI3K的活性 [1]。Recilisib能够通过激活PI3K/AKT/mTOR通路促进自噬、提高细胞活力并减少细胞凋亡 [2]。Recilisib能够改变接受放射治疗的癌细胞的细胞周期分布模式，可用于治疗急性放射综合征 [3]。
在体外，Recilisib（10μM; 24h）处理显著上调了Caco-2细胞中p-PI3K、p-AKT及p-p65蛋白表达，同时细胞凋亡数量增加，Bax和C-caspase3表达上调，Bcl-2表达降低 [4]。Recilisib（50μM; 24h）处理逆转了MG-132诱导的血管平滑肌细胞（VSMC）自噬，降低了自噬相关蛋白p-PI3K/PI3K、p-AKT/AKT和p-mTOR/mTOR的表达 [5]。
在体内，Recilisib（10mg/kg/day; 7 days; i.p.）处理加剧了抗N-methyl-d-aspartate receptor（NMDAR）脑炎小鼠模型血脑屏障完整性的损害，降低了ZO-1和Claudin-5表达，而对小鼠神经损伤无明显影响 [6]。Recilisib（3, 100, 50和10mg/kg/day; i.p.）显著增加了LPS治疗的胆结石小鼠模型的胆结石含量并加重了胆囊黏膜损伤 [7]。