Pim1/AKK1-IN-1 is a potent multi-kinase inhibitor that exerts inhibitory effects on kinases including Pim1, AKK1 (AAK1), LKB1 and MST2[1]. These kinases play key roles in regulating cell proliferation-apoptosis balance, endocytic transport, and energy metabolism[2][3]. Pim1/AKK1-IN-1 is usually used in metabolic and viral infection-related research[4][5].
In vitro, Pim1/AKK1-IN-1 (10-1000nM; 48h) dose-dependently reversed NaB-induced suppression of STAT6 phosphorylation, nuclear translocation, and IL-4R recruitment in bone marrow-derived macrophages[6].
In vivo, Pim1/AKK1-IN-1 (40mg/kg; single intraperitoneal injection) exacerbated DSS-induced colitis in mice, increased colonic UGT1A4 levels and bile acid accumulation, caused greater weight loss compared to DSS treatment alone[7].
References:
[1] Bamborough P, Drewry D, Harper G, Smith GK, Schneider K. Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. J Med Chem. 2008;51(24):7898-7914.
[2] Trelford CB, Shepherd TG. LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors. Cell Commun Signal. 2024;22(1):310.
[3] Xin X, Wang Y, Zhang L, et al. Development and therapeutic potential of adaptor-associated kinase 1 inhibitors in human multifaceted diseases. Eur J Med Chem. 2023;248:115102.
[4] Zhou B, Luo Y, Ji N, Hu C, Lu Y. Orosomucoid 2 maintains hepatic lipid homeostasis through suppression of de novo lipogenesis. Nat Metab. 2022;4(9):1185-1201.
[5] Garcia-Carceles J, Caballero E, Gil C, Martinez A. Kinase Inhibitors as Underexplored Antiviral Agents. J Med Chem. 2022;65(2):935-954.
[6] Liang W, Wu H, Long Q, et al. LKB1 activated by NaB inhibits the IL-4/STAT6 axis and ameliorates renal fibrosis through the suppression of M2 macrophage polarization. Life Sci. 2025;370:123564.
[7] Lin Z, Feng Y, Wang J, Men Z, Ma X. Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea. Microbiome. 2025;13(1):36.
Pim1/AKK1-IN-1是一种有效的多靶点抑制剂，对Pim1、AKK1（AAK1）、LKB1和MST2等激酶具有抑制作用[1]。这些激酶在调节细胞增殖-凋亡平衡、内吞运输和能量代谢中起关键作用[2][3]。Pim1/AKK1-IN-1通常用于代谢和病毒感染相关研究[4][5]。
体外实验中，Pim1/AKK1-IN-1（10-1000nM; 48h）呈剂量依赖性逆转了NaB诱导的骨髓源性巨噬细胞中STAT6磷酸化、核易位和IL-4R募集的抑制[6]。
体内实验中，与单独DSS处理相比，Pim1/AKK1-IN-1 （40mg/kg；单次腹腔注射）加重DSS诱导的小鼠结肠炎，增加结肠UGT1A4水平和胆汁酸积累，引起更大的体重减轻[7]。