AG-1024 is a reversible, competitive and selective insulin-like growth factor-1 receptor (IGF-1R) inhibitor with an IC50 value of 7µM[1]. AG-1024 can inhibit the phosphorylation of insulin receptor (IR) with an IC50 value of 57µM[2]. AG-1024 can induce cell apoptosis and has anti-cancer activity[3].
In vitro, AG-1024 (5µM) treatment of acquired sorafenib-resistant cell lines (SNU-sora-5 and SK-sora-5 cells) for 72h significantly increased the cytotoxicity of sorafenib, activated the intracellular mTOR/P21 signaling pathway, and enhanced the cell G1/S arrest[4]. AG-1024 (10μM) treatment of PC3 and DU145 cells inhibited cell proliferation and induced cell G2/M phase arrest[5].
In vivo, oral administration of AG-1024 (20mg/kg) to diabetic nephropathy model rats for 8 weeks alleviated metabolic disorders, improved renal function, reduced renal inflammation, and reduced renal fibrosis formation[6].
References:
[1] Xue M, Cao X, Zhong Y, et al. Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors in cancer therapy: advances and perspectives[J]. Current pharmaceutical design, 2012, 18(20): 2901-2913.
[2] Talior-Volodarsky I, Mahou R, Zhang D, et al. The role of insulin growth factor-1 on the vascular regenerative effect of MAA coated disks and macrophage-endothelial cell crosstalk[J]. Biomaterials, 2017, 144: 199-210.
[3] Cheng H Y, Ko F H. Studying the enhancement of programmed cell death by combined AG1024 and paclitaxel in a model of chronic myelogenous leukemia[J]. Life sciences, 2014, 102(2): 118-126.
[4] Zhou W, Lou W, Chen J, et al. AG-1024 Sensitizes Sorafenib-Resistant Hepatocellular Carcinoma Cells to Sorafenib via Enhancing G1/S Arrest[J]. OncoTargets and therapy, 2021: 1049-1059.
[5] Tang Q, Ma J, Sun J, et al. Genistein and AG1024 synergistically increase the radiosensitivity of prostate cancer cells[J]. Oncology Reports, 2018, 40(2): 579-588.
[6] Liu J, Zhang Y, Liu M, et al. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway[J]. Open Medicine, 2023, 18(1): 20230683.
AG-1024是一种可逆的，竞争性和选择性的胰岛素样生长因子-1受体（IGF-1R）抑制剂，IC50值为7µM[1]。AG-1024能够抑制胰岛素受体（IR）的磷酸化，IC50值为57µM[2]。AG-1024能够诱导细胞凋亡，具有抗癌活性[3]。
在体外，AG-1024（5µM）处理获得性索拉非尼耐药细胞系（SNU-sora-5和SK-sora-5细胞）72h，显著提高了索拉非尼对细胞的毒性，激活了细胞内mTOR/P21信号通路，增强了细胞G1/S阻滞[4]。AG-1024（10μM）处理PC3和DU145细胞，抑制了细胞增殖，诱导了细胞G2/M期阻滞[5]。
在体内，AG-1024（20mg/kg）通过口服治疗糖尿病肾病模型大鼠8周，减轻了代谢紊乱，改善了大鼠的肾功能，减轻了肾脏炎症，减少了肾纤维化形成[6]。