PF-05231023 is a long-acting fibroblast growth factor 21 (FGF21) analog [1]. PF-05231023 binds to the FGF21 receptor complex (FGFR1c and Klb), activating downstream signaling pathways that regulate energy metabolism, glucose homeostasis, and lipid metabolism [2-3]. PF-05231023 is primarily used to treat type 2 diabetes, obesity, and lipid metabolism disorders [4].
In 661W cells, PF-05231023 (0.2nM, 2nM; 24h) significantly inhibited HIF activity [5]. In primary human retinal microvascular endothelial cells, PF-05231023 (50ng/mL, 100ng/mL; 4h) prevented the hVEGF-induced increase in cell permeability [6].
In atherosclerosis mice model, PF-05231023 (10mg/kg; ip; 7 weeks) effectively improves lipid metabolism in Apoe−/− mice and has anti-atherosclerotic effects [7]. In ob/ob mice, PF-05231023 (0.03-10mg/kg; sc; 3 weeks) treatment improves glucose excursions during glucose tolerance testing [8].
References:
[1]. Dong J Q, Rossulek M, Somayaji V R, et al. Pharmacokinetics and pharmacodynamics of PF‐05231023, a novel long‐acting FGF21 mimetic, in a first‐in‐human study[J]. British journal of clinical pharmacology, 2015, 80(5): 1051-1063.
[2]. Brunetti L, Kagan L. Harnessing the Action of Fibroblast Growth Factor21 as a Therapeutic Agent[J]. Current pharmacology reports, 2017, 3(1): 26-35.
[3]. Aaldijk A S, Verzijl C R C, Jonker J W, et al. Biological and pharmacological functions of the FGF19-and FGF21-coreceptor beta klotho[J]. Frontiers in endocrinology, 2023, 14: 1150222.
[4]. Talukdar S, Zhou Y, Li D, et al. A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects[J]. Cell metabolism, 2016, 23(3): 427-440.
[5]. Tomita Y, Ozawa N, Miwa Y, et al. Pemafibrate prevents retinal pathological neovascularization by increasing FGF21 level in a murine oxygen-induced retinopathy model[J]. International journal of molecular sciences, 2019, 20(23): 5878.
[6]. Tomita Y, Fu Z, Wang Z, et al. Long-acting FGF21 inhibits retinal vascular leakage in in vivo and in vitro models[J]. International journal of molecular sciences, 2020, 21(4): 1188.
[7]. Zhao J, Liu X, Yue J, et al. PF-05231023 reduces lipid deposition in apolipoprotein E-deficient mice by inhibiting the expression of lipid synthesis genes[J]. Frontiers in Veterinary Science, 2024, 11: 1429639.
[8]. Weng Y, Chabot J R, Bernardo B, et al. Pharmacokinetics (PK), pharmacodynamics (PD) and integrated PK/PD modeling of a novel long acting FGF21 clinical candidate PF-05231023 in diet-induced obese and leptin-deficient obese mice[J]. PloS one, 2015, 10(3): e0119104.
PF-05231023是一种长效成纤维细胞生长因子21（FGF21）类似物 [1]。PF-05231023与FGF21受体复合物（FGFR1c和Klb）结合，激活调节能量代谢、葡萄糖稳态和脂质代谢的下游信号通路 [2-3]。PF-05231023主要用于治疗2型糖尿病、肥胖症和脂质代谢紊乱 [4]。
在661W细胞中，PF-05231023（0.2nM，2nM；24h）显著抑制了HIF活性 [5]。在原代人视网膜微血管内皮细胞中，PF-05231023（50ng/mL，100ng/mL；4h）可抑制hVEGF诱导的细胞通透性增加 [6]。
在动脉粥样硬化小鼠模型中，PF-05231023（10mg/kg；ip；7周）有效改善Apoe−/−小鼠的脂质代谢，具有抗动脉粥样硬化作用 [7]。在ob/ob小鼠中，PF-05231023（0.03-10mg/kg；sc；3周）治疗可改善葡萄糖耐量测试中的血糖波动 [8]。