PF-05231023
(Synonyms: Mal-PEG2-AZD) 目录号 : GC31495
PF-05231023是一种长效成纤维细胞生长因子21（FGF21）类似物。
Cas No.:1037589-69-7
Sample solution is provided at 25 µL, 10mM.
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]。
| Cell experiment [1]: | |
Cell lines | 661W cells |
Preparation Method | To monitor HIF transcriptional activity, a HIF-luciferase reporter gene construct was transfected into the mouse 661W cell line. This construct encodes the firefly luciferase gene, which is regulated by a hypoxia-associated element linked to HIF. CMV-Renilla luciferase was also co-transfected into these cells as an internal control. Prior to measuring luminescence, HIF activation was induced by intracellular administration of cobalt chloride (CoCl2, 200μM, cobalt(II) chloride hexahydrate) to induce normoxia. To assess the inhibitory effects of a long-acting FGF21 molecule (PF-05231023) and pemafibrate on HIF activation, both drugs were added simultaneously with CoCl2 administration. Fluorescence intensity was measured using a dual-luciferase reporter assay system (Promega). The inhibitory effects of pemafibrate and PF-05231023 on HIF activation were assessed 24 hours after induction. |
Reaction Conditions | 0.2nM, 2nM; 24h |
Applications | PF-05231023 significantly inhibited HIF activity. |
| Animal experiment [2]: | |
Animal models | Atherosclerosis mice model |
Preparation Method | Mice were randomly divided into the Apoe−/− + WD + PF-05231023 group (n = 6) and the Apoe−/− + WD + saline group (n = 6). Both groups of mice were fed WD for 12 weeks to establish an atherosclerosis model, followed by 7 weeks of intraperitoneal injection of 10mg/kg PF-05231023 or an equal volume of saline. C57BL/6 female mice fed a control diet (WT + Control) served as a healthy control group (n = 6), and Apoe−/− mice fed a control diet (Apoe−/− + Control) served as a transgenic control group (n = 6). |
Dosage form | 10mg/kg; ip; 7 weeks |
Applications | PF-05231023 effectively improves lipid metabolism in Apoe−/− mice and has anti-atherosclerotic effects. |
References: | |
| Cas No. | 1037589-69-7 | SDF | |
| 别名 | Mal-PEG2-AZD | ||
| Canonical SMILES | O=C(CCN1C(C=CC1=O)=O)NCCOCCOCCC(NC2=CC=C(C=C2)CCC(N3C(CC3)=O)=O)=O | ||
| 分子式 | C26H32N4O8 | 分子量 | 528.55 |
| 溶解度 | DMSO : 125 mg/mL (236.50 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.892 mL | 9.4598 mL | 18.9197 mL |
| 5 mM | 378.4 μL | 1.892 mL | 3.7839 mL |
| 10 mM | 189.2 μL | 946 μL | 1.892 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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- Purity: >98.50%
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