PF-04620110
(Synonyms: PF 04620110,PF04620110) 目录号 : GC15274
PF-04620110是一种口服有效的选择性二酰甘油酰基转移酶-1（DGAT1）抑制剂（IC50 = 19nM）。
Cas No.:1109276-89-2
Sample solution is provided at 25 µL, 10mM.
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PF-04620110 is an orally active, selective diacylglycerol acyltransferase-1 (DGAT1) inhibitor (IC50 = 19nM) [1]. PF-04620110 blocks triglyceride synthesis by inhibiting DGAT-1, thereby lowering plasma triglyceride levels in vivo [2]. PF-04620110 is commonly used to treat diabetes [3-4].
In MDA-MB-231 cells, PF-04620110 (5µM; 24h) blocks the conversion of diacylglycerol to triacylglycerol to inhibit lipid droplet formation [5]. In MCF10CA1a cells, PF-04620110 (50µM; 24h) reduces triacylglycerol storage and restricts cell migration [6].
In high-fat diet mice model, PF-04620110 (3mg/kg; po; 4 weeks) suppressed fatty acid induced NLRP3 inflammasome activation [7]. In high-fat diet cynomolgus monkeys model, PF-04620110 (0.1-1mg/kg; po; 4d) treatment induced diarrhea [8].
References:
[1]. Dow R L, Li J C, Pence M P, et al. Discovery of PF-04620110, a potent, selective, and orally bioavailable inhibitor of DGAT-1[J]. ACS medicinal chemistry letters, 2011, 2(5): 407-412.
[2]. Dow R L, Andrews M, Aspnes G E, et al. Design and synthesis of potent, orally-active DGAT-1 inhibitors containing a dioxino [2, 3-d] pyrimidine core[J]. Bioorganic & medicinal chemistry letters, 2011, 21(20): 6122-6125.
[3]. Dow R L, Andrews M P, Li J C, et al. Defining the key pharmacophore elements of PF-04620110: discovery of a potent, orally-active, neutral DGAT-1 inhibitor[J]. Bioorganic & Medicinal Chemistry, 2013, 21(17): 5081-5097.
[4]. Enayetallah A E, Ziemek D, Leininger M T, et al. Modeling the mechanism of action of a DGAT1 inhibitor using a causal reasoning platform[J]. PloS one, 2011, 6(11): e27009.
[5]. Almanza A, Mnich K, Blomme A, et al. Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer[J]. Nature communications, 2022, 13(1): 2493.
[6]. Andolino C, Cotul E K, Xianyu Z, et al. Fatty acid synthase-derived lipid stores support breast cancer metastasis[J]. Cancer & metabolism, 2025, 13(1): 35.
[7]. Jo S I, Bae J H, Kim S J, et al. PF-04620110, a potent antidiabetic agent, suppresses fatty acid-induced NLRP3 inflammasome activation in macrophages[J]. Diabetes & Metabolism Journal, 2019, 43(5): 683.
[8]. Cheng D, Zinker B A, Luo Y, et al. MGAT2 inhibitor decreases liver fibrosis and inflammation in murine NASH models and reduces body weight in human adults with obesity[J]. Cell Metabolism, 2022, 34(11): 1732-1748. e5.
PF-04620110是一种口服有效的选择性二酰甘油酰基转移酶-1（DGAT1）抑制剂（IC50 = 19nM） [1]。PF-04620110通过抑制DGAT-1来阻断甘油三酯的合成，从而降低体内血浆甘油三酯水平 [2]。PF-04620110常用于治疗糖尿病 [3-4]。
在MDA-MB-231细胞中，PF-04620110（5µM; 24h）可阻断二酰甘油转化为三酰甘油，从而抑制脂滴形成 [5]。在MCF10CA1a细胞中，PF-04620110（50µM; 24h）可减少三酰甘油的储存并限制细胞迁移 [6]。
在高脂饮食小鼠模型中，PF-04620110（3mg/kg；po；4周）抑制了脂肪酸诱导的NLRP3炎症小体活化 [7]。在高脂饮食食蟹猴模型中，PF-04620110（0.1-1mg/kg；po；4d）治疗诱发腹泻 [8]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 cells |
Preparation Method | MDA-MB-231 cells were cultured in DMEM high-glucose medium supplemented with 10% fetal bovine serum (FBS) and 2mM L-glutamine in a humidified incubator at 37℃ and 5% CO2. Cells were seeded at appropriate density and treated with 20µM MKC8866, 5µM PF-04620110, or an equal volume of DMSO 24 hours later. |
Reaction Conditions | 5µM; 24h |
Applications | PF-04620110 blocks the conversion of diacylglycerol to triacylglycerol to inhibit lipid droplet formation. |
| Animal experiment [2]: | |
Animal models | High-fat diet (HFD) mice model |
Preparation Method | C57BL/6J mice (male, 6 weeks old) with similar plasma glucose levels and body weights were used. For generation of HFD‐induced diabetic mice, C57BL/6J mice were fed HFD with 0.15% cholesterol (HFD, 21% crude fat, 0.15% cholesterol, and 19.5% casein) or regular diet (RD), for 12 weeks. For treatment of PF-04620110, PF-04620110 or vehicle control (dimethyl sulfoxide [DMSO]) were fed once a day at the dose of 3mg/kg for another 4 weeks. |
Dosage form | 3mg/kg; po; 4 weeks |
Applications | PF-04620110 suppressed fatty acid induced NLRP3 inflammasome activation. |
References: | |
| Cas No. | 1109276-89-2 | SDF | |
| 别名 | PF 04620110,PF04620110 | ||
| 化学名 | 2-[4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-yl)phenyl]cyclohexyl]acetic acid | ||
| Canonical SMILES | C1CC(CCC1CC(=O)O)C2=CC=C(C=C2)N3CCOC4=NC=NC(=C4C3=O)N | ||
| 分子式 | C21H24N4O4 | 分子量 | 396.44 |
| 溶解度 | ≥ 16.9mg/mL in DMSO | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet