慢性病中的达帕格利弗洛辛:来自网络药理学和分子对接模拟的见解
Atthaphong Phongphithakchai1, Aman Tedasen2,3, Ratana Netphakdee2
1Nephrology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Life (Basel, Switzerland)
|March 27, 2025
概括
达帕格利弗洛辛通过向与炎症和氧化应激有关的多个途径,显示出治疗慢性病 (CKD) 的潜力. 这项研究澄清了其分子机制,以改善CKD管理.
科学领域:
- 药理学 药理学是指药理学的学科.
- 腎臟病學 (nephrology) 是一種醫學專業.
- 计算生物学 计算生物学
背景情况:
- 慢性病 (CKD) 的特点是炎症,氧化应激和纤维化,导致功能障碍.
- 作为SGLT2抑制剂的达帕格利弗洛辛 (Dapagliflozin) 提供了超出血糖控制的保护性益处,但其在CKD中的确切分子机制需要阐明.
研究的目的:
- 通过网络药理学和分子对接,研究Dapagliflozin在慢性病 (CKD) 中的多目标分子机制.
- 在CKD病原体的背景下,确定Dapagliflozin调节的关键目标和途径.
主要方法:
- 网络药理学方法以确定Dapagliflozin在CKD中的潜在点和途径.
- 分析Dapagliflozin的ADMET特性,并确定常见的目标与CKD.
- 构建蛋白质与蛋白质相互作用 (PPI) 网络和丰富分析 (GO,KEGG).
- 分子对接以验证Dapagliflozin与关键枢纽蛋白的结合亲缘关系.
主要成果:
- 在CKD中确定了208个达帕格利弗洛辛的常见点,包括EGFR,GSK3β和IL-6.
- 富化分析揭示了PI3K-Akt,MAPK和AGE-RAGE等关键通路,这些通路涉及炎症,氧化应激和代谢调节.
- 分子对接证实了达帕格利弗洛辛与像EGFR (-8.42 kcal/mol),GSK3β (-7.70 kcal/mol) 和IL-6 (-6.83 kcal/mol) 这样的枢纽蛋白之间显著的结合亲缘关系.
结论:
- 达帕格利弗洛辛在治疗慢性病 (CKD) 方面显示出多目标治疗潜力.
- 该药物有效调节关键通路,与炎症,氧化应激和CKD中的代谢失调有关.
- 这项研究为达帕格利弗洛辛的保护作用提供了机制基础,支持其在CKD中的临床应用.
相关概念视频
Dipeptidyl Peptidase 4 Inhibitors
146
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
146
Renal Failure: Dose Adjustments
50
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
50
Factors Affecting Renal Clearance: Renal Impairment
44
Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
44
Hormonal Regulation
32.8K
The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
32.8K
Antihypertensive Drugs: Potassium-Sparing Diuretics
424
Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
424
Nonlinear Pharmacokinetics: Bioavailability and Protein-Drug Binding
95
When a drug follows nonlinear pharmacokinetics, its bioavailability, the amount of the drug that reaches the systemic circulation, can change with different doses. This is due to the presence of a saturable pathway. The pathway becomes saturated as the drug concentration increases, decreasing the absorption rate. Consequently, the drug's bioavailability may be lower than expected at higher doses.
To quantify the extent of bioavailability, pharmacologists often use a parameter called .
To quantify the extent of bioavailability, pharmacologists often use a parameter called .
95


