Wołowiec Łukasz, Osiak Joanna, Wołowiec Anna, Wijata Aleksandra, Grześk Elżbieta, Kozakiewicz Mariusz, Banach Joanna, Nowaczyk Alicja, Nowaczyk Jacek, Grześk Grzegorz
Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland.
Department of Geriatrics, Division of Biochemistry and Biogerontology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland.
Pharmaceutics. 2023 Jan 18;15(2):323. doi: 10.3390/pharmaceutics15020323.
Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research.
血脂异常被列为重要的心血管疾病危险因素之一。治疗脂质紊乱颇具难度，而在心血管疾病的二级和一级预防中，使低密度脂蛋白胆固醇（LDL-C）达到理想水平至关重要。多年来，他汀类药物一直是降脂治疗的基础。然而，由于其副作用以及达到推荐的LDL-C值的严格标准，这些药物往往并不充分。即便添加其他药物，如依折麦布，也无助于实现LDL-C目标值。前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）的发现引发了对一类新型蛋白质类药物的深入研究。PCSK9蛋白主要位于肝细胞中，参与LDL-C的代谢。起初，发明了针对PCSK9蛋白的抗体，如阿利西尤单抗。接下来是英克西兰。英克西兰是一种小干扰RNA（siRNA），它通过特异性结合PCSK9蛋白的mRNA前体并使其降解来抑制PCSK9的表达。近年来人们注意到，siRNA是生物医学研究和药物发现的有力工具。这项工作的目的是总结英克西兰的分子机制、药代动力学、药效学，并综述最新研究。
