Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia.
Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia.
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DOI：
10.1186/s12933-017-0602-y
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发表时间：
2017-10-04
影响因子：
9.3
通讯作者：
Fruchart JC
中科院分区：
文献类型：
--
作者：
Fruchart JC
尽管有包括他汀类药物在内的最佳循证治疗，但残余心血管风险对二十一世纪的临床医生构成了重大挑战。致动脉粥样硬化血脂异常，特别是甘油三酯升高（富含甘油三酯的脂蛋白及其残余物增加的标志物）是导致脂质相关残留风险的重要因素，特别是在胰岛素抵抗性疾病（例如2型糖尿病）中。目前的治疗选择包括过氧化物酶体增殖物激活受体 α (PPARα) 激动剂（贝特类药物），但这些药物对 PPARα 的效力较低且选择性有限。调节独特的受体-辅因子结合谱来识别诱导 PPARα 介导的有益作用的最有效分子，同时避免不需要的副作用，提供了一种新的治疗方法，并为开发新型选择性 PPARα 调节剂 (SPPARMα) pemafibrate (K-877, Parmodia™) 提供了理论基础。在临床试验中，培马贝特无论是作为单一疗法还是作为他汀类药物的附加疗法，均可有效治疗致动脉粥样硬化性血脂异常，并显着降低甘油三酯、残余胆固醇和载脂蛋白 CIII。 Pemafibrate 还可以增加血清成纤维细胞生长因子 21，与代谢稳态有关。对肝或肾功能没有临床意义的不良影响，包括没有相关的血清肌酐升高。一项名为“PROMINENT”的主要结果研究将明确评估 Pemafibrate 在管理尽管接受他汀类药物治疗但患有动脉粥样硬化血脂异常的 2 型糖尿病患者中残余心血管风险方面的作用。
Despite best evidence-based treatment including statins, residual cardiovascular risk poses a major challenge for clinicians in the twenty first century. Atherogenic dyslipidaemia, in particular elevated triglycerides, a marker for increased triglyceride-rich lipoproteins and their remnants, is an important contributor to lipid-related residual risk, especially in insulin resistant conditions such as type 2 diabetes mellitus. Current therapeutic options include peroxisome proliferator-activated receptor alpha (PPARα) agonists, (fibrates), but these have low potency and limited selectivity for PPARα. Modulating the unique receptor–cofactor binding profile to identify the most potent molecules that induce PPARα-mediated beneficial effects, while at the same time avoiding unwanted side effects, offers a new therapeutic approach and provides the rationale for development of pemafibrate (K-877, Parmodia™), a novel selective PPARα modulator (SPPARMα). In clinical trials, pemafibrate either as monotherapy or as add-on to statin therapy was effective in managing atherogenic dyslipidaemia, with marked reduction of triglycerides, remnant cholesterol and apolipoprotein CIII. Pemafibrate also increased serum fibroblast growth factor 21, implicated in metabolic homeostasis. There were no clinically meaningful adverse effects on hepatic or renal function, including no relevant serum creatinine elevation. A major outcomes study, PROMINENT, will provide definitive evaluation of the role of pemafibrate for management of residual cardiovascular risk in type 2 diabetes patients with atherogenic dyslipidaemia despite statin therapy.
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DOI：
10.1056/nejmoa1001288
发表时间：
2010-07-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;ACCORD Eye Study Group;Chew EY;Ambrosius WT;Davis MD;Danis RP;Gangaputra S;Greven CM;Hubbard L;Esser BA;Lovato JF;Perdue LH;Goff DC Jr;Cushman WC;Ginsberg HN;Elam MB;Genuth S;Gerstein HC;Schubart U;Fine LJ
通讯作者：
Fine LJ
影响因子：
9.3
作者：
Fruchart JC;Davignon J;Hermans MP;Al-Rubeaan K;Amarenco P;Assmann G;Barter P;Betteridge J;Bruckert E;Cuevas A;Farnier M;Ferrannini E;Fioretto P;Genest J;Ginsberg HN;Gotto AM Jr;Hu D;Kadowaki T;Kodama T;Krempf M;Matsuzawa Y;Núñez-Cortés JM;Monfil CC;Ogawa H;Plutzky J;Rader DJ;Sadikot S;Santos RD;Shlyakhto E;Sritara P;Sy R;Tall A;Tan CE;Tokgözoğlu L;Toth PP;Valensi P;Wanner C;Zambon A;Zhu J;Zimmet P;Residual Risk Reduction Initiative (R3i)
通讯作者：
Residual Risk Reduction Initiative (R3i)
影响因子：
158.5
作者：
Barter, Philip J.;Caulfield, Mark;Brewer, Bryan
通讯作者：
Brewer, Bryan
DOI：
10.1016/s2213-8587(14)70102-0
发表时间：
2014-08
期刊：
The lancet. Diabetes & endocrinology
影响因子：
--
作者：
Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration
通讯作者：
Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration
影响因子：
8.2
作者：
Davis, T. M. E.;Ting, R.;Keech, A. C.
通讯作者：
Keech, A. C.