A Non-interventional, Multi Center, Prospective Observational Study to Evaluate the Effect of Improving Systolic Blood Pressure and Low-density Lipoprotein Cholesterol Compared to Conventional Treatments and the Convenience of Taking Medication of Olostar Tab. in Patients With Essential Hypertension and Dyslipidemia.

The purpose of this study is to evaluate the effectiveness of Olostar Tablet on blood pressure and lipid profiles, obtain safety-related information for subgroups that failed to participate in the clinical trials, and to evaluate variables that affect treatment effectiveness.

开始日期2022-06-20

申办/合作机构

Daewoong Pharmaceutical Co., Ltd.

NCT05660135 / Active, not recruitingN/A

Reduction Efficacy of OLOMAX for Blood Pressure and Low-density Lipoprotein Cholesterol in Hypertensive Patients With Dyslipidemia: a Multi-center-database Real-world Study

This study is a large-scale, prospective, multi-center, and non-interventional observation study to observe blood pressure and blood lipid changes and safety during administration of olomax tablets for 24 weeks in hypertensive patients with dyslipidemia.

开始日期2022-06-20

申办/合作机构

Daewoong Pharmaceutical Co., Ltd.

NCT05259020 / Unknown status临床1期

An Open-label, Randomized, Single-dose, 2-sequence, 2-period, Cross-over, Clinical Trial to Evaluate the Pharmacokinetics and the Safety of ID14009 Compared to Coadministration of ID1805 With ID1803 in Healthy Adult Volunteers.

To evaluate the pharmacokinetics and the safety of ID14009 compared to coadministration of ID1805 with ID1803 in healthy adult volunteers.

开始日期2022-02-22

申办/合作机构

Ildong Pharmaceutical Co., Ltd.

100 项与 HMG-CoA reductase x AT1R 相关的临床结果

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100 项与 HMG-CoA reductase x AT1R 相关的转化医学

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0 项与 HMG-CoA reductase x AT1R 相关的专利（医药）

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项与 HMG-CoA reductase x AT1R 相关的文献（医药）

2008-12-01·Pharmacogenetics and Genomics4区 · 医学

Pharmacological effects of lipid-lowering drugs recapitulate with a larger amplitude the phenotypic effects of common variants within their target genes

4区 · 医学

Article

作者: Walker, Max C. ; Matthews, Paul M. ; Vollenweider, Peter ; Townsend, Ray ; Waterworth, Dawn M. ; Knouff, Christopher W. ; Song, Kijoung ; Yuan, Xin ; Waeber, Gerard ; Mooser, Vincent ; Lim, Noha

BACKGROUNDA major expectation underlying the search for novel susceptibility genes for common diseases using genome-wide association studies (GWAS) is that these discoveries will lead to new drug targets. This claim has not been verified yet. Here, we tested the hypothesis that common single nucleotide polymorphisms (SNPs) within drug target genes are associated with the corresponding phenotypes, using a population-based GWAS dataset and lipid-lowering drugs as a test case.METHODSWe examined the association between 36 genotyped and 193 imputed SNPs within four lipid-lowering drug target genes (HMGCR, PPARA, HM74A/GPR109A and CETP) and four non-lipid drug target genes (ACE, AGTR1, P2RY12, and ATP4B) and lipid phenotypes, blood pressure, and coronary artery disease in 5635 adult participants of the Lausanne, Switzerland, CoLaus study, genotyped using the Affymetrix 500K SNP chip technology.RESULTSThe phenotypes associated with SNPs within drug target genes recapitulated to a certain extent the pharmacological effects of the drug. The amplitude of the SNP effect was about 10 times smaller than the pharmacological effect of the corresponding drug. In particular, several CETP SNPs were associated with an elevation in HDL-cholesterol levels, yet a lower diastolic blood pressure, providing evidence that the blood pressure elevation induced by the CETP inhibitor torcetrapib is more likely compound specific than class specific.CONCLUSIONPharmacological modulation of lipid-lowering drug targets recapitulates, and markedly amplifies, the phenotypic effects of common SNPs within these target genes. This data provides indirect evidence that, with certain limitations, large-scale GWAS represent a new tool for the discovery and the development of innovative drugs.

2002-06-01·Journal of Hypertension2区 · 医学

A gene expression analysis in rat kidney following high and low salt intake

2区 · 医学

Article

作者: Dechend, Ralf ; Luft, Friedrich C. ; Gorzelniak, Kerstin ; Maass, Philipp G. ; Monti, Jan ; Sharma, Arya M. ; Barta, Peter ; Hubner, Norbert ; Muller, Dominik N.

BACKGROUNDThe effects of salt intake on renal regulation have been investigated for decades. To find new pathways and to demonstrate the utility of oligonucleotide expression arrays, we studied whole kidneys.METHODSEight Sprague-Dawley rats were divided into two groups. One group received a 6% salt (by weight) diet, while the other group received a 0.3%, otherwise identical, salt diet for 7 days. The rats were sacrificed after 7 days and the left kidney was subjected to RNA extraction. Oligonucleotide expression arrays (Affymetrix) were used to determine downregulation and upregulation, comparing high with low salt intake. Four rats from each group were studied separately.RESULTSThe experiments were reproducible. Thirty genes were downregulated with the high-salt diet, while 35 genes were upregulated. The renin gene, beta-2 glycoprotein-1, retinol binding protein, annexin VI, and the PTP2C protein tyrosine phosphatase were among the downregulated genes. The angiotensin II receptor type 1B receptor, HMG-CoA reductase, B7 antigen, and the rat calcium channel beta subunit III were among the upregulated genes. Differentially regulated were the p55 subunit (upregulated) and the p50 subunit (downregulated) of the phosphatidyl inositol 3-kinase enzyme complex. We verified our results by selecting a high-salt downregulated gene (renin) and an upregulated gene (B7 antigen) and subjecting these genes to real-time polymerase chain reaction. The results were consistent.CONCLUSIONOligonucleotide expression arrays can detect novel genes encoding for proteins not generally associated with responses to varied salt intake. Experiments of this nature have substantial limitations and require detailed verification. However, overall, the utility is promising.

2001-11-01·American Journal of Hypertension3区 · 医学

Modulating angiotensin II-induced inflammation by HMG Co-A reductase inhibition

3区 · 医学

Review

作者: Hilmar Bischoff ; Anette Fiebler ; Hermann Haller ; Ralf Dechend ; Carsten Lindschau ; Dominik Müller ; Rainer Dietz ; Friedrich C Luft ; Joon-Keun Park

Angiotensin (Ang) II is capable of producing inflammatory changes by signals through its AT1 receptor. Reactive oxygen species production, adhesion molecule expression, chemokines, and other mediators are involved. Nuclear factor-kappaB (NK-kappaB) and activator protein 1 (AP-1) are two of the transcription factors activating the responsible genes. We have studied Ang II-independent modulating effects in a double transgenic rat model harboring the human renin and angiotensinogen genes. We have recently focused on the protective effects of HMG-CoA reductase inhibition and review these data here. We found that cerivastatin decreased mortality, lowered blood pressure, preserved renal function, decreased cardiac hypertrophy, and inhibited the entire chain of inflammatory events. Furthermore, NF-kappaB and AP-1 activation was sharply attenuated. We also observed that cerivastatin blocked ERK1/2 phosphorylation in vivo and in vitro. Cerivastatin also inhibited phorbol ester-transmitted events in vascular smooth muscle cells. Because Rho, a member of the Ras protein superfamily is important to Ang II-dependent and -independent vascular smooth muscle signaling events, we suggest that cerivastatin may act by inhibiting the prenylation, membrane anchoring, and subsequent activation of Ras proteins. These data may in part explain cholesterol-independent, HMG-CoA reductase-related, protective effects.

项与 HMG-CoA reductase x AT1R 相关的新闻（医药）

2023-09-02

·智慧芽新药科讯

热门靶点 PCSK9 的高血脂代谢疾病市场竞争将杀成一片红海？

‍最新资讯8月28日，信达生物制药集团 (信达生物) 官网发布公告称，抗PCSK9单克隆抗体信必乐®（托莱西单抗注射液）在获得国家药品监督管理局（NMPA）批准后，8月25日开始正式正式向全国各大医院和药房供药，并迅速在北京大学第一医院，复旦大学附属中山医院等医院开出了全国首批处方。 “PCSK9抑制剂作为一种新型降胆固醇药物，能强效降低LDL-C水平且安全性良好。托莱西单抗在多个注册III期研究中展现出强大的降脂疗效和良好的安全性，与国内已上市PCSK9单抗相比，具有更长的给药间隔。尽管目前临床上已有多种降脂药物，但中国患者血脂整体达标情况不佳，相信托莱西单抗的上市会提升PCSK9单抗在降脂治疗方面的可及性，为广大高胆固醇血症及混合型血脂异常患者提供优质的治疗选择。” 北京大学第一医院霍勇教授表示：引此前8月中旬消息，信达生物的托莱西单抗注射液获得国家药品监督管理局（NMPA）批准，用于治疗原发性高胆固醇血症（包括杂合子型家族性和非家族性高胆固醇血症）和混合型血脂异常的成人患者。作为中国首个获批的本土自主研发PCSK9抑制剂，托莱西单抗注射液是信达生物布局心血管疾病领域的首款产品，也是信达生物成立12年来的第十款产品。 “与其他已获批的PCSK9单抗相比，托莱西单抗有更长给药间隔的优势，同时观察到脂蛋白a的明显下降。作为国内首个具有本土自主知识产权的PCSK9单抗，托莱西单抗的临床开发凝聚了国内多位心血管领域专家的心血，也证明了信达生物在心血管药物开发和临床开发领域的实力，以及监管机构对其疗效和安全性的认可。托莱西单抗的获批标志着信达生物在心血管及代谢（CVM）领域的前瞻布局开始进入收获期，信达生物将秉持着‘开发出老百姓用得起的高质量生物药’的使命，将为更广阔的慢病患者提供更多更优的治疗选择。” 信达生物制药集团临床开发副总裁钱镭博士表示：高胆固醇血症高胆固醇血症(hypercholesterolemia)，是指血液中胆固醇水平异常升高的一种状况。胆固醇是一种脂质类物质，它在人体中扮演着重要的角色，包括细胞膜的构建、激素合成和胆汁酸的产生等。当血液中的胆固醇水平持续升高时，可能会增加心血管疾病（如冠心病、中风及动脉粥样硬化等）的风险。由于胆固醇不溶于水，它在血浆中通过脂蛋白颗粒运输。脂蛋白按密度分为：极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）、中密度脂蛋白（IDL）、和高密度脂蛋白（HDL）。所有脂蛋白都携带胆固醇，较高水平的高密度脂蛋白胆固醇具有保护作用，而低密度脂蛋白胆固醇水平升高与动脉粥样硬化和冠心病风险增加有关。根据此前文章推介，重磅解读：IQVIA 发布全球肥胖浪潮下心血管代谢创新药的复兴，IQVIA 发布的代谢性疾病相关市场调研，高水平低密度脂蛋白胆固醇 (LDL-C) 已经成为全球范围内死亡率和发病率的主要风险因素之一。在正常情况下，位于肝细胞表面的低密度脂蛋白受体(LDLR) 与 APOB/LDL-C 结合形成复合物，并通过 LDLR 与 LDLRAP1 的相互作用，复合物被内吞进入细胞。当复合物在细胞内解离时，LDLR 通常会回收到细胞质膜，游离胆固醇则会在细胞内消耗掉。PCSK9 通过细胞表面的相互作用介导 LDLR 的活性抑制。来源于，DOI: 10.3389/fgene.2020.572045在遗传性高胆固醇血症中，LDLR、APOB、PCSK9 和 LDLRAP1 的单个突变可导致从轻微到严重的多种表型。LDLR 突变会影响 LDL-C 与 LDLR 的结合，导致 LDL-C 在血液循环中蓄积。APOB 基因突变会导致蛋白质功能障碍，使 LDL-C 与 LDLR 的结合受到限制。PCSK9 基因突变可导致：(1) PCSK9 活性增加；(2) 没有 LDLR 循环；(3) 血浆中 LDL-C 水平累积。在这种情况下，抗 PCSK9 疗法，包括新出现的 PCSK9 抑制剂（如 alirocumab、evolocumab），可用于降低 LDL-C，预防心血管疾病。高胆固醇血症相关药研现状根据智慧芽新药情报中心统计，高胆固醇血症及其相关的代谢性疾病是全球药企的热门研究适应症，共有337个高胆固醇血症药物，来自311个机构，覆盖71个靶点，开展1872个临床试验。在适应症高胆固醇血症下，HMG-CoA reductase 是最常见的临床靶点，有7个药物已经获得批准上市，还有20个药物处于非在研阶段。其次是PCSK9靶点，有4个药物获得批准上市，13个药物处于临床前阶段，21个药物处于非在研阶段。以靶向 PCSK9 的药物为例，包括开篇提到的信达生物的托莱西单抗 (Tafolecimab)、Novartis的英克司兰钠 (Inclisiran)、Sanofi 和 Regeneron 的阿利西尤单抗 (Alirocumab) 以及安进公司的依洛尤单抗 (Evolocumab) 均已获批上市用于高胆固醇血症或血脂障碍等相关疾病。另有多款药物处于申请上市阶段。在GPCR 类靶点方面，热门靶点包括NIACR1、AT1R、HCAR3、LTRs、PGD2R、GPR120等，成为治疗高胆固醇血症的临床治疗靶点。其中，NIACR1 激动剂 Acipimox、H1/H3 受体双重拮抗剂 Betahistine、HCAR3/NIACR1 双重激动剂 Niacin 均已获批上市用于治疗高胆固醇血症、动脉粥样硬化、脂质代谢紊乱等相关疾病。诺华公司的小干扰核酸药物: Inclisiran8月22日，诺华公司 (Novartis）的英克司兰钠宣布其长效降脂小干扰核酸（siRNA）降胆固醇药物英克司兰钠（Inclisiran）注射液获得中国国家药监局批准，用于成人原发性高胆固醇血症或混合性血脂异常患者的治疗。据悉，Inclisiran是目前全球首款也是唯一一款用于降低低密度脂蛋白胆固醇（LDL-C）的siRNA疗法，患者每年进行两次注射即可降低LDL-C。由于这款药物的长效性，患者无需每天服药，因此inclisiran也被称为心血管领域的“疫苗”。8月28日，诺华官网再次重磅公布 ORION-8 的最新长期数据，ORION-8 是 ORION-9、ORION-10、ORION-11 和 ORION-3 试验的 III 期开放标签扩展试验。这些数据表明，Leqvio (Inclisiran) 在他汀类药物治疗的基础上，通过每年两次给药，可在动脉粥样硬化性心血管疾病 (ASCVD) 或杂合性家族性高胆固醇血症 (HeFH)1 患者中持续降低低密度脂蛋白胆固醇 (LDL-C)，并可持续六年以上。Merck 公司的口服PCSK9 抑制剂: MK-06168月25日，默克公司 (Merck) 官网发布公告称，正式启动公司的一项3期临床项目CORALreef。该项目旨在研究MK-0616，一款正在研究的口服 PCSK9 抑制剂，用于治疗成人高胆固醇血症。据悉，这是首个口服 PCSK9 抑制剂的 3 期临床项目。目前，首批参与者正在参加两项评估 MK-0616 降低低密度脂蛋白（LDL-C) 的注册 3 期研究：CORALreef Lipids 和 CORALreef HeFH。默克还计划在2023年底前启动一项3期心血管结果研究--CORALreef Outcomes。下图为 www.clinicaltrials.gov 上关于 MK-0616 的临床研究情况: 以上文章来源于GPCR drug diacovery，作者段思研‍ 本文仅作信息交流之目的，文中观点不代表相关疾病治疗立场，也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

上市批准申请上市临床3期

2023-05-28

·医药地理

2022年获批进口药品分析（心血管系统用药、神经系统用药）

本文数据来自于CPM新药研发监测数据库（cpm.pharmadl.com）。心血管系统用药2022年NMPA批准的进口心血管系统用药，共计71个（按照注册证号分类），获批品种数量前五的几家企业分别为拜耳（12个）、赛诺菲（8个）、勃林格殷格翰（7个）、Kyowa Kirin（6个）、Organon Pharma（6个）；涉及靶点排名前三的是AGTR1（20个）、CACNA1C（14个）、Hmgcr（14个）。在政策相关度方面，2022年获批的进口心血管系统用药中，2022国家医保目录品种共有67个，没有带量采购招标品种。神经系统用药2022年NMPA批准的进口神经系统用药，共计55个（按照注册证号分类），获批品种前三的企业分别是Napp Pharmaceuticals（8个）、Dr Reddy's Laboratories（6个）、Mundipharma Research（6个）；涉及靶点排名前三的是Nav1.1（9个）、ACHE（7个）、OPRK1（6个）。在政策相关度方面，2022年获批的进口神经系统用药中，2022国家医保目录品种共有49个，没有带量采购招标品种。年度发布2023年《全球药研新动态》《中国医院市场用药格局》（2023版）2023年《数图药讯》权威发布2021年度中国医药工业百强榜单解读中国仿制药发展报告（2022版）医药行业专项报告中国医药中间体和原料药行业调研报告中国非甾体抗炎类原料药市场调研报告中国祛痰类原料药市场调研报告中国钙拮抗剂类原料药市场调研报告中国血管紧张素Ⅱ受体拮抗剂类原料药市场调研报告中国口服血糖调节类原料药市场调研报告中国中枢兴奋类原料药市场调研报告中国抗痛风类原料药市场调研报告中国脑血管病类原料药市场调研报告END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

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