更新于：2024-11-01

NPC1L1 x CETP

更新于：2024-11-01

基本信息

关联

项与 NPC1L1 x CETP 相关的药物

Obicetrapib/Ezetimibe

靶点

CETP x NPC1L1

作用机制

CETP抑制剂 [+1]

在研机构

NewAmsterdam Pharma Holding BV

原研机构

NewAmsterdam Pharma Co. NV

在研适应症

动脉粥样硬化斑块

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

项与 NPC1L1 x CETP 相关的临床试验

NCT06005597 / Active, not recruiting临床3期

A Placebo-Controlled, Double-Blind, Randomized, Phase 3 Study to Evaluate the Effect of Obicetrapib 10 mg and Ezetimibe 10 mg Fixed Dose Combination Daily on Top of Maximally Tolerated Lipid-Modifying Therapy in Participants With Heterozygous Familial Hypercholesterolemia (HeFH) and/or Atherosclerotic Cardiovascular Disease (ASCVD) or Multiple ASCVD Risk Factors

The study is a placebo-controlled, double-blind, randomized, phase 3 study in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors to evaluate the efficacy, safety and tolerability of obicetrapib 10mg and ezetimibe 10mg fixed dose combination as an adjunct to diet and maximally tolerated lipid-lowering therapy.

开始日期2024-03-01

申办/合作机构

NewAmsterdam Pharma Co. NV

NCT06305559 / Not yet recruiting临床3期

A Placebo-controlled, Double-blind, Randomized, Phase 3 Study to Evaluate the Effect of Obicetrapib/Ezetimibe Fixed Dose Combination Daily on Coronary Plaque Characteristics in Participants With Atherosclerotic Cardiovascular Disease on Coronary CT Angiography (REMBRANDT Trial)

This placebo-controlled, double-blind, randomized, Phase 3 study is being conducted in adult participants with high-risk atherosclerotic cardiovascular disease (ASCVD) who are not adequately controlled by their maximally tolerated lipid-modifying therapy, to assess the impact of the obicetrapib 10 mg + ezetimibe 10 mg FDC daily on coronary plaque and inflammation characteristics, evaluated using cardiovascular computed tomography angiography (CCTA).

开始日期2024-03-01

申办/合作机构

NewAmsterdam Pharma Holding BV

100 项与 NPC1L1 x CETP 相关的临床结果

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100 项与 NPC1L1 x CETP 相关的转化医学

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0 项与 NPC1L1 x CETP 相关的专利（医药）

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项与 NPC1L1 x CETP 相关的文献（医药）

2024-07-23·European Journal of Preventive Cardiology

Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study

Article

作者: Chen, Siyu ; Chen, Jiejian ; Zhang, Xinlu ; Liao, Yulin ; Liang, Hongbin ; Zhang, Qiuxia ; Xiao, Min ; Luo, Wei ; Qu, Liyuan ; Lei, Li ; Xiu, Jiancheng ; Yan, Shaohua ; Zhou, Zhongjiang ; Gao, Xiong ; Lee, Alex Pui-Wai ; Yang, Miaomiao ; Wang, Yuegang

AbstractAimsThe lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA.Methods and resultsOur research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20–2.09, P = 1.20 × 10−03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13–1.46, P = 1.48 × 10−04; aortic minimum area: OR = 1.26, 95% CI = 1.21–1.42, P = 1.78 × 10−04). PCSK9 (proprotein convertase subtilisin/kexin type 9) and CETP (cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10–1.63, P = 3.07 × 10−03; CETP: OR = 1.38, 95% CI = 1.06–1.80, P = 1.47 × 10−02). No evidence to support genetically mediated NPC1L1 (Niemann–Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA.ConclusionThis study provides causal evidence for the genetic association between lipid-lowering drugs and AA. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

2024-07-01·European Journal of Pain

Mendelian randomization study of lipid metabolism characteristics and migraine risk

Article

作者: Hong, Peiwei ; Han, Lin ; Wan, Yang

AbstractBackgroundThe association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk.MethodsSingle‐nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid‐lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome‐wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid‐lowering drugs with migraine risk.ResultsRegarding serum lipids, it was found that SNPs related to high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL‐C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL‐C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL‐C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000).ConclusionsThere is a relationship between lipid metabolism characteristics and migraine risk.SignificanceBased on the genome‐wide association summary data, single‐nucleotide polymorphisms (SNPs) related to high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL‐C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL‐C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.

2024-06-01·Cancer Causes & Control

Circulating lipids, lipid-lowering drug targets, and breast cancer risk: Comprehensive evidence from Mendelian randomization and summary data-based Mendelian randomization

Article

作者: Zhang, Zhongxu ; Zhang, Daxin

BACKGROUNDBreast cancer (BC) is the most common and fatal cancer among women, yet the causal relationship between circulating lipids, lipid-lowering drugs, and BC remains unclear.METHODSMendelian randomization (MR) and summary data-based MR (SMR) analysis are used to explore the causal relationship between plasma lipids, lipid-lowering drug targets, and BC.RESULTSThe result of MR suggested that per mg/dL higher levels of LDL-C (OR = 1.045, FDR = 0.023), HDL-C (OR = 1.079, FDR = 0.003), TC (OR = 1.043, FDR = 0.026), and APOA-I (OR = 1.085, FDR = 2.64E-04) were associated with increased BC risk, while TG was associated with reduced BC risk (OR = 0.926, FDR = 0.003). Per mg/dL higher levels of HDL-C (OR = 1.080, FDR = 0.011) and APOA-I (OR = 1.083, FDR = 0.002) were associated with increased ER+BC risk, while TG was associated with reduced ER+BC risk (OR = 0.909, FDR = 0.002). For every per 1 mg/dL decrease in LDL, HMGCR (OR: 0.839; FDR = 0.016), NPC1L1 (OR: 0.702; FDR = 0.004), and PCSK9 (OR: 0.916; FDR = 0.026) inhibition were associated with reduced BC risk, whereas CETP inhibition (OR: 1.194; FDR = 0.026) was associated with increased BC risk. For every per 1 mg/dL decrease in LDL, HMGCR (OR: 0.822; FDR = 0.023), NPC1L1 (OR: 0.633; FDR = 2.37E-03), and APOB inhibition (OR: 0.816; FDR = 1.98E-03) were associated with decreased ER-BC risk, while CETP inhibition (OR: 1.465; FDR = 0.011) was associated with increased ER-BC risk. SMR analysis indicated that HMGCR was associated with increased BC risk (OR: 1.112; p = 0.044).CONCLUSIONLipids are associated with the BC risk, and lipid-lowering drugs targets HMGCR, NPC1L1, PCSK9, and APOB may be effective strategies for preventing BC. However, lipid-lowering drugs target CETP may potentially increase BC risk.