anacetrapib (MK-0859) / Merck (MSD) 
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  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Preclinical, Journal:  CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice. (Pubmed Central) -  Apr 29, 2024   
    Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice...In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.
  • ||||||||||  obicetrapib (TA-8995) / NewAmsterdam Pharma, Menarini, anacetrapib (MK-0859) / Merck (MSD)
    Journal:  The Evolving Role of Cholesteryl Ester Transfer Protein Inhibition Beyond Cardiovascular Disease. (Pubmed Central) -  Nov 27, 2023   
    In fact, certain HDL subclasses may, in contrast, be beneficial for treating the retinal cholesterol accumulation that occurs with AMD. This review describes the latest biological evidence regarding the relationship between HDL and CETP inhibition for Alzheimer's disease, type 2 diabetes mellitus, sepsis, and AMD.
  • ||||||||||  Review, Journal:  Structure-based mechanism and inhibition of cholesteryl ester transfer protein. (Pubmed Central) -  Mar 24, 2023   
    Insights into the structural-based CETP-lipoprotein interactions can unravel CETP inhibition machinery, which can hopefully guide the design of more effective CETP inhibitors that combat ASCVD. Individual-molecule 3D structures of CETP bound to lipoproteins provide a model for understanding the mechanism by which CETP mediates lipid transfer and which in turn, guide the rational design of new anti-ASCVD therapeutics.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Journal:  Alternaria alternata Causing Brown Spot Disease on Walnut in Xinjiang, China. (Pubmed Central) -  Jan 7, 2023   
    ITS, endoPG and H3 sequences had 99.81% (1/535 nt difference), 99.78% (1/448 nt difference) and 100% (0/417 nt difference) homology with homologous sequences of A. alternata strains (KP124306 [ITS], KP124006 [endoPG], MK085979 [H3]), respectively...Forest Research. 30(6):1004-1008.
  • ||||||||||  dalcetrapib (JTT-705) / DalCor, anacetrapib (MK-0859) / Merck (MSD)
    Preclinical, Journal:  Dalcetrapib and anacetrapib increase apolipoprotein E-containing HDL in rabbits and humans. (Pubmed Central) -  Nov 22, 2022   
    Overall, in rabbits and humans, CETPi increase large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport.
  • ||||||||||  Journal:  CETP-inhibitors: from HDL-C to LDL-C lowering agents? (Pubmed Central) -  Nov 15, 2022   
    Although first-generation CETP inhibitors (torcetrapib, dalcetrapib) were mainly raising HDL-C or had off-target effects, next generation CETP inhibitors (anacetrapib, evacetrapib) were also effective in reducing LDL-C and apoB and have been proven safe...The newest-generation CETP inhibitor obicetrapib, specifically designed to lower LDL-C and apoB, has achieved significant reductions of LDL-C up to 45%. Obicetrapib, about to enter phase III development, could become the first CETP inhibitor as add-on therapy for patients not reaching their guideline LDL-C targets.
  • ||||||||||  obicetrapib (TA-8995) / NewAmsterdam Pharma, Menarini, anacetrapib (MK-0859) / Merck (MSD)
    Review, Journal, Adverse events:  Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels. (Pubmed Central) -  Sep 3, 2022   
    An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Clinical, Journal:  Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease. (Pubmed Central) -  Apr 9, 2022   
    P3
    The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Clinical, Journal:  Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population. (Pubmed Central) -  Feb 25, 2022   
    The study first tested whether a CETP allele score was associated with morbidity and mortality, when scaled to genetically lower levels of non-high-density lipoprotein (HDL) cholesterol (ie, 17 mg/dL), corresponding to the reduction observed for anacetrapib vs placebo in the Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial...Per 1 million person-years, the projected 1916 more AMD events associated with genetically higher levels of HDL cholesterol was similar to the 1962 fewer events of cardiovascular mortality and myocardial infarction combined associated with genetically lower levels of non-HDL cholesterol. This study suggests that genetic CETP deficiency, mimicking pharmacologic CETP inhibition, was associated with a lower risk of cardiovascular morbidity and mortality, but with a markedly higher risk of AMD.
  • ||||||||||  obicetrapib (TA-8995) / NewAmsterdam Pharma, anacetrapib (MK-0859) / Merck (MSD)
    Review, Journal:  Pathophysiology and inhibition of cholesteryl ester transfer protein for prevention of cardiovascular diseases: an update. (Pubmed Central) -  Jan 18, 2022   
    When the CETP concentration is decreased by CETP inhibitors (e.g., anacetrapib, torcetrapib, obicetrapib, etc.), high-density lipoprotein (HDL) particles are formed and low-density lipoprotein (LDL) is decreased along with cholesterol transportation alteration, which reduces the development of atherosclerosis. Here, we discuss the role of CETP inhibitors in reducing well-known 'bad' cholesterols and the current status of trials of different CETP inhibitors, their adverse effects, and limitations, as well as the pathophysiology of CETP.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Journal:  Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis. (Pubmed Central) -  Jan 4, 2022   
    APOE*3-Leiden.CETP mice treated with anacetrapib had preserved levels of HDL-C and apolipoprotein-AI and increased survival relative to placebo treatment (70.6% vs 35.3%, Log-rank p=0.03), while there was no effect of anacetrapib on the survival of APOE*3-Leiden mice which do not express CETP (50.0% vs 42.9%, Log-rank p=0.87). Clinical genetics and humanized mouse models suggest that inhibiting CETP may preserve HDL levels and improve outcomes for individuals with sepsis.
  • ||||||||||  obicetrapib (TA-8995) / Mitsubishi Tanabe, Amgen
    [VIRTUAL] Obicetrapib Lowers LDL-C in Patients Taking High Intensity Statins: Results From Rose Clinical Trial (Live) -  Nov 9, 2021 - Abstract #AHA2021AHA_7418;    
    This was confirmed in REVEAL; by lowering LDL-C, anacetrapib was associated with a reduction in cardiovascular events. Obicetrapib at doses of 5 and 10 mg produced robust decreases in LDL-C, ApoB and Non-HDL-C and increases in HDL-C compared to placebo in patients treated with high intensity statins and was safe and well tolerated.
  • ||||||||||  Parmodia (pemafibrate) / Kowa, Livalo (pitavastatin) / Kowa, Eli Lilly
    Journal:  Recent advances in synthetic pharmacotherapies for dyslipidaemias. (Pubmed Central) -  Oct 3, 2021   
    Probucol stimulates reverse cholesteryl ester transport, lowers LDL-C stabilizing plaques and may lower incidence of cardiovascular events. These agents, which act through novel mechanisms, afford good and potentially safe treatment choices that may increase adherence and the attainment of therapeutic targets.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    [VIRTUAL] Impact of adverse events on quality of life and hospital costs in secondary cardiovascular disease prevention () -  Jul 6, 2021 - Abstract #ESC2021ESC_4628;    
    We estimate QoL and annual hospital costs associated with a range of adverse events of interests using the individual participant data from the Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification (REVEAL) trial...The QoL model (Figure 2) indicated large QoL decrements associated with non-fatal non-haemorrhagic stroke, heart failure hospitalization, incident cancer and non-coronary revascularization, and comparatively small QoL decrement associated with experiencing non-fatal myocardial infarction. Conclusion These cost and QoL models in a well-managed contemporary high CVD risk patient population would assist in assessments of long-term net effects and cost-effectiveness of novel interventions to reduce cardiovascular risk.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, dalcetrapib (JTT-705) / DalCor, anacetrapib (MK-0859) / Merck (MSD)
    Review, Journal:  Cholesteryl ester transfer protein inhibitors in precision medicine. (Pubmed Central) -  Jun 22, 2021   
    Although REVEAL trail has recently shown that Anacetrapib could reduce major coronary events, it was also shown to induce excessive lipid accumulation in adipose tissue; thereby, the further regulatory approval will not be sought...In the present review, we summarize the current understanding of the functions of CETP and the outcomes of the phase III randomized controlled trials of CETP inhibitors. In addition, we also put forward the implications from results of the trials which potentially suggest that the CETP inhibitors could be a promising precise therapeutic medicine for CVD based on genetic background.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Journal:  Effect of Anacetrapib on Cholesterol Efflux Capacity: A Substudy of the DEFINE Trial. (Pubmed Central) -  Mar 16, 2021   
    Among patients with diabetes mellitus, anacetrapib increased CEC in those with the normal 1-1 haptoglobin genotype (standard β, 0.42; 95% CI, 0.16-0.69) but not the dysfunctional 2-1/2-2 genotypes (P interaction=0.02). Conclusions Among patients with CHD, anacetrapib at a dose linked to improved CHD outcomes significantly increased CEC independent of changes in high-density lipoprotein cholesterol or other lipids, with effect modification by sex and a novel pharmacogenomic interaction by haptoglobin genotype, suggesting a putative mechanism for reduced risk requiring validation.
  • ||||||||||  Xtandi (enzalutamide) / Pfizer, Astellas, anacetrapib (MK-0859) / Merck (MSD), Spherazole (itraconazole) / RA Chem, JW Pharma, Spherics
    Journal:  A practical approach to modeling the impact of amorphous drug nanoparticles on the oral absorption of poorly soluble drugs. (Pubmed Central) -  Nov 19, 2020   
    The results show good agreement using the nano-modified permeability, which described the data better than the standard baseline predictions. The nano-modified permeability method can be a suitable, fit-for-purpose in silico approach for evaluating or predicting oral absorption of poorly soluble, UWL-limited drugs from formulations that produce a significant number of amorphous drug nanoparticles.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Journal:  The Cholesteryl Ester Transfer Protein Inhibitor, des-Fluoro-Anacetrapib, Prevents Vein Bypass-induced Neointimal Hyperplasia in New Zealand White Rabbits. (Pubmed Central) -  Oct 30, 2020   
    Des-fluoro-anacetrapib treatment was also associated with decreased bypass grafting-induced endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), endothelial dysfunction, and smooth muscle cell (SMC) proliferation in the grafted vein. In conclusion, increasing HDL-C levels by inhibiting CETP activity is associated with inhibition of intimal hyperplasia in grafted veins, reduced inflammatory responses, improved endothelial function, and decreased SMC proliferation.