Review
Cardiac & Cardiovascular Systems
Nick S. Nurmohamed, Marc Ditmarsch, John J. P. Kastelein
Summary: Cholesteryl ester transfer protein (CETP) is a liver-synthesized glycoprotein that facilitates the transfer of cholesterol esters and triglycerides between different lipoprotein particles. Recent studies have shown that the benefit of CETP inhibitors in atherosclerotic cardiovascular disease (ASCVD) is primarily due to the reduction of LDL-C and apoB, rather than an increase in HDL-C. Genetic evidence supports the use of CETP inhibitors, as they achieve similar reductions in ASCVD risk as other lipid-lowering medications. The newest generation of CETP inhibitors not only lower LDL-C, but also reduce the risk of new-onset diabetes and improve glucose tolerance and insulin sensitivity.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yizhen Zhao, Dongxiao Hao, Yifan Zhao, Shengli Zhang, Lei Zhang, Zhiwei Yang
Summary: This study compared the structural characteristics of authentic CETP and mutant CETP through molecular dynamics simulations, revealing that authentic CETP exhibits greater flexibility and curvature in lipid transport. A ligand identified through virtual screening and simulations was found to bind to the N- and C-termini of CETP, inducing structural changes unfavorable to lipid transport. This study sheds new light on the relationship between the structural and functional mechanisms of CETP and provides novel ideas for precise regulation of CETP functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Surojit Banerjee, Abhijit De
Summary: This article discusses the role of CETP inhibitors in reducing 'bad' cholesterol and preventing cardiovascular disease, including the current status of trials with different drugs, their adverse effects and limitations, as well as the pathophysiology of CETP.
DRUG DISCOVERY TODAY
(2021)
Review
Cell Biology
Shinji Yokoyama
Summary: Schistosomiasis is a life-threatening parasitic disease caused by blood flukes. The parasites obtain nutrients from the host via their body surface and alimentary tracts. CD36-related protein in Asian blood fluke plays a crucial role in the uptake of cholesteryl ester, and deficiency in cholesteryl ester transfer protein resists pathogenic growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Dongxiao Hao, He Wang, Yongjian Zang, Lei Zhang, Zhiwei Yang, Shengli Zhang
Summary: This study provides valuable insights into the mechanism of glycosylation in modulating CETP and its potential implications for cardiovascular disease treatment and functional studies in other systems.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Hematology
Jeremy D. Furtado, Giacomo Ruotolo, Stephen J. Nicholls, Robert Dullea, Santos Carvajal-Gonzalez, Frank M. Sacks
Summary: This study suggests that increasing HDL by inhibiting CETP does not reduce the risk of cardiovascular disease but instead increases the levels of dysfunctional HDL subspecies associated with higher risk.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Jian Liu, Patrick P. Shao, Deodial Guiadeen, Arto Krikorian, Wanying Sun, Qiaolin Deng, Anne-Marie Cumiskey, Ruth A. Duffy, Beth A. Murphy, Kaushik Mitra, Douglas G. Johns, Joseph L. Duffy, Petr Vachal
Summary: CETP inhibitors reduce cholesterol ester transfer between lipoproteins, increasing HDL-C levels and potentially reducing the risk of heart disease and stroke. CETP inhibitors based on cyclic, bicyclic urea, and sulfamide cores demonstrate potent in vitro activity and in vivo efficacy in increasing HDL-C levels.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Julia Nowowiejska, Anna Baran, Julita A. Krahel, Tomasz W. Kaminski, Magdalena Maciaszek, Iwona Flisiak
Summary: Psoriasis is associated with metabolic disorders, and this study found a correlation between psoriasis and cholesteryl ester transfer protein (CETP) and sortilin (SORT), which are involved in lipid metabolism. However, CETP and SORT cannot be used as individual biomarkers. CETP concentration may be investigated as a marker for liver side effects of acitretin treatment, while SORT could be considered as a new indicator of metabolically induced inflammation in psoriasis patients.
Article
Cardiac & Cardiovascular Systems
Hiroki Yuge, Hiroshi Okada, Masahide Hamaguchi, Kazushiro Kurogi, Hiroaki Murata, Masato Ito, Michiaki Fukui
Summary: The ratio of TG/HDL-C is strongly associated with the risk of developing type 2 diabetes, and it can be a better predictor than LDL-C, HDL-C, or TG alone.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Brian T. Palmisano, Uche Anozie, Sophia Yu, Joshua C. Neuman, Lin Zhu, Emery M. Edington, Thao Luu, John M. Stafford
Summary: Elevated postprandial triacylglycerols (TAG) are a significant risk factor for cardiovascular disease, with men having higher levels compared to women. The lipid shuttling protein cholesteryl ester transfer protein (CETP) plays a role in increasing plasma TAG in males, impairing TAG clearance, especially in very-low density lipoprotein (VLDL). Understanding the impact of CETP and androgen signaling on TAG metabolism in males may lead to novel approaches to reduce TAG levels and mitigate cardiovascular disease risk.
Article
Pediatrics
Florencia Ferraro, Maximiliano Martin, Julian Verona, Lisandro Gilligan, Maria Florencia Verona, Eliana Botta, Walter Tetzlaff, Ezequiel Lozano Chiappe, Laura Boero, Fernando Brites
Summary: Children and adolescents with TG/HDL-C >= 3.0 presented a more atherogenic lipid profile and higher CETP and Lp-PLA(2) activities, indicating potential alterations in lipoprotein metabolism and quality.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Review
Biochemistry & Molecular Biology
Adam J. Nelson, Allan D. Sniderman, Marc Ditmarsch, Mary R. Dicklin, Stephen J. Nicholls, Michael H. Davidson, John J. P. Kastelein
Summary: Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides between HDL particles and TG-rich, apoB-containing particles. Initially, CETP inhibitors were developed to raise plasma HDL-C levels to lower the risk of ASCVD. However, recent evidence suggests that CETP inhibitors can reduce LDL-C and apoB concentrations, thereby reducing the risk of major coronary events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Anna E. Bortnick, Petra Buzkova, James Otvos, Majken Jensen, Michael Y. Tsai, Matthew Budoff, Rachel Mackey, Samar R. El Khoudary, Elda Favari, Ryung S. Kim, Carlos J. Rodriguez, George Thanassoulis, Jorge R. Kizer
Summary: This study found that high-density lipoprotein (HDL) cholesterol, HDL particle number and size, apoC3-defined HDL subtypes were inversely associated with the long-term incidence and progression of aortic valve calcification (AVC). Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Mark Trinder, Yanan Wang, Christian M. Madsen, Tatjana Ponomarev, Lubos Bohunek, Brendan A. Daisely, HyeJin Julia Kong, Lisanne L. Blauw, Borge G. Nordestgaard, Anne Tybjaerg-Hansen, Mark M. Wurfel, James A. Russell, Keith R. Walley, Patrick C. N. Rensen, John H. Boyd, Liam R. Brunham
Summary: Clinical genetics and humanized mouse models suggest that inhibiting CETP may preserve high-density lipoprotein levels and improve outcomes for individuals with sepsis.
Article
Biochemistry & Molecular Biology
Jun Chen, Haihua Qi, Lijun Liu, Yandong Niu, Shuping Yu, Shucun Qin, Lei He
Summary: Elevated CETP and PLTP levels were found to worsen psoriasis symptoms in a mouse model, leading to increased expression of inflammatory cytokines.
LIPIDS IN HEALTH AND DISEASE
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)