Review
Endocrinology & Metabolism
Deng Pan, Lin Xu, Ming Guo
Summary: Protein kinase C (PKC) plays a crucial role in the development of diabetic microvascular complications by becoming activated under high-glucose conditions, leading to the accumulation of redox stress. This activation affects various types of cells in the microvasculature, resulting in changes in blood flow, microvascular permeability, extracellular matrix accumulation, basement thickening, and angiogenesis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Jessy Chen, Thomas Fleming, Sylvia Katz, Matthias Dewenter, Kai Hofmann, Alireza Saadatmand, Mariya Kronlage, Moritz P. Werner, Bianca Pokrandt, Friederike Schreiter, Jihong Lin, Daniel Katz, Jakob Morgenstern, Ahmed Elwakiel, Peter Sinn, Hermann-Josef Groene, Hans-Peter Hammes, Peter P. Nawroth, Berend Isermann, Carsten Sticht, Britta Bruegger, Hugo A. Katus, Marco Hagenmueller, Johannes Backs
Summary: This study investigated the role of CaMKII δ in diabetes and found that diabetic mice lacking CaMKII δ did not develop hyperglycemia, but still exhibited diabetic nephropathy while diabetic retinopathy was prevented. This challenges the clinical concept of normalizing hyperglycemia in diabetes for late diabetic complications and emphasizes the need for detailed analysis of intracellular metabolic signals in different organs affected by diabetes.
Article
Pharmacology & Pharmacy
Yao Chen, Bernardo L. Sabatini
Summary: In addition to inhibiting PKA activity, PKI was found to facilitate the activation of multiple isoforms of PKC at higher concentrations. This suggests the need for appropriate interpretation of experimental results when using PKI as a pharmaceutical agent. The study provides a foundation for exploring the potential functions of PKI in regulating PKC activity and coordinating PKC and PKA activities.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Sona Krajcovicova, Radek Jorda, David Vanda, Miroslav Soural, Vladimir Krystof
Summary: An efficient synthetic approach for trisubstituted imidazo [4,5-c]pyridines as BTK inhibitors was reported, with high tolerance of C6 substitutions observed. Cellular experiments indicated selective BTK targeting, suggesting the inhibitors could be potential options after ibrutinib failure.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Immunology
Dan Ke, Zhen Zhang, Jieting Liu, Peijian Chen, Yucen Dai, Xinhai Sun, Yanhui Chu, Luxin Li
Summary: Diabetes is a metabolic disease that causes chronic high blood sugar, leading to harmful inflammation and complications. Anti-inflammatory drugs, specifically targeting RIPK1 and RIPK3, have shown potential in managing inflammation and treating diabetes complications. This review provides a summary of the current research on the mechanism of action and drug development of RIPK1 and RIPK3.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Daiki Hayashi, Yasuhito Shirai
Summary: The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients' quality of life and medical expenses. The activation of DGK to inhibit PKC activation shows potential therapeutic effect in ameliorating diabetic nephropathy.
Article
Multidisciplinary Sciences
Jun-Jun Yeh, I-Ling Kuo, Hei-Tung Yip, Min-Yuan Hsueh, Chung-Y Hsu, Chia-Hung Kao
Summary: This study aimed to investigate the impact of colchicine use on stroke risk in patients with diabetes mellitus. The results showed that colchicine use was associated with a lower incidence of stroke, particularly ischemic stroke, in patients with diabetes. However, there was no significant association between colchicine use and hemorrhagic stroke in patients with diabetes without gout.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Liding Zhao, Ya Li, Tian Xu, Qingbo Lv, Xukun Bi, Xianglan Liu, Guosheng Fu, Yunzeng Zou, Junbo Ge, Zhaoyang Chen, Wenbin Zhang
Summary: This study found that diabetes mellitus plays a significant role in aggravating chronic inflammation and promoting atherosclerosis, in conjunction with hyperlipidemia. The mechanism of action may involve the induction of immune maturation of dendritic cells, likely through the RAGE-TLR4-PKC β(1) signaling pathway.
MOLECULAR MEDICINE
(2022)
Editorial Material
Hematology
Jan A. Burger
Summary: The study reveals that MARCKS protein is differentially expressed in patients with chronic lymphocytic leukemia based on the mutation status of IGHV, and its expression and phosphorylation are linked to CLL cell migration through key signaling pathways. The findings were also confirmed in samples from patients treated with the BTK inhibitor acalabrutinib.
Article
Food Science & Technology
Ping Tang, Xinzhou Yang, Huijian Chen, Ting Zhang, Hui Tang, Kejian Pang
Summary: This study demonstrates the antidiabetic activity of ethyl acetate extract of Morus nigra L. twigs (MNT-EA) and its potential mechanisms through the activation of AMPK/PKC/GLUT4 signaling pathway, which enhances glucose uptake and improves diabetic symptoms.
JOURNAL OF FUNCTIONAL FOODS
(2022)
Article
Chemistry, Medicinal
Seungbeom Lee, Jisu Kim, Jeyun Jo, Jae Won Chang, Jaehoon Sim, Hwayoung Yun
Summary: Bivalent kinase inhibitors have emerged as a promising approach for targeting specific kinases with enhanced selectivity and affinity through increased interactions with target enzymes. Recent developments have led to the creation of bivalent compounds with high kinase affinity, biological and chemical stability in vivo, offering significant potential for therapeutic applications. This review provides a comprehensive overview of hetero-bivalent kinase inhibitors and discusses their advantages, limitations, and future prospects compared to monovalent kinase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Hao Xie, Xing-Yi Shen, Na Zhao, Peng Ye, Zhen Ge, Zuo-Ying Hu
Summary: In diabetic mice, ivabradine alleviates cardiac fibrosis and diastolic dysfunction by suppressing CF proliferation and activation, regulating the phosphorylation of JNK and p38 MAPK, and enhancing matrix metalloproteinase 2 expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Takahito Kawano, Junichi Inokuchi, Masatoshi Eto, Masaharu Murata, Jeong-Hun Kang
Summary: PKC is a family of important kinases classified into three subfamilies based on structural and activation characteristics, and used for understanding intracellular signaling pathways and treating related diseases. While PKC inhibitors in clinical trials for cancers did not show significant benefits, there is still potential for their application in research on other diseases.
Article
Biochemistry & Molecular Biology
Paras Sehgal, Samatha Mathew, Ambily Sivadas, Arjun Ray, Jyoti Tanwar, Sushma Vishwakarma, Gyan Ranjan, K. Shamsudheen, Rahul C. Bhoyar, Abhishek Pateria, Elvin Leonard, Mukesh Lalwani, Archana Vats, Rajeev R. Pappuru, Mudit Tyagi, Saumya Jakati, Shantanu Sengupta, B. K. Binukumar, Subhabrata Chakrabarti, Inderjeet Kaur, Rajender K. Motiani, Vinod Scaria, Sridhar Sivasubbu
Summary: The study identified a novel vascular endothelial-associated lncRNA named VEAL2, which regulates endothelial permeability and function through interaction with PRKCB2, and is implicated in diabetic retinopathy.
Article
Chemistry, Medicinal
Seyed-Omar Zaraei, Nour N. Al-Ach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Rimas T. Tokatly, Rawan R. Kalla, Mouna A. Munther, Marwa M. Wahba, Aya M. Alshihabi, Mahmoud K. Shehata, Rawan M. Sbenati, Afnan I. Shahin, Raafat El-Awady, Taleb H. Al-Tel, Mohammed I. El-Gamal
Summary: This article presents the design, synthesis, and biological screening results of a new series of diarylurea and diarylamide derivatives with a quinoline core armed with dimethylamino or morpholino side chains. The compounds showed broad-spectrum antiproliferative activity against a panel of 60 cancer cell lines, with three of them demonstrating higher potency than the reference drug, sorafenib. The compounds also exhibited high selectivity for C-RAF kinase, making them potential inhibitors for this molecular target.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(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)