European Journal of Medicinal Chemistry This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Ligand-based design and synthesis of new trityl histamine and trityl cysteamine derivatives as SIRT2 inhibitors for cancer therapy
This study presents an extensive SAR study of our reported trityl scaffold-based SIRT2 inhibitors. This study encompasses a range of different medicinal chemistry approaches to improve the activity of the lead compounds TH-3 and STCY1. The rationally designed and synthesized structures were confirmed using NMR and high-resolution mass spectroscopy before performing SIRT2 inhibition assay, NCI60 cytotoxicity test, and cell cycle analysis. Indeed, our strategies afforded hitherto unreported SIRT2 inhibitors with high activity, particularly 2a, 4a, 7c, and 7f. Remarkably, the presence of a lipophilic para substitution on the ...
Source: European Journal of Medicinal Chemistry - March 14, 2024 Category: Chemistry Authors: Mostafa M Badran Samar H Abbas Hiroshi Tateishi Yuki Maemoto Tsugumasa Toma Akihiro Ito Mikako Fujita Masami Otsuka Mohamed Abdel-Aziz Mohamed O Radwan Source Type: research

Scaffold hopping derived novel benzoxazepinone receptor-interacting protein kinase 1 (RIP1) inhibitors as anti-necroptosis agents: Anti-inflammatory effect in systemic inflammatory response syndrome (SIRS) and epilepsy
Eur J Med Chem. 2024 Mar 9;269:116304. doi: 10.1016/j.ejmech.2024.116304. Online ahead of print.ABSTRACTNecroptosis is a type of regulated cell death known for its pro-inflammatory nature due to the substantial release of cellular contents. The phosphorylation of key proteins, namely RIP1, RIP3, and mixed lineage kinase domain-like protein (MLKL), plays a pivotal role in the processes associated with necroptosis. Consequently, inhibiting the phosphorylation of any of these three key protein kinases could effectively block necroptosis. Utilizing a scaffold hopping strategy, we have successfully designed and synthesized a se...
Source: European Journal of Medicinal Chemistry - March 14, 2024 Category: Chemistry Authors: Ruiqi Jiang Bin Xu Shumeng Zhi Lei Sun Baocong Yu Qing Huang Ying Shi Source Type: research

Research progress on asialoglycoprotein receptor-targeted radiotracers designed for hepatic nuclear medicine imaging
Eur J Med Chem. 2024 Feb 27;269:116278. doi: 10.1016/j.ejmech.2024.116278. Online ahead of print.ABSTRACTAsialoglycoprotein receptor (ASGPR) specifically recognizes glycans terminated with β-d-galactose or N-acetylgalactosamine. Its exclusive expression in mammalian hepatocytes renders it an ideal hepatic-targeted biomarker. To date, ASGPR-targeted ligands have been actively developed for drug delivery and hepatic imaging. This review provides a comprehensive summary of the progress achieved to-date in the field of developing ASGPR-targeted nuclear medicine imaging (NMI) radiotracers, highlighting the recent advancements ...
Source: European Journal of Medicinal Chemistry - March 13, 2024 Category: Chemistry Authors: Yuqi Hua Chunjing Yu Source Type: research

Discovery of 5-aminopyrido[2,3-d]pyrimidin-7(8H)-one derivatives as new hematopoietic progenitor kinase 1 (HPK1) inhibitors
Eur J Med Chem. 2024 Mar 5;269:116310. doi: 10.1016/j.ejmech.2024.116310. Online ahead of print.ABSTRACTHematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T-cell receptor signaling. While HPK1 is considered as a promising target for cancer immunotherapy, no small-molecule HPK1 inhibitors have been approved for cancer treatment. Herein, we report the discovery of a series of new HPK1 inhibitors with a 5-aminopyrido[2,3-d]pyrimidin-7(8H)-one scaffold. The most potent compound 9f inhibited HPK1 kinase activity with an IC50 of 0.32 nM in the time-resolved fluorescence resonance energy transfer (TR-FRET) assays...
Source: European Journal of Medicinal Chemistry - March 13, 2024 Category: Chemistry Authors: Xiaorong Qiu Rong Liu Huan Ling Yang Zhou Xiaomei Ren Fengtao Zhou Jinwei Zhang Weixue Huang Zhen Wang Ke Ding Source Type: research

Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by modification with oligomannose
This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, by conjugation of the N-terminus with varying sizes of oligomannose, which are DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. Mechanistic studies indicated the dual-target binding of the conjugates. Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in increased inhibition of the viral infection of TZM-b1 cells (EC50 = 0.3-0.8 vs. 1.4 nM). Pentamannosylated T20 (M5-T20) exhibited a stronger inhibitory effect on virus entry into DC-SIGN+ 293T cells compared with T20 (67% vs. 50% inhibit...
Source: European Journal of Medicinal Chemistry - March 13, 2024 Category: Chemistry Authors: Shuihong Cheng Mingyue Xu Mingli Li Yong Feng Lin He Tong Liu Liying Ma Xuebing Li Source Type: research

Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases
Eur J Med Chem. 2024 Mar 7;269:116292. doi: 10.1016/j.ejmech.2024.116292. Online ahead of print.ABSTRACTSelective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure-activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyrida...
Source: European Journal of Medicinal Chemistry - March 13, 2024 Category: Chemistry Authors: Scott H Henderson Fiona J Sorrell James M Bennett Oleg Fedorov Marcus T Hanley Paulo H Godoi Roberta Ruela de Sousa Sean Robinson Iva Hopkins Navratilova Jonathan M Elkins Simon E Ward Source Type: research

Structure-based approaches for the design of 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d][1,2,3]triazoles as tubulin polymerization inhibitors
In conclusion, this report shows a successful case of the structure-based design approach of a potent tubulin polymerization inhibitor for cancer treatment.PMID:38471357 | DOI:10.1016/j.ejmech.2024.116309 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - March 12, 2024 Category: Chemistry Authors: Mingxin Huang Hongyao Han Haoyuan Liu Runlai Liu Jiwei Li Mi Li Qi Guan Weige Zhang Dun Wang Source Type: research

Sulfone-based human liver pyruvate kinase inhibitors - Design, synthesis and in vitro bioactivity
Eur J Med Chem. 2024 Mar 5;269:116306. doi: 10.1016/j.ejmech.2024.116306. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a prevalent pathological condition characterised by the accumulation of fat in the liver. Almost one-third of the global population is affected by NAFLD, making it a significant health concern. However, despite its prevalence, there is currently no approved drug specifically designed for the treatment of NAFLD. To address this critical gap, researchers have been investigating potential targets for NAFLD drug development. One promising candidate is the liver isoform of pyruvate...
Source: European Journal of Medicinal Chemistry - March 12, 2024 Category: Chemistry Authors: Josipa Mati ć Fady Akladios Umberto Maria Battisti Liliana H åversen Amalyn Nain-Perez Anders Foller F üchtbauer Woonghee Kim Leticia Monjas Alexandra Rodriguez Rivero Jan Bor én Adil Mardinoglu Mathias Uhlen Morten Gr øtli Source Type: research

Discovery of novel peptide-dehydroepiandrosterone hybrids inducing endoplasmic reticulum stress with effective in vitro and in vivo anti-melanoma activities
Eur J Med Chem. 2024 Mar 7;269:116296. doi: 10.1016/j.ejmech.2024.116296. Online ahead of print.ABSTRACTSteroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide-dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-do...
Source: European Journal of Medicinal Chemistry - March 11, 2024 Category: Chemistry Authors: Juan Feng Yidong Liu Xia Tian Chen Shen Zhiqiang Feng Jingxu Zhang Xiangli Yao Meilin Pu Xuguang Miao Lan Ma Shouxin Liu Source Type: research