Article
Chemistry, Medicinal
Hanyu Sun, Tingting Du, Minjian Yang, Xue Liu, Xi Xue, Kai Chen, Xuli Lang, Xiaoguang Chen, Baolian Wang, Xiaojian Wang
Summary: This study identified a potential binding subpocket of glutaminase C (GAC) and discovered promising inhibitors with robust GAC inhibitory activity and antiproliferative activity. The inhibitors were found to regulate cellular metabolites and exhibit excellent antiproliferative activity. The study also proposed new strategies for the development of novel GAC inhibitors.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Fei Liu, Bin Wang, Yanlong Liu, Wei Shi, Zhongyuan Hu, Xiayun Chang, Xujing Tang, Ying Zhang, Hongjiang Xu, Ying He
Summary: In this study, we reported the design, synthesis, and structure-activity relationships (SARs) of N-(methyl-d3) pyridazine-3carboxamide derivatives as TYK2 inhibitors. Compound 24 exhibited acceptable inhibition activity against STAT3 phosphorylation and demonstrated satisfactory selectivities toward other members of JAK family. Moreover, compound 24 showed good stability profile in liver microsomal assay and reasonable pharmacokinetics (PK) exposures. In anti-CD40-induced colitis models, compound 24 was orally highly effective with no significant hERG and CYP isozymes inhibition. These findings highlight the potential of compound 24 as a candidate for the development of anti-autoimmunity diseases agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Oncology
Francesca Ascenzi, Claudia De Vitis, Marcello Maugeri-Sacca, Christian Napoli, Gennaro Ciliberto, Rita Mancini
Summary: Autophagy is an intracellular degradation system that interacts with lipid metabolism, where fatty acids play a crucial role. SCD1 plays a significant role in promoting cell proliferation and metastasis in cancer, but its role in autophagy remains controversial, potentially resulting in either cancer promotion or inhibition depending on cancer heterogeneity and plasticity.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Chemistry, Physical
Wei Luo, Qingyun Lin, Xue Ran, Wenpo Li, Bochuan Tan, Anqing Fu, Shengtao Zhang
Summary: The new pyridazine-based derivative EPD has been synthesized as a corrosion inhibitor for copper in sulfuric acid, showing high inhibition efficiency due to the formation of adsorption films on the copper surface. Both electrochemical and surface characterization studies support the favorable inhibition performance of EPD.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Setareh Moghimi, Somayeh Salarinejad, Mahsa Toolabi, Loghman Firoozpour, Seyed Esmaeil Sadat Ebrahimi, Fatemeh Safari, Fatemeh Madani-Qamsari, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Saeed Karima, Roya Pakrad, Alireza Foroumadi
Summary: This study reported the discovery of pyridazine-based 1,2,3-triazole derivatives as inhibitors of ?-glucosidase, showing significant inhibitory activities against yeast and rat ?-glucosidase enzymes. The most potent compound exhibited IC50 values of 58 and 73 ?M, with hydrophobic and hydrogen bonding interactions playing important roles in the stability of the ligand-enzyme complex. The in-vitro safety against normal cell lines was also evaluated, indicating the potential pharmaceutical value of these compounds.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Fei Liu, Bin Wang, Yanlong Liu, Wei Shi, Xujing Tang, Xiaojin Wang, Zhongyuan Hu, Ying Zhang, Yahui Guo, Xiayun Chang, Xiangyi He, Hongjiang Xu, Ying He
Summary: In this study, a series of novel derivatives that bind to the TYK2 pseudokinase domain were designed, synthesized, and evaluated. Compound 30 showed excellent inhibitory potency against STAT3 phosphorylation, along with good JAK isoform selectivity, in vivo and in vitro pharmacokinetic properties, and high oral effectiveness in autoimmune disease models. These findings suggest that compound 30 is a promising candidate for therapeutic applications in autoimmune diseases.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Medicine, Research & Experimental
Quentin Raas, Malu-Clair van de Beek, Sonja Forss-Petter, Inge M. E. Dijkstra, Abigail Deschiffart, Briana C. Freshner, Tamara J. Stevenson, Yorrick R. J. Jaspers, Liselotte Nagtzaam, Ronald J. A. Wanders, Michel van Weeghel, Joo-Yeon Engelen-Lee, Marc Engelen, Florian Eichler, Johannes Berger, Joshua L. Bonkowsky, Stephan Kemp
Summary: The study found that rerouting saturated fatty acids to monounsaturated fatty acids can alleviate lipid toxicity in X-linked adrenoleukodystrophy (ALD). The drug chloroquine increased the expression of the enzyme regulating saturated fatty acid saturation status, relieving toxicity. Additionally, activating liver X receptor (LXR) can also convert saturated fatty acids to monounsaturated fatty acids.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Shenglong Zhu, Jingwei Zhang, Wei Wang, Xuan Jiang, Yong Q. Chen
Summary: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a global prevalence that is increasing. Currently, there is no effective pharmacological therapy available for NAFLD. In this study, the role of Ndufb9 in adipogenesis and its potential as a target for NAFLD treatment were explored. It was found that Ndufb9 is up-regulated in adipogenesis and its effect is mediated through Scd1. Additionally, the inhibition of Scd1 by aramchol significantly blocks adipogenesis. These findings provide new insights into the understanding and treatment of NAFLD.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Review
Chemistry, Medicinal
Zhang-Xu He, Yun-Peng Gong, Xin Zhang, Li-Ying Ma, Wen Zhao
Summary: Identification of potent anticancer agents with high selectivity and low toxicity remains an ongoing challenge. Pyridazine, known for its advantageous physicochemical properties and antitumor potential, is considered a promising drug-like scaffold. This review focuses on the structure-activity relationship studies and design strategies of pyridazine derivatives as potential anticancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Clemence Hamze, Julie Brossier, Konstantin Karaghiosoff, Edouard Godineau, Paul Knochel
Summary: A regioselective tri- and tetra-functionalization of the pyridazine scaffold was achieved using two readily available building blocks, resulting in the synthesis of a range of pyridazine derivatives.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Geriatrics & Gerontology
Ferley A. Bedoya-Guzman, Mar Pacheco-Herrero, Ivan Daniel Salomon-Cruz, Angela Maria Barrera-Sandoval, Johanna Andrea Gutierrez Vargas, Javier Gustavo Villamil-Ortiz, Carlos Andres Villegas Lanau, Julian David Arias-Londono, Estela Area-Gomez, Gloria Patricia Cardona Gomez
Summary: This study identifies a novel convergence of BACE-1 and SCD1 in neurodegeneration and the segregation of pro-inflammatory phospholipids.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Bing-Yen Wang, Yuan-Yen Chang, Li-Yen Shiu, Yi-Ju Lee, Yu-Wei Lin, Yu-Shen Hsu, Hsin-Ting Tsai, Sung-Po Hsu, Li-Jen Su, Meng-Hsiu Tsai, Jing-Hong Xiao, Jer-An Lin, Chang-Han Chen
Summary: This study systematically investigated the expression patterns and clinical outcomes of SCD1 in multiple human cancers and found that SCD1 is dysregulated in several types of cancers and acts as a diagnostic biomarker. Using ESCC as an example, it was found that SCD1 is upregulated in ESCC tumor tissues and is associated with clinicopathological characteristics and poor survival outcomes. Additionally, the study revealed the potential therapeutic target of the miR-181a-5p/SCD1 axis for ESCC treatment.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Kui Xu, Xiaoshuai Zhang, Guopeng Liu, Wanzun Ma, Yu Yin, Ying Yin, Xi Chen, Xinyun Zhao, Jonathan L. Sessler, Zhan Zhang
Summary: The synthesis of pyridazine-bridged expanded rosarin 1 and a reduced precursor, semi-rosarinogen 2, are reported. Both 1 and 2 have distorted structures, as shown by single crystal X-ray diffraction analysis and theoretical calculations. These compounds can differentiate various thiols in organic solvents through species-specific color changes and reaction times.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Min-Yao Liu, Hong-Ming Li, Xin-Yu Wang, Ran Xia, Xiang Li, Yu-Jie Ma, Miao Wang, Hong-Sheng Zhang
Summary: This study identifies TIGAR as a potential regulator of ferroptosis resistance in the development of colorectal cancer. TIGAR expression is associated with resistance to ferroptosis and oxidative stress, and it exerts its effects through the ROS/AMPK/SCD1 signaling pathway.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Organic
Thomas M. McQueen, Samuel D. Griggs
Summary: A series of highly substituted 2-spiropiperidines were synthesized using a new method, enriching the conformationally distinct structural- and regio-isomers of previously reported compounds and expanding the potential for exploring three-dimensional chemical space.
TETRAHEDRON LETTERS
(2021)
Article
Engineering, Electrical & Electronic
G. Vertesy, I Tomas, B. Balint, Sz Gyimothy, J. Pavo, T. Uchimoto, T. Takagi
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2018)
Article
Engineering, Electrical & Electronic
Xiaojuan Xu, Hongli Ji, Jinhao Qiu, Toshiyuki Takagi
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2018)
Article
Materials Science, Characterization & Testing
Xiaojuan Xu, Hongli Ji, Jinhao Qiu, Jun Cheng, Yipeng Wu, Toshiyuki Takagi
NDT & E INTERNATIONAL
(2018)
Article
Chemistry, Physical
Satish Tailor, Alexander G. Rakoch, Alexandra A. Gladkova, Phan Van Truong, Daria M. Strekalina, Georgia Sourkouni, S. Y. Manjunath, Toshiyuki Takagi
SURFACE INNOVATIONS
(2018)
Article
Engineering, Electrical & Electronic
Shohei Ogata, Tetsuya Uchimoto, Toshiyuki Takagi, Gerd Dobmann
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2018)
Article
Engineering, Electrical & Electronic
Shejuan Xie, Panpan Xu, Wenlu Cai, Hong-En Chen, Haiqiang Zhou, Zhenmao Chen, Tetsuya Uchimoto, Toshiyuki Takagi
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2018)
Article
Engineering, Electrical & Electronic
Xiaojuan Xu, Hongli Ji, Jinhao Qiu, Toshiyuki Takagi
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2019)
Article
Engineering, Electrical & Electronic
Takanori Matsumoto, Tetsuya Uchimoto, Toshiyuki Takagi, Gerd Dobmann, Shinji Oozono, Hideki Yuya
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2019)
Article
Engineering, Electrical & Electronic
Hiroyuki Kosukegawa, Yuta Kiso, Yuki Yoshikawa, Ryoichi Urayama, Toshiyuki Takagi
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2019)
Article
Engineering, Electrical & Electronic
Hongjun Sun, Ryoichi Urayama, Mitsuo Hashimoto, Fumio Kojima, Tetsuya Uchimoto, Toshiyuki Takagi
INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS
(2019)
Article
Engineering, Electrical & Electronic
G. Vertesy, I. Tomas, B. Skrbek, T. Uchimoto, T. Takagi
IEEE TRANSACTIONS ON MAGNETICS
(2019)
Article
Chemistry, Physical
Anastasiia Tukmakova, Anna Novotelnova, Kseniia Samusevich, Andrey Usenko, Dmitriy Moskovskikh, Alexandr Smirnov, Ekaterina Mirofyanchenko, Toshiyuki Takagi, Hiroyuki Miki, Vladimir Khovaylo
Article
Materials Science, Multidisciplinary
Takanori Matsumoto, Tetsuya Uchimoto, Toshiyuki Takagi, Gerd Dobmann, Benjamin Ducharne, Shinji Oozono, Hideki Yuya
JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS
(2019)
Article
Engineering, Mechanical
Sho Takeda, Hiroyuki Miki, Julien Fontaine, Hiroyuku Takeishi, Toshiyuki Takagi
Article
Engineering, Mechanical
Sho Takeda, Hiroyuki Miki, Julien Fontaine, Matthieu Guibert, Hiroyuku Takeishi, Toshiyuki Takagi
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
