Article
Chemistry, Multidisciplinary
Yanyun Hao, Hui Li, Xiaoyan Ge, Yang Liu, Xia Li, Yutong Liu, Hongfei Chen, Shiying Zhang, Jing Zou, Lingling Huang, Fabao Zhao, Dongwei Kang, Bruno G. De Geest, Zhiyue Zhang
Summary: In this study, a polymeric nano-immunomodulator was developed to selectively activate the immune system in tumors, enhancing T lymphocyte infiltration without causing immune-related adverse effects. It shows promising potential for safe systemic targeting delivery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Zexiong Pan, Jianying Zhang, Lulu Guo, Hao Yang, Jianfeng Li, Chunming Cui
Summary: The research synthesized cyclic (alkyl)(amino)carbene lanthanide complexes and characterized their structures through X-ray diffraction analysis, with density functional theory calculations demonstrating the predominantly ionic bond nature of the complexes. One of the complexes also demonstrated catalytic hydrosilylation of alkenes with high yields and Markovnikov selectivity.
INORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Jaromir Vlach, Andrew T. Bender, Melinda Przetak, Albertina Pereira, Aditee Deshpande, Theresa L. Johnson, Sonja Reissig, Evgeni Tzvetkov, Djordje Musil, Noune Tahmassian Morse, Philipp Haselmayer, Simone C. Zimmerli, Shinji L. Okitsu, Robert L. Walsky, Brian Sherer
Summary: This study details the discovery and characterization of a novel toll-like receptor (TLR) 7 and TLR8 inhibitor (M5049), demonstrating its potential for treating autoimmune diseases in two mouse lupus models. The unique aspect of TLR7/8 inhibition is its ability to block both innate and adaptive autoimmunity, suggesting that M5049 could benefit patients with autoimmune diseases.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Jiaoyu Wu, Linqiang Li, Mengtian Liu, Lu Bai, Xinjun Luan
Summary: A novel Pd-0-catalyzed [2+2+1] annulation was proposed for the rapid assembly of tricyclic indoles in a single-step transformation. Experimental results showed that large tert-butyl and benzyl groups were selectively cleaved via an S(N)1 pathway in the presence of smaller alkyl groups.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Anne Huppertsberg, Leonard Kaps, Zifu Zhong, Sascha Schmitt, Judith Stickdorn, Kim Deswarte, Francis Combes, Christian Czysch, Jana De Vrieze, Sabah Kasmi, Niklas Choteschovsky, Adrian Klefenz, Carolina Medina-Montano, Pia Winterwerber, Chaojian Chen, Matthias Bros, Stefan Lienenklaus, Niek N. Sanders, Kaloian Koynov, Detlef Schuppan, Bart N. Lambrecht, Sunil A. David, Bruno G. De Geest, Lutz Nuhn
Summary: pH-responsive nanogels were fabricated for safe delivery of TLR7/8-stimulating imidazoquinolines, showing a spatially controlled immunostimulatory activity in the spleen after intravenous injection, without causing systemic off-target inflammatory responses. This approach highlights the potential of pH-degradable nanogels as a promising platform for intravenous administration of small-molecular TLR7/8 agonists in immune therapeutic applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Immunology
Irene Veneziani, Claudia Alicata, Lorenzo Moretta, Enrico Maggi
Summary: Toll-like receptors (TLRs) are described as homo- or heterodimeric proteins mainly in antigen presenting cells like dendritic cells (DCs), but recent studies have discovered their expression and role also in natural killer (NK) cells. The activation and function of TLRs can be modulated directly or indirectly by TLR agonists. The interplay between DCs and NK cells, mediated by cell-to-cell contact and soluble factors, promotes DC maturation and NK cell activation. Based on this concept, TLR-based immunotherapy targeting the NK-DC axis has been proposed to modulate the tumor microenvironment, improve DC antigen presentation, and enhance NK cell cytotoxicity against tumor cells.
IMMUNOLOGY LETTERS
(2023)
Article
Chemistry, Organic
Ying Lv, Li Chen, Kun Li, Xing-Han Yun, Sheng-Jiao Yan
Summary: A method for the synthesis of 2-(1H-imidazol-1-yl)-4H-chromen-4-one derivatives (IMCMs) was developed through a one-pot cascade reaction, involving various reactions such as 1,2-addition, Michael reaction, ring-closing, tautomerization, ring-opening, and [3 + 2] cyclization. This strategy not only enabled the synthesis of functionalized imidazoles (IMCMs), but also the synthesis of useful enamine building blocks, making it suitable for combinatorial and parallel syntheses of IMCMs.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Cell Biology
Anthony Ambesi, Pranav Maddali, Paula J. McKeown-Longo
Summary: The structural changes in the fibronectin matrix in the tumor microenvironment promote tumor progression by inducing the pro-tumorigenic cytokine IL-8 through activation of TLRs, resulting in the formation of an inflammatory microenvironment conducive to metastatic progression.
Review
Oncology
Hao Sun, Yingmei Li, Peng Zhang, Haizhou Xing, Song Zhao, Yongping Song, Dingming Wan, Jifeng Yu
Summary: Toll-like receptors (TLRs) are expressed in immune cells and tumors, playing roles in tumor immune surveillance and growth. Activation of TLR7/8 induces innate immune response and can be used as diagnostic and therapeutic targets in cancer.
BIOMARKER RESEARCH
(2022)
Article
Chemistry, Medicinal
Ratna Kumar Sreekantha, Christopher P. Mussari, Dharmpal S. Dodd, Laxman Pasunoori, Subramanya Hegde, Shana L. Posy, David Critton, Stefan Ruepp, Murali Subramanian, Luisa M. Salter-Cid, Debarati Mazumder Tagore, Sanket Sarodaya, Shailesh Dudhgaonkar, Michael A. Poss, Gary L. Schieven, Percy H. Carter, John E. Macor, Alaric J. Dyckman
Summary: Toll-like receptors are crucial for activation of the innate immune system. Aberrant activation of TLR7 and TLR8 can lead to autoimmune disorders, and inhibition of their signaling holds promise for disease treatment. A study identified potent dual inhibitors of TLR7 and TLR8, which selectively targeted these receptors and showed promising in vitro and in vivo results.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Long-Fei Li, Grace G-L Yue, Ben C-L Chan, Qiang Zeng, Quan-Bin Han, Ping-Chung Leung, Kwok-Pui Fung, Ji-Kai Liu, Clara B-S Lau
Summary: The water-soluble components of edible mushroom Rubinoboletus ballouii were investigated for their immunomodulatory properties. Polysaccharides of Rubinoboletus ballouii were found to promote the maturation of dendritic cells and increase the secretion of certain cytokines. In addition, these polysaccharides showed potential for restoring immune function in immunosuppressed mice.
PHYTOTHERAPY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Natsumi Ogawa, Shingo Nakajima, Kenya Tamada, Natsuki Yokoue, Haruki Tachibana, Miwa Okazawa, Takahiro Oyama, Hideaki Abe, Hiroaki Yamazaki, Atsushi Yoshimori, Akira Sato, Takanori Kamiya, Takehiko Yokomizo, Fumiaki Uchiumi, Takehiko Abe, Sei-ichi Tanuma
Summary: The spasmolytic drug trimebutine has shown potential as an anti-inflammatory agent in experiments, reducing the production of various proinflammatory factors and significantly decreasing mortality in a mouse model of sepsis. Studies have found that trimebutine exerts its anti-inflammatory effects by inhibiting TLR signaling pathways and NF-kappa B activity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Chemistry, Medicinal
Mu Yang, Peter G. Larson, Lincoln Brown, John R. Schultz, Tamara A. Kucaba, Thomas S. Griffith, David M. Ferguson
Summary: This study investigates the effect of isomeric substitutions to the C2-butyl group of imidazoquinoline agonists on Toll-like receptors (TLR) 7 and 8. The results show that the conformations of the dimeric receptor complex are highly sensitive to steric perturbations, indicating the importance of the ligand binding pocket in regulating the receptor signal. This finding has significant implications for the design of immunomodulatory agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Immunology
Valtteri Kairaluoma, Niko Kemi, Heikki Huhta, Vesa-Matti Pohjanen, Olli Helminen
Summary: TLR5 expression is independently prognostic in HCC with a similar point estimate as previously known p53. High Ki67 and p53 expression are associated with 5-year overall- and disease-specific survival. Toll-like receptor 8 (TLR8) was not associated with patient survival in this study.
Review
Pharmacology & Pharmacy
Xuan Huang, Xiaoyong Zhang, Mengji Lu
Summary: TLR7 and TLR8 signaling pathways are favorable drug candidates for the treatment of immune disorders, with agonists and antagonists being used to enhance immune responses or reduce immune overreactions. Optimizing drug safety, efficacy, and specificity, as well as conducting detailed mechanistic studies, will contribute to the development of novel TLR7/8 immunomodulators and therapeutic strategies.
EXPERT OPINION ON DRUG DISCOVERY
(2021)