Editorial Material
Pharmacology & Pharmacy
Mark L. Mayer
Summary: Recent research reveals a surprising mechanism involving a partially activated agonist-bound closed state in glycine receptor activation, which is different from the previously identified shortlived 'flipped' state.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Hyejin Park, Un-Ho Jin, Gregory Martin, Robert S. Chapkin, Laurie A. Davidson, Kyongbum Lee, Arul Jayaraman, Stephen Safe
Summary: Unsubstituted flavone can induce gene expression in Caco2 cells and acts as an AhR agonist. The addition of hydroxyl groups can determine the activity of flavones, but the affinity of mono- and dihydroxyflavones to AhR is similar and cannot accurately predict their activity. Most AhR-inactive flavones also function as AhR antagonists.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Medicinal
Mingxu Ma, Yifei Yang, Guangying Du, Yusen Dai, Xiaoyin Zhu, Wenyan Wang, Hengwei Xu, Jianzhao Zhang, Lixia Zheng, Fangxia Zou, Huijie Yang, Bin Liu, Wanhui Liu, Liang Ye, Rui Zhang, Jingwei Tian
Summary: Based on the docking study of Pimavanserin, a series of novel Pimavanserin derivatives were designed and synthesized. Compound 7-16 exhibited significantly higher 5-HT2A receptor antagonist and inverse agonist activities than Pimavanserin, along with improved pharmacokinetics and safety profile.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Lili Chen, Ying Yun, Shimeng Guo, Xiaoyan Wang, Muya Xiong, Tingting Zhao, Tifei Xu, Jianhua Shen, Xin Xie, Kai Wang
Summary: Danuglipron is a representative small-molecule agonist of the glucagon-like peptide-1 receptor (GLP-1R) that has shown positive results in clinical trials for the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, it has limitations such as hERG inhibition, lower activity compared to endogenous GLP-1, and short action time. This study introduces a new class of 5,6-dihydro-1,2,4-triazine derivatives that eliminate hERG inhibition caused by danuglipron, and identifies compound 42 as a highly potent and selective GLP-1R agonist with improved efficacy and acceptable drug-like properties. Compound 42 demonstrates longer-lasting effects in reducing glucose excursion and inhibiting food intake, making it a feasible treatment for T2DM and obesity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Yiming Yin, Mengge Wang, Wenjie Gu, Lili Chen
Summary: Colorectal cancer is one of the most malignant cancers globally, with limited therapeutic options in advanced stages. The Farnesoid X receptor (FXR) plays a crucial role in slowing down CRC progression, and intestine-restricted FXR agonists might offer a potentially safer therapy.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Julio Caballero
Summary: The design of TRPV1 antagonists and agonists has advanced with the availability of near-atomic resolution TRPV1 structures. Understanding the ligand-binding forms of these compounds allows for a more thorough use of molecular modelling methods in rational drug design protocols. This study highlights the important interactions between TRPV1 and capsaicin-like compounds based on known pharmacophore and TRPV1 structures, offering valuable insights for the design of novel TRPV1 antagonists and agonists.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Agriculture, Multidisciplinary
Zhiqiang Sun, Min Lv, Weiwei Huang, Tianze Li, Hui Xu
Summary: Unlike conventional insecticides, some botanical insecticides can inhibit the growth of insect pests and cause malformed moths with vestigial wings. This study found that a specific compound (2a) not only resulted in the formation of vestigial wings in moths, but also decreased their fertility. Compound 2a may target the insulin receptor in specific tissues, leading to the observed effects. Furthermore, it was discovered that compound 2a can induce vestigial wings in a different species of pest, suggesting the potential use of insect insulin receptors as targets for developing new green insecticides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Francisco O. Battiti, Saheem A. Zaidi, Vsevolod Katritch, Amy Hauck Newman, Alessandro Bonifazi
Summary: This study investigates the role of regio- and stereochemistry in cyclic aliphatic linkers tethering pharmacophores targeting dopamine D-2 and D-3 receptors, introducing potent and selective agonists while modulating subtype selectivity in a stereospecific manner. The findings demonstrate a novel approach to modulate dopaminergic ligand pharmacology and introduce a new class of optically active cyclic linkers that can be utilized in expanding bitopic drug design towards other GPCRs. Extensive molecular docking studies support the pharmacological observations presented in the study.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Daniel Marx, Mohamed Wessam Alnouri, Sophie Clemens, Robin Gedschold, Yvonne Riedel, Ghazl Al Hamwi, Thanigaimalai Pillaiyar, Jorg Hockemeyer, Vigneshwaran Namasivayam, Christa E. Mueller
Summary: This study discovered a xanthine derivative that activates the main variant of MRGPRX4, and optimization resulted in analogs with high potency and metabolic stability. These compounds are promising tool compounds for exploring the potential of MRGPRX4 as a future drug target.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jae-Hoon Jung, In Hee Jang, Moon Young Yang, Sunhong Kim, Soo-Kyung Kim, William A. Goddard, Yong-Chul Kim
Summary: Chronic exposure to stress or unwanted stimuli can activate the KOR/DYN systems, leading to depressive states and psychiatric disorders. We discovered novel pyrazoloisoquinoline-based KOR beta-arrestin inverse agonists through synthesis, structure-activity relationships, optimization, and biological evaluations. The optimized compound 7q showed potent and selective beta-arrestin inverse agonism at KOR, with no activity at MOR and lower activities at DOR. Molecular dynamics simulations were used to predict the binding mode and propose a mechanism for the inverse agonism, revealing different interactions between the receptor and beta-arrestin in different OR subtypes.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jeppe Nielsen, Jakob Brandt, Thomas Boesen, Tina Hummelshoj, Rita Slaaby, Gerd Schluckebier, Poul Nissen
Summary: Insulin regulates glucose homeostasis by binding and activating the insulin receptor in an asymmetric manner. This study reveals how insulin binds at two distinct sites and disrupts the autoinhibited state, stabilizing the active state of the receptor.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Elena A. Golubeva, Mstislav I. Lavrov, Eugene V. Radchenko, Vladimir A. Palyulin
Summary: L-Glutamic acid is the main neurotransmitter in the CNS, with receptors that regulate synaptic transmission and various processes. The glutamate receptors, particularly those selective to AMPA, are important in neurological disorders and have attracted attention for drug development. This review focuses on advances in AMPA receptor ligands since 2017, covering agonists, antagonists, modulators, and ion channel blockers, as well as their mechanisms of action.
Article
Chemistry, Medicinal
Viktoria M. S. Kjaer, Loukas Ieremias, Viktorija Daugvilaite, Michael Luckmann, Thomas M. Frimurer, Trond Ulven, Mette M. Rosenkilde, Jon Vabeno
Summary: The research found that the agonist activity of the G protein-coupled receptor GPR183/EBI2 is influenced by the substitution pattern of one of the two distal phenyl rings, acting as a molecular efficacy-switch.
Article
Chemistry, Organic
Hendrik Jonas, Daniele Aiello, Bastian Frehland, Kirstin Lehmkuhl, Dirk Schepmann, Jens Koehler, Patrizia Diana, Bernhard Wuensch
Summary: Restrictive conformationally bicyclic KOR agonists were synthesized and the endo-configured bicyclic amines were obtained through hydrogenation and diastereoselective reductive amination. The enantiomerically pure KOR agonists with high KOR affinity demonstrated a potential close to the bioactive conformation of more flexible KOR agonists. Changing the configuration of potent and selective KOR agonists also led to potent and selective sigma(1) ligands.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Joao Pedro Ferreira, Zohra Lamiral, John J. McMurray, Karl Swedberg, Dirk J. van Veldhuisen, John Vincent, Patrick Rossignol, Stuart J. Pocock, Bertram Pitt, Faiez Zannad
Summary: The study findings suggest that patients with heart failure with reduced ejection fraction and insulin-treated diabetes benefit more from eplerenone compared to those with diabetes not treated with insulin and individuals without diabetes.
CIRCULATION-HEART FAILURE
(2021)
Review
Agronomy
Z. Q. Kuang, X. H. Zhang, J. J. Ma, J. L. Li, L. J. Zhou
ALLELOPATHY JOURNAL
(2018)
Article
Biochemistry & Molecular Biology
Xiao-Hong Zhang, Jiao Wu, Ji-Guang Huang, Li-Juan Zhou
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2018)
Article
Agronomy
Xiaohong Zhang, Tingfei Zhu, Xiaoyang Bi, Sifan Yang, Jiguang Huang, Lijuan Zhou
Summary: Evaluation of herbicidal activities and 3D-QSAR analysis on 39 berberine analogues revealed that introducing an electropositive group in the N-7, C-9 and C-10 positions may improve the inhibition rate, while the hydrophobicity of the C-10 position was associated with high activity. The study provides valuable insights for designing more potent herbicidal compounds in the future.
PEST MANAGEMENT SCIENCE
(2021)
Article
Agronomy
Dandan Li, Xiaoyang Bi, Jingjing Ma, Xiaohong Zhang, Keni Jiang, Xuezhen Zhu, Jiguang Huang, Lijuan Zhou
Summary: The study identified the mechanism of berberine inhibiting the root growth of Arabidopsis thaliana by affecting the expression of thalianol and marneral gene clusters. This provides new insights into identifying the molecular targets of berberine.
PEST MANAGEMENT SCIENCE
(2022)
Article
Engineering, Environmental
Yuyang Tian, Xiaohong Zhang, Yuqi Huang, Gang Tang, Yunhao Gao, Xi Chen, Zhiyuan Zhou, Yan Li, Xuan Li, Huachen Wang, Xueyang Yu, Yulu Liu, Guangyao Yan, Jialu Wang, Yongsong Cao
Summary: The use of prodrug self-assembly technology can reduce the toxicity of pesticides to aquatic organisms, while also maintaining insecticidal activity and being environmentally friendly.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Agriculture, Multidisciplinary
Yuyang Tian, Yuqi Huang, Xiaohong Zhang, Gang Tang, Yunhao Gao, Zhiyuan Zhou, Yan Li, Huachen Wang, Xueyang Yu, Xuan Li, Yulu Liu, Guangyao Yan, Jialu Wang, Yongsong Cao
Summary: Self-assembled nanotechnology is a promising strategy for improving the effective utilization of pesticides. By self-assembling into spherical nanoparticles, PB NPs based on PYR and BA exhibit synergistic antimicrobial activity against plant pathogens and can promote plant growth as nutrients, thereby reducing toxicity to plants.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Huachen Wang, Gang Tang, Zhiyuan Zhou, Xi Chen, Yulu Liu, Guangyao Yan, Xiaohong Zhang, Xuan Li, Yuqi Huang, Jialu Wang, Yongsong Cao
Summary: Self-assembled nanotechnology is a promising strategy to overcome problems caused by herbicide formulations, such as volatilization and leaching. In this study, stable fluorescent nanoparticles (AP NPs) based on the co-assembly of acifluorfen (ACI) and poly(salicylic acid) (PSA) were constructed. The co-assembly process improved the physiochemical properties and reduced the leaching property of ACI, making it suitable for agricultural production.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Engineering, Environmental
Xiaohong Zhang, Junfan Niu, Zhiyuan Zhou, Gang Tang, Guangyao Yan, Yulu Liu, Jialu Wang, Gaohua Hu, Jianhua Xiao, Weiyao Yan, Yongsong Cao
Summary: The low bioavailability of pesticides has led to resource waste, environmental pollution, and potential threats to human health. In this study, a novel polymeric micellar carrier was prepared to improve the utilization efficiency of a pesticide and reduce the risks during application. The results showed that the prepared micellar carrier exhibited excellent release properties and fungicidal activities, making it a potential alternative to conventional pesticide formulations.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Agriculture, Multidisciplinary
Xiaohong Zhang, Gang Tang, Zhiyuan Zhou, Huachen Wang, Xuan Li, Guangyao Yan, Yulu Liu, Yuqi Huang, Jialu Wang, Yongsong Cao
Summary: In this study, enzyme-responsive prodrug nanoparticles were prepared by covalently conjugating drugs with inversely polar groups via a cleavable bond, which showed excellent antibacterial efficacy and reduced harm to aquatic organisms.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
