Article
Chemistry, Medicinal
Sebastian Schieferdecker, Esther Vock
Summary: Toxicity, particularly off-target effects, is a major reason for the failure in pharmaceutical development. This study focuses on identifying the key amino acid residues in the active site of 5-HT2B receptor through molecular dynamics simulations. Pharmacophore models were developed and their performance was evaluated on in-house data and a diverse subset of Enamine REAL. Machine learning was used to label the subset for 5-HT2B activity. These models can serve as filters for early detection of compounds with potential 5-HT2B off-target liabilities.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Orr Shahar, Alexander Botvinnik, Noam Esh-Zuntz, Michal Brownstien, Rachel Wolf, Amit Lotan, Gilly Wolf, Bernard Lerer, Tzuri Lifschytz
Summary: There is growing interest in the therapeutic potential of psilocybin. This study examined the role of different serotonergic receptors and TAAR1 in modulating the head twitch response induced by 5-HTP and psilocybin in mice. The findings suggest that compounds that modulate psychedelic-induced head twitch response may have important therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elena Yu. Rybakova, Piotr P. Avdonin, Sergei K. Trufanov, Nikolay V. Goncharov, Pavel V. Avdonin
Summary: This study investigates the regulation of intracellular calcium concentration in human umbilical vein endothelial cells by 5-HT1B and 5-HT2B receptors. The findings suggest that simultaneous activation of both receptors leads to a synergistic increase in calcium concentration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jelena Nikolic, Katarina Vukojevic, Violeta Soljic, Josip Miskovic, Martina Orlovic Vlaho, Mirna Saraga-Babic, Natalija Filipovic
Summary: We studied the expression of serotonin receptors 5-HT1A, 5-HT2A, and 5-HT3A at different stages of fetal lung development. The receptors were strongly expressed in the epithelium of the proximal airways and vascular walls during early and mid-fetal development. In the later stages, they were also expressed in type I and type II pneumocytes. The expression of 5-HT2A decreased while 5-HT3A expression increased toward the final stage of lung development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Qi Mao, Bingjie Zhang, Sheng Tian, Wangzhi Qin, Jiaojiao Chen, Xi-Ping Huang, Ye Xin, Huicui Yang, Xue-Chu Zhen, Wenqing Shui, Na Ye
Summary: The concept of subtype selectivity and functional bias has had a significant impact on GPCR drug discovery. Through synthesis and evaluation, a series of new N-H aporphines were found to be potent and selective 5-HT2C receptor agonists. These agonists with an exclusive bias towards Gq signaling have the potential to be valuable pharmacological tools for understanding therapeutically relevant 5-HT2C signaling pathways and developing alternative antipsychotic medications.
BIOORGANIC CHEMISTRY
(2022)
Review
Nutrition & Dietetics
Edmund Przegalinski, Kacper Witek, Karolina Wydra, Jolanta H. Kotlinska, Malgorzata Filip
Summary: Obesity is a significant health and economic issue, and the serotonin system, specifically the 5-HT2C receptors, plays a crucial role in regulating body weight. This review focuses on the use of 5-HT2C receptor agonists as antiobesity medications, such as fenfluramines, sibutramine, and lorcaserin, and discusses the potential of 5-HT2C receptor positive allosteric modulators as safer alternatives. More research is needed to determine the efficacy of these drugs in obesity prevention and treatment.
Article
Behavioral Sciences
Rhayra Xavier do Carmo Silva, Bianca Gomes do Nascimento, Gabriela Cristini Vidal Gomes, Nadyme Assad Holanda da Silva, Jessica Souza Pinheiro, Suianny Nayara da Silva Chaves, Ana Flavia Nogueira Pimentel, Bruna Patricia Dutra Costa, Anderson Manoel Herculano, Monica Lima-Maximino, Caio Maximino
Summary: The role of serotonin (5-HT) receptors in vertebrates in response to aversive stimuli remains unclear due to the existence of multiple specific receptors. Different aversive stimuli elicit responses at various threat levels, such as exploration, defensive behaviors, and freezing reactions. Exposure of adult zebrafish to a conspecific alarm substance showed that agnostic and antagonist of the 5-HT2C receptor had different effects on responses to different levels of threat.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Article
Medicine, Research & Experimental
Liyuan Mao, Fang Xin, Jie Ren, Shuai Xu, Haixia Huang, Xu Zha, Xinxin Wen, Guoqing Gu, Guang Yang, Yuan Cheng, Chen Zhang, Wei Wang, Xicheng Liu
Summary: This study demonstrates the dual functions of 5-HT/5-HT2B/TGF-beta signaling in the initiation and progression of colitis-associated cancer (CAC), with a critical role in tumor suppression but a promotion of cancer progression in the late-stage of CAC.
Article
Chemistry, Medicinal
Dilip K. Tosh, Maggie M. Calkins, Marko S. Ivancich, Hailey A. Bock, Ryan G. Campbell, Sarah A. Lewicki, Eric Chen, Zhan-Guo Gao, John D. Mccorvy, Kenneth A. Jacobson
Summary: Derivatives of (N)-Methanocarba adenosine were modified to target 5-HT2B serotonin receptors as antagonists, showing affinity enhancement with the bicyclic ring system. Compound 43 (MRS7925) exhibited potential for anti-fibrotic therapy due to its affinity and moderate 5-HT2BR binding selectivity. The compounds also demonstrated dual action as 5-HT2B antagonists and A(1)AR agonists.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Gastroenterology & Hepatology
Byungchang Jin, Se Eun Ha, Lai Wei, Rajan Singh, Hannah Zogg, Brooke Clemmensen, Dante J. Heredia, Thomas W. Gould, Kenton M. Sanders, Seungil Ro
Summary: Enhancing HTR2B signaling can improve impaired colonic motility in diabetic mice, providing therapeutic benefits for constipation associated with diabetes.
Article
Chemistry, Medicinal
Christian B. M. Poulie, Eline Pottie, Icaro A. Simon, Kasper Harpsoe, Laura D'Andrea, Igor V. Komarov, David E. Gloriam, Anders A. Jensen, Christophe P. Stove, Jesper L. Kristensen
Summary: This study evaluated the biased signaling of the 5-HT2AR receptor and found that the interaction with Ser159(3x36) is crucial for signaling and efficacy. G alpha(q)-mediated signaling was more affected. These findings contribute to the development of more effective 5-HT2AR agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Alexandra J. Ng, Lindsay K. Vincelette, Jiayi Li, Bridget H. Brady, John P. Christianson
Summary: Behaviors associated with distress can influence the anxiety-like states in observers and shape social interactions among stressed individuals. Serotonin and its receptors, particularly the 5-HT2C receptor, play a crucial role in modulating social affective decision-making and are involved in the social reactions to stressed individuals. Furthermore, these effects are not influenced by gender.
Article
Biochemistry & Molecular Biology
Xuefeng Zhang, Chenglin He, Mu Wang, Qingtong Zhou, Dehua Yang, Ya Zhu, Wenbo Feng, Hui Zhang, Antao Dai, Xiaojing Chu, Jia Wang, Zhenlin Yang, Yi Jiang, Ulrich Sensfuss, Qiuxiang Tan, Shuo Han, Steffen Reedtz-Runge, H. Eric Xu, Suwen Zhao, Ming-Wei Wang, Beili Wu, Qiang Zhao
Summary: Cholecystokinin receptors CCKAR and CCKBR play important roles in food intake and appetite regulation. Crystal structures and cryo-EM structures reveal the recognition pattern of different ligands and the activation mechanism of receptors, providing atomic details for potential therapeutic development targeting cholecystokinin receptors.
NATURE CHEMICAL BIOLOGY
(2021)
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
Pharmacology & Pharmacy
Austen B. Casey, Munmun Mukherjee, Ryan P. McGlynn, Meng Cui, Stephen J. Kohut, Raymond G. Booth
Summary: This study elucidates the selective binding of novel 4-PATs compounds to 5-HT2A and 5-HT2C receptors. Ligand-receptor interactions in transmembrane domain 5 can be optimized to achieve selectivity for these compounds in antipsychotic drug development. Chirality can be exploited to attain selectivity over H-1 receptors, thereby circumventing sedative effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Wenyi Bian, Xueli Shen, Huang Tan, Xing Fan, Yunxia Liu, Haiping Lin, Youyong Li
Summary: The intrinsic coordinating effect of Fe single-atom catalysts in propane dehydrogenation was systematically studied using density functional theory (DFT) calculations. The Fe-N3P-C dual-coordinated site exhibited superior catalytic activity and selectivity at industrial temperatures due to its in-plane configuration that promotes C-H bond scission and offers an appropriate H diffusion rate, ensuring high propylene selectivity and catalyst regeneration.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Physical
Xinnan Mao, Lu Wang, Youyong Li
Summary: In this work, we developed a strategy combining high-throughput density functional theory (DFT) and machine learning (ML) techniques to discover IrO2-based electrocatalysts with enhanced oxygen evolution reaction (OER) activity. We considered 36 metal dopants to substitute for Ir and evaluated the most stable surface structures from a total of 4648 structures for OER activity. By using a neural network language model (NNLM), we associated the atomic environment with the formation energies of crystals and free energies of OER intermediates, and screened a series of potential candidates as superior OER catalysts. Our strategy efficiently explores promising electrocatalysts, particularly for evaluating complex multi-metallic compounds.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Nanoscience & Nanotechnology
Xiaomin Nie, Yujin Ji, Yi-min Ding, Youyong Li
Summary: Due to limited supply of lithium, the development of non-Li-ion batteries has become a research focus. In this study, the performance of chalcogenide-terminated MXenes as electrodes for Li-ion and non-Li-ion batteries was investigated using first-principles calculations. Different stacking types were observed in O/Te and S/Se terminated Ti2C multilayers. Ti2CO2 was found to be a potential anode material for Na- and K-ion batteries, while Ti2CS2 and Ti2CSe2 showed promise for Na-, K-, and Ca-ion batteries. Among these materials, Ti2CS2 exhibited the highest ion capacity of 616 mAh g(-1). These findings may inspire further experimental and theoretical studies of Ti2C-MXenes as electrodes for metal-ion batteries.
Article
Multidisciplinary Sciences
Fan Liao, Kui Yin, Yujin Ji, Wenxiang Zhu, Zhenglong Fan, Youyong Li, Jun Zhong, Mingwang Shao, Zhenhui Kang, Qi Shao
Summary: In this study, a monoclinic phase iridium oxide nanoribbon with a space group of C2/m is successfully obtained, which is distinct from rutile iridium oxide with a stable tetragonal phase (P42/mnm). The formation mechanism of IrO2 nanoribbon is clearly revealed, with its further conversion to IrO2 nanosheet with a trigonal phase. Well-defined metastable phase nanostructures are a core issue for catalyst design.
NATURE COMMUNICATIONS
(2023)
Article
Materials Science, Multidisciplinary
Yuyan Liu, Yujin Ji, Yi-Min Ding, Youyong Li, Shuit-Tong Lee
Summary: In this study, a comprehensive investigation of the MA(2)Z(4) family as anodes for LIBs and SIBs was conducted based on first-principle calculations. It was found that there is a linear relationship between the lowest unoccupied states energy level and ion adsorption energy, where lower energy level leads to stronger adsorption. Among the MA(2)Z(4) materials, NbGe2N4 was predicted as the most promising candidate for LIBs and VSi2P4 was better for SIBs, with high theoretical capacities and low ion diffusion barriers. Additionally, both NbGe2N4 and VSi2P4 demonstrated good phase stabilities. This study explores the application prospects of MA(2)Z(4) materials in LIBs and SIBs and provides insights into their intrinsic electronic mechanisms.
Article
Chemistry, Multidisciplinary
Jie Feng, Zhihao Dong, Yujin Ji, Youyong Li
Summary: By introducing a dynamic embedding layer, we propose a universal graph neural network called CrystalGNN, which can automatically update atomic inputs during the training process. We train a model based on this framework to accurately predict the formation energies of 10,500 IrO2 configurations and discover 8 unreported metastable phases. Among them, C2/m-IrO2 and P62-IrO2 are identified as excellent electrocatalysts that can reach the theoretical OER overpotential limit at their most stable surfaces. Our self-learning-input CrystalGNN framework exhibits reliable accuracy, generalization, and transferring ability and successfully accelerates the bottom-up catalyst design to boost the OER activity.
Article
Chemistry, Physical
Zhihao Dong, Jie Feng, Yujin Ji, Youyong Li
Summary: We propose a self-learning-input graph neural network framework, called SLI-GNN, to predict the properties of both crystals and molecules. By using a dynamic embedding layer and the Infomax mechanism, the input features are dynamically updated and the average mutual information between local and global features is maximized. Experimental results show that our SLI-GNN achieves comparable performance to other GNNs in material property prediction, indicating promising potential for accelerating new material discovery.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Article
Multidisciplinary Sciences
Xinhui Li, Shan He, Yanda Jiang, Jian Wang, Yi Yu, Xiaofei Liu, Feng Zhu, Yimei Xie, Youyong Li, Cheng Ma, Zhonghui Shen, Baowen Li, Yang Shen, Xin Zhang, Shujun Zhang, Ce-Wen Nan
Summary: Polymer nanocomposites with optimized interfacial structures between nanoparticles and polymers can greatly enhance the material properties. In polar polymers, two interfacial layers, namely an inner bound polar layer and an outer polar layer, are observed around nanoparticles. This bilayer structure can significantly enhance the polarity-related properties of polymer nanocomposites.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Hongshuai Wang, Jie Feng, Zhihao Dong, Lujie Jin, Miaomiao Li, Jianyu Yuan, Youyong Li
Summary: Organic photovoltaics have gained global attention for their unique advantages in developing low-cost, lightweight, and flexible power sources. Researchers have proposed functional molecular design and synthesis to accelerate the discovery of ideal organic semiconductors. However, experimental screening of a wide range of organic compounds is prohibitively expensive. In this study, a framework combining a deep learning model and an ensemble learning model is developed for rapid and accurate screening of organic photovoltaic molecules. This framework establishes the relationship between molecular structure, properties, and device efficiency, providing an efficient method for developing new organic optoelectronic materials.
NPJ COMPUTATIONAL MATERIALS
(2023)
Article
Chemistry, Physical
Yanxia Ma, Yuyan Liu, Yujin Ji, Youyong Li
Summary: In this study, the structural stabilities, electronic properties, and hydrogen evolution performances of nine kinds of 2D M4/3B2 materials were investigated using density functional theory calculations. The results showed that most of the materials were stable and promising for hydrogen production, except for Cr4/3B2. Monolayers of metallic Ti4/3B2 and Ta4/3B2 were susceptible to oxidation in aqueous environments, but had optimal hydrogen adsorption free energies and exchange current densities.
MATERIALS TODAY ENERGY
(2023)
Article
Chemistry, Physical
Rongfeng Guan, Pan Wang, Yujin Ji, Youyong Li, Yang Song
Summary: In this work, the pressure-induced phase transitions of N2H4BH3 were studied using vibrational spectroscopy, X-ray diffraction, and density functional theory (DFT). It was found that N2H4BH3 exhibits remarkable structural stability up to 15 GPa, followed by two phase transitions. DFT calculations revealed that the stability of N2H4BH3 and the late phase transformations are related to the pressure-mediated evolutions of dihydrogen bonding frameworks, the compressibility, and the enthalpies of the high-pressure polymorphs. These findings provide important insights into the structures and bonding properties of N2H4BH3 for hydrogen storage applications.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Jie Feng, Yujin Ji, Youyong Li
Summary: We investigated the performance of copper alloys in NO electroreduction reaction (NORR) using first-principles calculations and machine learning (ML). We found that the adsorption energy of N atoms is an effective catalytic descriptor for NORR. By screening 140 copper alloys, Cu@Cu3Ni and Cu2Ni2@Cu3Ni were discovered with low limiting potentials and kinetic barriers. We constructed an accurate ML model predicting the adsorption energy and identified Ni as an optimal alloy element to enhance NORR activity. This work opens up new possibilities for efficient alloy catalyst design and ML-accelerated discovery of novel NORR catalysts.
JOURNAL OF MATERIALS CHEMISTRY A
(2023)
Article
Chemistry, Physical
Wenzhen Xu, Yunpeng Shu, Mengmeng Xu, Juan Xie, Youyong Li, Huilong Dong
Summary: In this study, the effect of strain engineering on the electrocatalysis of CO reduction reaction (CORR) by 2D transition metal embedded polyphthalocyanines (MPPcs) was computationally explored. It was found that only CrPPc under biaxial strain had the potential to significantly enhance the catalytic performance. The free energy diagrams showed that the optimal reaction pathway and rate-determining step were changed under specific biaxial strains, and applying 5% compressive strain on CrPPc resulted in unexpected electrocatalytic activity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Wentao Qi, Dong Zhai, Danna Song, Chengcheng Liu, Junxia Yang, Lei Sun, Youyong Li, Xingwei Li, Weiqiao Deng
Summary: Considering the global challenge of low-cost and efficient anti-COVID-19 drug production, we developed a low-cost and efficient synthesis route for favipiravir using improved retrosynthesis software. This route involves only 3 steps under safe and near-ambient air conditions, achieving a yield of 32% and cost of $1.54 per g. We also applied the same strategy to optimize the synthesis of sabizabulin. These synthetic routes are expected to contribute to the prevention and treatment of COVID-19.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Piao Wang, Changle Zhang, Jiabao Ding, Yujin Ji, Youyong Li, Weifeng Zhang
Summary: Combining iridium dopants with highly active iridium atoms, Ir-SMO exhibits excellent performance for water oxidation in acidic conditions, making it an efficient and stable electrocatalyst.
