Article
Medicine, Research & Experimental
Walaa Wadie, Sarah S. Mohamed, Enas A. Abd El-Haleim, Mohamed T. Khayyal
Summary: This study aimed to investigate the potential impact of niacin on colitis-induced depressive-like behavior in rats. The results showed that niacin significantly ameliorated DSS-induced behavioral deficits and alleviated macroscopic and microscopic colonic inflammatory changes. In addition, niacin restored blood-brain barrier integrity through GPR109A-mediated mechanisms.
Article
Biochemistry & Molecular Biology
Caroline E. Geisler, Kendra E. Miller, Susma Ghimire, Benjamin J. Renquist
Summary: The study indicates that niacin affects glucose and lipid metabolism through the GPR109a signaling pathway, but in some cases, there may be independent mechanisms of action. Knockout of GPR109a does not have a significant impact on the acute effects of niacin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Shilong Liu, Yueqin Qiu, Fang Gu, Xiaoming Xu, Shansen Wu, Zhenhao Jin, Li Wang, Kaiguo Gao, Cui Zhu, Xuefen Yang, Zongyong Jiang
Summary: This study found that niacin supplementation alleviated diarrhea and intestinal damage in weaned piglets by regulating the expression of AQPs and ZO-1. The protective effect of niacin was mediated through the GPR109A pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Weam W. Ibrahim, Rabab H. Sayed, Esraa A. Kandil, Walaa Wadie
Summary: This study found that niacin could ameliorate behavioral deficits and restore blood-brain barrier integrity in a ketamine-induced model of psychosis. These effects were partially mediated through the GPR109A receptor. Niacin may represent a potential target for therapeutic interventions to prevent or slow the progression of psychosis.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Wenjin Guo, Wen Li, Yingchun Su, Shu Liu, Xingchi Kan, Xin Ran, Yu Cao, Shoupeng Fu, Juxiong Liu
Summary: The research findings indicate that niacin inhibits inflammatory responses in mastitis through GPR109A, enhances defense mechanisms in the mammary gland, and protects mammary tissue. GPR109A may serve as a potential target for the treatment of mastitis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biology
Jin-Ran Chen, Haijun Zhao, Umesh D. Wankhade, Sree V. Chintapalli, Can Li, Dongzheng Gai, Kartik Shankar, Fenghuang Zhan, Oxana P. Lazarenko
Summary: This study shows that GPR109A deletion in mice leads to higher bone mass and strength, decreased osteoclast numbers, and suppressed bone resorption markers in bone marrow. Additionally, GPR109A deletion inhibits Wnt/beta-catenin signaling in osteoclast precursors, leading to reduced osteoclast differentiation and activity. Hippuric acid (HA) inhibits bone resorption and increases bone mass in wild type mice, but not in GPR109A knockout mice, indicating a role of GPR109A in mediating the effects of HA on bone resorption during skeletal development.
COMMUNICATIONS BIOLOGY
(2021)
Review
Cell Biology
Kyle Taing, Lawrence Chen, Han-Rong Weng
Summary: Neuroinflammation is crucial in the development of various neurological disorders and pathological pain conditions. GPR109A, a Gi protein-coupled receptor, is identified as a significant therapeutic target for controlling inflammation in different tissues and organs. This review summarizes the current knowledge regarding the role of GPR109A in neuroinflammation, with a focus on its pharmacological features and signaling pathways involved in alleviating neuroinflammation and symptoms in Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and pathological pain conditions.
NEURAL REGENERATION RESEARCH
(2023)
Article
Cell Biology
Xin Pan, Fang Ye, Peiruo Ning, Zhiyi Zhang, Xinyu Li, Binghao Zhang, Qian Wang, Geng Chen, Wei Gao, Chen Qiu, Zhangsong Wu, Jiancheng Li, Lizhe Zhu, Jiang Xia, Kaizheng Gong, Yang Du
Summary: This study reports four cryo-EM structures of human HCAR2-Gi1 complexes with or without agonists, revealing the recognition mechanism and pharmacophore features of HCAR2 agonists. The findings shed light on the design of new HCAR2-targeting drugs for better efficacy, selectivity, and fewer side effects.
Review
Nutrition & Dietetics
Tennekoon B. Karunaratne, Chijioke Okereke, Marissa Seamon, Sharad Purohit, Chandramohan Wakade, Amol Sharma
Summary: Multiple studies implicate dysbiosis in the pathogenesis of Parkinson's disease, with changes in the microbiome likely contributing to the disease process, particularly involving alterations in SCFA-producing bacteria and endotoxin-producing bacteria. GPR109A receptor plays a key role in controlling intestinal permeability and inflammatory cascade, with butyrate acting via this receptor to improve gut barrier function. Niacin and butyrate, as ligands for GPR109A, are important factors in modulating macrophage polarization and inflammatory responses in Parkinson's disease.
Review
Psychiatry
Sabrina H. Ansarey
Summary: Schizophrenia is a neuropsychiatric illness with complex etiology, where antipsychotics have limited effectiveness. The topical application of niacin may help identify patients at an ultra-high-risk stage, potentially leading to new treatment options. The review explores potential genetic mutations in the GPR109A-COX-prostaglandin pathway and the role of inflammatory mediators in the pathology of diminished flush response.
FRONTIERS IN PSYCHIATRY
(2021)
Review
Chemistry, Medicinal
Prajakta B. Kothawade, Asha B. Thomas, Sohan S. Chitlange
Summary: Hyperlipidemia is characterized by high levels of cholesterol and triglycerides in blood. Various classes of drugs are used for treatment, but niacin therapy can lead to side effects like flushing, glucose intolerance, and liver toxicity. Recently, GPR109A receptor agonists have shown promise for treating dyslipidemia.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Simon Strass, Johanna Geiger, Natascha Cloos, Nadja Spaeth, Sophia Geiger, Anna Schwamborn, Luciano De Oliveira da Cunha, Mariella Martorelli, Jan-Hinrich Guse, Thaisa Lucas Sandri, Michael Burnet, Stefan Laufer
Summary: Dimethyl fumarate (DMF) is approved for multiple sclerosis (MS) treatment, however, its mode of action is unclear. One hypothesis suggests that DMF acts on thiols, such as glutathione, to modulate the immune system. Another hypothesis proposes that the hydrolysis product of DMF, monomethyl fumarate (MMF), acts as a ligand to the fatty acid receptor GPR109A in immune cells' lysosomes.
INFLAMMOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jiaming Chen, Tongbin Lin, Shuchang Zhang, Xianhuai Yue, XingHong Liu, Caichi Wu, Yunyi Liang, Xiangfang Zeng, Man Ren, Fang Chen, Wutai Guan, Shihai Zhang
Summary: This study reveals the important role of GPR109A in milk synthesis, and how niacin and BHBA promote milk fat and protein synthesis through the GPR109A/G(i)/mTORC1 signaling pathway. Knockdown of GPR109A attenuated the effects of niacin on milk synthesis, indicating its crucial role in this process.
Article
Public, Environmental & Occupational Health
Vanio Andre Mugabe, Arlete Mahumane, Cynthia Sema, Erika Valeska Rossetto, Crescencio Sequeira Nhabomba, Neusa Fataha, Unicia Nyamula, Angelica Sotomane, Wilson Irugula, Benigno Canze, Osvaldo Frederico Inlamea, Uriel Kitron, Guilherme Sousa Ribeiro, Eduardo Samo Gudo
Summary: An outbreak of pellagra in Nhamatanda district, Mozambique, three months after cyclone Idai was found to be associated with factors such as being female, lower education level, and insufficient consumption of chicken and peanut before the cyclone hit. The cyclone exacerbated food shortages in households, leading to a significant increase in pellagra cases due to reduced niacin consumption.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2021)
Review
Endocrinology & Metabolism
Xiaogang Chu, Raghavan Pillai Raju
Summary: More than a century after the discovery of NAD(+), ongoing research continues to reveal its critical role in cellular energetics, inflammation, metabolism, and cell survival. Reduced levels of NAD(+) are associated with various metabolic and neurological diseases as well as aging, while increasing NAD(+) levels has been shown to improve healthspan and lifespan in animal models. Recent studies suggest a causal link between senescence, age-related reduction in tissue NAD(+), and enzymatic degradation of NAD(+).
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Chemistry, Medicinal
Daniel J. Buzard, Thomas O. Schrader, Xiuwen Zhu, Juerg Lehmann, Ben Johnson, Michelle Kasem, Sun Hee Kim, Andrew Kawasaki, Luis Lopez, Jeanne Moody, Sangdon Han, Yinghong Gao, Jeff Edwards, Jeremy Barden, Jayant Thatte, Joel Gatlin, Robert M. Jones
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
Thomas O. Schrader, Michelle Kasem, Albert Ren, Konrad Feichtinger, Bilal Al Doori, Jing Wei, Chunrui Wu, Huong Dang, Minh Le, Joel Gatlin, Kelli Chase, Jenny Dong, Kevin T. Whelan, Carleton Sage, Andrew J. Grottick, Graeme Semple
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Organic
Thomas O. Schrader, Michelle Kasem, Qi Sun, Chunrui Wu, Albert Ren, Graeme Semple
TETRAHEDRON LETTERS
(2016)
Article
Chemistry, Organic
Thomas O. Schrader, Xiuwen Zhu, Michelle Kasem, Sufang Li, Chunyan Liu, Albert Ren, Chunrui Wu, Graeme Semple
TETRAHEDRON LETTERS
(2018)
Article
Chemistry, Medicinal
Jason E. Imbriglio, Sookhee Chang, Rui Liang, Subharekha Raghavan, Darby Schmidt, Abby Smenton, Scott Tria, Thomas O. Schrader, Jae-Kyu Jung, Craig Esser, Andrew K. P. Taggart, Kang Cheng, Ester Carballo-Jane, M. Gerard Waters, James R. Tata, Steven L. Colletti
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2009)
Article
Chemistry, Medicinal
P. Douglas Boatman, Thomas O. Schrader, Michelle Kasem, Benjamin R. Johnson, Philip J. Skinner, Jae-Kyu Jung, Jerry Xu, Martin C. Cherrier, Peter J. Webb, Graeme Semple, Carleton R. Sage, Jens Knudsen, Ruoping Chen, Andrew K. Taggart, Ester Carballo-Jane, Jeremy G. Richman
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Medicinal
Graeme Semple, Philip J. Skinner, Tawfik Gharbaoui, Young-Jun Shin, Jae-Kyu Jung, Martin C. Cherrier, Peter J. Webb, Susan Y. Tamura, P. Douglas Boatman, Carleton R. Sage, Thornas O. Schrader, Ruoping Chen, Steven L. Colletti, James R. Tata, M. Gerard Waters, Kang Cheng, Andrew K. Taggart, Tian-Quan Cai, Ester Carballo-Jane, Dominic P. Behan, Daniel T. Connolly, Jeremy G. Richman
JOURNAL OF MEDICINAL CHEMISTRY
(2008)
Article
Chemistry, Medicinal
P. Douglas Boatman, Brett Lauring, Thomas O. Schrader, Michelle Kasem, Benjamin R. Johnson, Philip Skinner, Jae-Kyu Jung, Jerry Xu, Martin C. Cherrier, Peter J. Webb, Graeme Semple, Carleton R. Sage, Jens Knudsen, Ruoping Chen, Wen-Lin Luo, Luzelena Caro, Josee Cote, Eseng Lai, John Wagner, Andrew K. Taggart, Ester Carballo-Jane, Milton Hammond, Steven L. Colletti, James R. Tata, Daniel T. Connolly, M. Gerard Waters, Jeremy G. Richman
JOURNAL OF MEDICINAL CHEMISTRY
(2012)
Article
Chemistry, Organic
Thomas O. Schrader, Benjamin R. Johnson, Luis Lopez, Michelle Kasem, Tawfik Gharbaoui, Dipanjan Sengupta, Daniel Buzard, Christine Basmadjian, Robert M. Jones
Article
Chemistry, Medicinal
Daniel J. Buzard, Luis Lopez, Jeanne Moody, Andrew Kawasaki, Thomas O. Schrader, Michelle Kasem, Ben Johnson, Xiuwen Zhu, Lars Thoresen, Sun Hee Kim, Tawfik Gharbaoui, Dipanjan Sengupta, Lorene Calvano, Ashwin Krishnan, Yinghong Gao, Graeme Semple, Jeff Edwards, Jeremy Barden, Michael Morgan, Khawja Usmani, Chuan Chen, Abu Sadeque, Weichao Chen, Ronald J. Christopher, Jayant Thatte, Lixia Fu, Michelle Solomon, Kevin Whelan, Hussien Al-Shamma, Joel Gatlin, Ibragim Gaidarov, Todd Anthony, Minh Le, David J. Unett, Scott Stirn, Anthony Blackburn, Dominic P. Behan, Robert M. Jones
ACS MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Chemistry, Medicinal
Albert Ren, Xiuwen Zhu, Konrad Feichtinger, Juerg Lehman, Michelle Kasem, Thomas O. Schrader, Amy Wong, Huong Dang, Minh Le, John Frazer, David J. Unett, Andrew J. Grottick, Kevin T. Whelan, Michael E. Morgan, Carleton R. Sage, Graeme Semple
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Chemistry, Medicinal
Thomas O. Schrader, Yifeng Xiong, Ariana O. Lorenzana, Alexander Broadhead, Karin J. Stebbins, Michael M. Poon, Christopher Baccei, Daniel S. Lorrain
Summary: The discovery and development of PIPE-359, a brain-penetrant selective antagonist of the muscarinic acetylcholine receptor subtype 1, is described. This compound showed good permeability and selectivity, as well as robust efficacy in a preclinical model for multiple sclerosis. Initial modifications and iterative scanning led to improvements in metabolic and hERG profiles, ultimately resulting in the successful development of PIPE-359.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Thomas O. Schrader, Xiuwen Zhu, Michelle Kasem, Albert Ren, Chunyan Liu, Chunrui Wu, Huong Dang, Minh Le, Joel Gatlin, Kelli Chase, John Frazer, Kevin T. Whelan, Andrew J. Grottick, Clayton Hutton, Jeremy Barden, Chuan Chen, Alvaro Ortiz, Konrad Feichtinger, Graeme Semple
Summary: A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines have been identified as potent and selective agonists of the 5-HT2C receptor. Optimizations on a previously reported series of compounds have led to the discovery of an advanced drug lead with excellent in vitro and in vivo pharmacological profiles.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Tawfik Gharbaoui, Philip J. Skinner, Young-Jun Shin, Claudia Averbuj, Jae-Kyu Jung, Benjamin R. Johnson, Tracy Duong, Marc Decaire, Jane Uy, Martin C. Cherrier, Peter J. Webb, Susan Y. Tamura, Ning Zou, Nathalie Rodriguez, P. Douglas Boatman, Carleton R. Sage, Andrew Lindstrom, Jerry Xu, Thomas O. Schrader, Brian M. Smith, Ruoping Chen, Jeremy G. Richman, Daniel T. Connolly, Steven L. Colletti, James R. Tata, Graeme Semple
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2007)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
