Article
Cell Biology
Joshua D. Frenster, Hediye Erdjument-Bromage, Gabriele Stephan, Niklas Ravn-Boess, Shuai Wang, Wenke Liu, Devin Bready, Jordan Wilcox, Bjorn Kieslich, Manuel Jankovic, Caroline Wilde, Susanne Horn, Norbert Strater, Ines Liebscher, Torsten Schoneberg, David Fenyo, Thomas A. Neubert, Dimitris G. Placantonakis
Summary: This study identifies PTK7 as an extracellular binding partner of GPR133 in glioblastoma, and shows that PTK7 enhances GPR133 signaling by binding to the N-terminal fragment of GPR133. This interaction is potentially relevant to the pathogenesis of glioblastoma.
Article
Chemistry, Medicinal
Francis S. Willard, David B. Wainscott, Aaron D. Showalter, Cynthia Stutsman, Wenzhen Ma, Guemalli R. Cardona, Richard W. Zink, Christopher M. Corkins, Qi Chen, Nathan Yumibe, Javier Agejas, Graham R. Cumming, Jose Miguel Minguez, Alma Jimenez, Ana Mateo, Ana M. Castano, Daniel A. Briere, Kyle W. Sloop, Ana B. Bueno
Summary: LSN3318839 is a positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), enhancing the activity of weak metabolite GLP-1(9-36)NH2 and full-length ligand GLP-1(7-36)NH2 through G protein-coupled signaling. Experiments show that the combination of LSN3318839 and GLP-1(9-36)NH2 produces insulin secretion and glucose lowering effects similar to GLP-1(7-36)NH2.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Kaleeckal G. Harikumar, Thomas Coudrat, Aditya J. Desai, Maoqing Dong, Daniela G. Dengler, Sebastian G. B. Furness, Arthur Christopoulos, Denise Wootten, Eduard A. Sergienko, Patrick M. Sexton, Laurence J. Miller
Summary: This study proposes a new strategy for improving obesity treatment by enhancing the action of the CCK receptor, reducing the likelihood of side effects and toxicity. By identifying positive allosteric modulators (PAMs) with minimal intrinsic agonist activity and studying their mechanisms of action, it is possible to correct abnormal signaling in high-cholesterol environments and develop more effective drugs. The research focuses on compound 1, a weak partial agonist with PAM activity, which enhances CCK signaling without inducing receptor internalization, providing a potential avenue for developing targeted therapies for metabolic regulation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Chemistry, Medicinal
Corinna Schuess, Oanh Vu, Nigam M. Mishra, Iain R. Tough, Yu Du, Jan Stichel, Helen M. Cox, C. David Weaver, Jens Meiler, Kyle A. Emmitte, Annette G. Beck-Sickinger
Summary: In this study, a novel positive allosteric modulator (PAM) VU0506013 targeting the Y4R receptor was identified. It showed nanomolar affinity and selectivity towards the Y4R and has potential for anti-obesity research.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Tehila Mizrachi, Oshrit Marsha, Karen Brusin, Yael Ben-David, Ganesh A. Thakur, Adi Vaknin-Dembinsky, Millet Treinin, Talma Brenner
Summary: GAT107, an ago-PAM of alpha 7 nAChR, can significantly reduce disease severity and neuroinflammation in EAE by activating the receptor, leading to decreased pro-inflammatory cytokine production and increased anti-inflammatory cytokine IL-10. It also alters the expression of immune cell markers and directly activates alpha 7 nAChR in immune cells of MS patients and healthy donors.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Pharmacology & Pharmacy
Liang Yang, Xiao Zhu, David B. Finlay, Hayley Green, Michelle Glass, Stephen B. Duffull
Summary: A unified mathematical model was developed to describe the allosteric modulation of CB1 receptor. A hypothetical transitional state, CP55940-CB1-Org27569, was identified as the key factor in explaining the modulation effect of Org27569. This model reveals a novel mechanism of allosteric modulation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Simon Lind, Dagny Olofsson Hoffmann, Huamei Forsman, Claes Dahlgren
Summary: By studying the effects of the FFA2R ligand GLPG0974 on neutrophil activation, we discovered that GLPG0974 acts as an antagonist, agonist, and positive modulator of FFA2R. It affects NADPH-oxidase activity and alters receptor-downstream signaling induced by the co-agonistic PAMs.
CELLULAR SIGNALLING
(2022)
Article
Multidisciplinary Sciences
Heng Zhang, Jia-Jia Lin, Ya-Kai Xie, Xiu-Zu Song, Jia-Yi Sun, Bei-Lei Zhang, Yun-Kun Qi, Zhen-Zhong Xu, Fan Yang
Summary: The authors have engineered a peptide called s-RhTx as a positive allosteric modulator of the TRPV1 channel. It enhances the activity of TRPV1, allowing for reversible elimination of pain-sensing nerve terminals, providing long-lasting analgesia without affecting mice body temperature.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Stefano Salamone, Giovanni Appendino, Adil Khalili, Federica Pollastro, Eduardo Munoz, Juan D. Unciti-Broceta
Summary: The neutral fraction of juniper berries acetone extract could positively modulate the activity of CB1R, with the diterpenoid agathadiol identified as a positive allosteric modulator. Agathadiol, a minor constituent of juniper, can be more easily obtained through semisynthesis from agathic acid, a major constituent of Manila copal.
Article
Chemistry, Medicinal
Madeline F. Long, Rory A. Capstick, Paul K. Spearing, Julie L. Engers, Alison R. Gregro, Sean R. Bollinger, Sichen Chang, Vincent B. Luscombe, Alice L. Rodriguez, Hyekyung P. Cho, Colleen M. Niswender, Thomas M. Bridges, P. Jeffrey Conn, Craig W. Lindsley, Darren W. Engers, Kayla J. Temple
Summary: The Letter details efforts to develop novel tricyclic M-4 PAM scaffolds with improved pharmacological properties. A tie-back strategy was employed to replace the core structure, leading to the discovery of two novel tricyclic cores with low nanomolar potency against the human M-4 receptor.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Pharmacology & Pharmacy
Jacob T. Beckley, Teresa K. Aman, Michael A. Ackley, Tatiana M. Kazdoba, Michael C. Lewis, Anne C. Smith, Brandon J. Farley, Jing Dai, Wayne Deats, Ethan Hoffmann, Albert J. Robichaud, James J. Doherty, Michael C. Quirk
Summary: This study identified a neuroactive steroid NMDA receptor PAM called SAGE-718, which improves conditions associated with NMDA receptor hypofunction by increasing channel open probability.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Risa Okimoto, Katsutoshi Ino, Kenichiro Ishizu, Hajime Takamatsu, Kazuyuki Sakamoto, Hironori Yuyama, Hideyoshi Fuji, Akiyoshi Someya, Akiyoshi Ohtake, Takao Ishigami, Noriyuki Masuda, Masahiro Takeda, Shunichi Kajioka, Naoki Yoshimura
Summary: The novel M-3 receptor positive allosteric modulator ASP8302 enhances human M-3 receptor activation by interacting with a residue distinct from reported allosteric sites, suggesting not only a novel allosteric site of M-3 receptors but also potential application in diseases caused by insufficient M-3 receptor activation. This finding provides significant insight into further research on the allosteric modulation mechanism of M-3 and other muscarinic receptors.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Takaaki Mizuguchi, Kanako Miyano, Risa Yamauchi, Yuki Yoshida, Hideki Takahashi, Ami Yamazaki, Haruka Ono, Miku Inagaki, Miki Nonaka, Yasuhito Uezono, Hideaki Fujii
Summary: Positive allosteric modulators have the potential to enhance the activity of endogenous agonists with fewer side effects compared to exogenous orthosteric ligands. This study found that oxytocin functions as a positive allosteric modulator and identified the crucial structures of oxytocin for exerting this activity. These findings have implications for the development of novel analgesics.
Article
Pharmacology & Pharmacy
Moritaka Goto, Go Nishimura, Hirofumi Sato, Yu Yamaguchi, Nobutaka Morimoto, Hiroyuki Hashimoto, Naoki Takahashi
Summary: Upacicalcet is a non-peptide calcimimetic agent that shows potential as an alternative treatment for secondary hyperparathyroidism in chronic kidney disease. It activates the calcium-sensing receptor in a calcium concentration-dependent manner, without exhibiting agonistic activity at sub-physiological levels. Upacicalcet effectively reduces parathyroid hormone and serum calcium levels in rats, without affecting gastric emptying. Compared to other calcimimetics, it has good pharmacological properties and a lower risk of hypocalcemia and gastrointestinal complications.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Zhongtang Li, Guanxing Cai, Fan Fang, Wenchao Li, Minghua Fan, Jingjing Lian, Yinli Qiu, Xiangqing Xu, Xuehui Lv, Yiyan Li, Ruqiu Zheng, Yuxi Wang, Zhongjun Li, Guisen Zhang, Zhenming Liu, Zhuo Huang, Liangren Zhang
Summary: A series of furan-2-carboxamide analogues were identified as novel NMDAR-positive allosteric modulators, with FS2921 showing potential antidepressant effects. Compound 32h exhibited increased NMDAR excitability in vitro and significant antidepressant activity, with a favorable PK/PD profile. This study presents a new potential opportunity for discovering new antidepressants through novel NMDAR PAMs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Psychology, Biological
Umit Yilmaz, Kevser Tanbek
Summary: This study investigated the effects of intracerebroventricular administration of Spexin on the hypothalamus-pituitary-thyroid axis and energy expenditure in rats. The results showed that Spexin reduced food consumption and body weight, increased thyroid hormones, and enhanced energy metabolism.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Kuei-Yu Chien, Yun-Ju Chen, Kuo-Jen Hsu, Chiao-Nan Chen
Summary: This study investigated the effects of a high-protein diet and high-intensity interval training on appetite and weight loss in obese middle-aged individuals. The results showed that consuming a high-protein drink and following a high-protein diet after exercise can reduce post-exercise appetite and the frequency of late-night snacking.
PHYSIOLOGY & BEHAVIOR
(2024)
Review
Psychology, Biological
Melissa Alves Braga Oliveira, Ana Carolina Odebrecht Vergne de Abreu, Debora Barroggi Constantino, Andre C. Tonon, Antoni Diez-Noguera, Fernanda Gaspar Amaral, Maria Paz Hidalgo
Summary: Biological processes in living organisms exhibit strong rhythmicity and are regulated by internal timing systems. Understanding the influence of biological rhythms is crucial for experimental design and reporting.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Yanqun Cao, Hao Chen, Yinna Tan, Xu-Dong Yu, Chuli Xiao, Yin Li, James Reilly, Zhiming He, Xinhua Shu
Summary: There is evidence to suggest that chronic stress impacts neurochemical homeostasis and contributes to mental disorders. This study investigates the therapeutic potential of p-coumaric acid (p-CA), a natural compound found in vegetables and fruits, against stress-associated mental disorders. The findings suggest that p-CA could alleviate cognitive deficits and depression-like behavior in mice exposed to chronic restraint stress (CRS) by regulating the PKA-CREB-BDNF signaling pathway.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Mai O. Spaulding, Jessica R. Hoffman, Grace C. Madu, Magen N. Lord, Caroline Soares Iizuka, Kevin P. Myers, Emily E. Noble
Summary: Food insecurity is associated with obesity and disordered eating behaviors. Studying a rodent model, researchers found that adolescent food insecurity may increase susceptibility to obesity and altered eating behaviors during adulthood.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
K. Oberman, B. L. van Leeuwen, M. Nabben, J. E. Villafranca, R. G. Schoemaker
Summary: The present study investigated the post-operative complications and therapeutic potential of J147 in male Zucker rats, and found that J147 treatment had positive effects on behavioral and metabolic parameters, but did not affect neuroinflammation. The results suggest that a combination of acute and chronic J147 treatment may be optimal for treatment.
PHYSIOLOGY & BEHAVIOR
(2024)
Review
Psychology, Biological
Mathieu Cournoyer, Alice Maldera, Alexandre-Charles Gauthier, Fabien Dal Maso, Marie-Eve Mathieu
Summary: This article provides a comprehensive view of the literature on the effect of different odors on physical activity through a systematic review. It was found that pleasant odors have a positive impact on participants' physical activity. However, better methodological consistency is needed in studies to produce more meaningful results.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Gabriel R. Gilmore, Jeff Dyche
Summary: This study examined sleep, sleep/wake regularity, and cognition in college students diagnosed with depression and using serotonergic antidepressants, comparing them to those without a depression diagnosis. The results showed that students using antidepressants had slightly longer wake after sleep onset and lower sleep efficiency, but these differences were likely not noticed by the participants. There were no differences in sleep regularity or cognition between the two groups.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Erica A. Cross, Kim L. Huhman, H. Elliott Albers
Summary: Social stress plays a significant role in the development of neuropsychiatric disorders and can lead to behavioral deficits such as social withdrawal. This study investigates the impact of social stress on social reward in Syrian hamsters. The results show that subordinate and socially defeated males have reduced motivation for social interactions compared to dominant males. Additionally, winning males exhibit greater activation in the mesolimbic dopamine system compared to losers. In females, there were no differences in social entries between winners and losers, but winning females display more activation in the NAc shell.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Daniel A. R. Cabral, Maria L. M. Rego, Eduardo B. Fontes, Vagner D. O. Tavares
Summary: This study examined the association between body mass index (BMI) and negative emotional states (NES) in men with substance use disorders (SUD) undergoing treatment. The findings showed a positive correlation between BMI and stress, anxiety, and depression. These results suggest that reducing body fat accumulation may contribute to improving mental health in individuals with SUD during recovery.
PHYSIOLOGY & BEHAVIOR
(2024)
Review
Psychology, Biological
Elizabeth Agbor Epse Muluh, Jessica C. McCormack, Yunfan Mo, Michael Garratt, Mei Peng
Summary: This PROSPERO pre-registered systematic review and meta-analysis evaluated the olfactory and gustatory changes in pregnant individuals. The meta-analysis revealed that pregnant individuals performed poorer in odour identification, rated olfactory stimuli to be more intense during the second and third trimester, and had increased pleasantness for sweet taste in the first trimester. No major difference was observed in terms of gustatory functions between pregnant and non-pregnant subjects.
PHYSIOLOGY & BEHAVIOR
(2024)
Article
Psychology, Biological
Renee Spiteri Douglas, Mackenzie R. Hartley, J. Renee Yang, Tamara B. Franklin
Summary: The expression of Hdac2 in the hippocampus is associated with social status, while the expression of closely related genes Hdac1 and HDAC2 protein is not associated with social rank in the hippocampus.
PHYSIOLOGY & BEHAVIOR
(2024)
