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Malolactone strikes: K-Ras-G12D's Achilles' heel Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-22 Christos Adamopoulos, Kostas A. Papavassiliou, Athanasios G. Papavassiliou
In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles and designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical
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Heterobifunctional small molecules to modulate RNA function Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-18 Sandra Kovachka, Yuquan Tong, Jessica L. Childs-Disney, Matthew D. Disney
RNA has diverse cellular functionality, including regulating gene expression, protein translation, and cellular response to stimuli, due to its intricate structures. Over the past decade, small molecules have been discovered that target functional structures within cellular RNAs and modulate their function. Simple binding, however, is often insufficient, resulting in low or even no biological activity
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AML treatment: conventional chemotherapy and emerging novel agents Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-20 Mark Forsberg, Marina Konopleva
Acute myeloid leukemia (AML) is driven by complex mutations and cytogenetic abnormalities with profound tumoral heterogeneity, making it challenging to treat. Ten years ago, the 5-year survival rate of patients with AML was only 29% with conventional chemotherapy and stem cell transplantation. All attempts to improve conventional therapy over the previous 40 years had failed. Now, new genomic, immunological
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Electroceuticals: emerging applications beyond the nervous system and excitable tissues Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-18 Swarnalatha Balasubramanian, David A. Weston, Michael Levin, Devon Charles Cardoso Davidian
Electroceuticals have evolved beyond devices manipulating neuronal signaling for symptomatic treatment, becoming more precise and disease modulating and expanding beyond the nervous system. These advancements promise transformative applications in arthritis, cancer treatment, tissue regeneration, and more. Here, we discuss these recent advances and offer insights for future research.
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Direct in vivo CAR T cell engineering Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-12 Lauralie Short, Robert A. Holt, Pieter R. Cullis, Laura Evgin
T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers and have the potential to revolutionize therapy for many other diseases. To circumvent the complexity and cost associated with broad-scale implementation of ex vivo manufactured adoptive cell therapy products, alternative strategies
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Frizzleds act as dynamic pharmacological entities Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-08
Abstract not available
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Targeting methionine metabolism in cancer: opportunities and challenges Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-05 Peng Bin, Chuanlong Wang, Hangchao Zhang, Yuqi Yan, Wenkai Ren
Reprogramming of methionine metabolism is a conserved hallmark of tumorigenesis. Recent studies have revealed mechanisms regulating methionine metabolism within the tumor microenvironment (TME) that drive both cancer development and antitumor immunity evasion. In this review article we summarize advancements in our understanding of tumor regulation of methionine metabolism and therapies in development
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Advisory Board and Contents Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-04
Abstract not available
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Subscription and Copyright Information Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-04-04
Abstract not available
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Genetically engineered loaded extracellular vesicles for drug delivery Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-03-19 Zuriñe Erana-Perez, Manoli Igartua, Edorta Santos-Vizcaino, Rosa Maria Hernandez
The use of extracellular vesicles (EVs) for drug delivery is being widely explored by scientists from several research fields. To fully exploit their therapeutic potential, multiple methods for loading EVs have been developed. Although exogenous methods have been extensively utilized, in recent years the endogenous method has gained significant attention. This approach, based on parental cell genetic
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Leveraging macrophage metabolism for anticancer therapy: opportunities and pitfalls Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-03-17 Piyal Saha, Paul Ettel, Thomas Weichhart
Tumor-associated macrophages (TAMs) constitute an important part of the tumor microenvironment (TME) that regulates tumor progression. Tumor-derived signals, hypoxia, and competition for nutrients influence TAMs to reprogram their cellular metabolism. This altered metabolic profile creates a symbiotic communication between tumor and other immune cells to support tumor growth. In addition, the metabolic
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Targeting Fks1 proteins for novel antifungal drug discovery Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-03-15 Vinit Kumar, Juan Huang, Yawen Dong, Ge-Fei Hao
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Hepatic mitochondrial reductive stress in the pathogenesis and treatment of steatotic liver disease Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-03-12 Mari J. Jokinen, Panu K. Luukkonen
Steatotic liver diseases (SLDs) affect one-third of the population, but the pathogenesis underlying these diseases is not well understood, limiting the available treatments. A common factor in SLDs is increased hepatic mitochondrial reductive stress, which occurs as a result of excessive lipid and alcohol metabolism. Recent research has also shown that genetic risk factors contribute to this stress
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Targeting mitochondrial dynamics and redox regulation in cardiovascular diseases Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-03-07 Mirza Ahmar Beg, Minqi Huang, Lance Vick, K.N. Shashanka Rao, Jue Zhang, Yiliang Chen
Accumulating evidence highlights the pivotal role of mitochondria in cardiovascular diseases (CVDs). Understanding the molecular mechanisms underlying mitochondrial dysfunction is crucial for developing targeted therapeutics. Recent years have seen substantial advancements in unraveling mitochondrial regulatory pathways in both normal and pathological states and the development of potent drugs. However
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Translational adaptation in breast cancer metastasis and emerging therapeutic opportunities Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-03-06 Siyu Chen, Albertas Navickas, Hani Goodarzi
Breast cancer’s tendency to metastasize poses a critical barrier to effective treatment, making it a leading cause of mortality among women worldwide. A growing body of evidence is showing that translational adaptation is emerging as a key mechanism enabling cancer cells to thrive in the dynamic tumor microenvironment (TME). Here, we systematically summarize how breast cancer cells utilize translational
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VMAT structures reveal exciting targets for drug development Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-29 Shimon Schuldiner, Lucy R. Forrest
Vesicular monoamine transporter (VMAT)-2 has a crucial role in the neurotransmission of biogenic amines. Recently, Dalton et al., Pidathala et al., Wu et al., and Wang et al. individually reported cryo-electron microscopy (EM) structures of human VMAT2, offering opportunities for developing improved therapeutics and deep insights into the functioning of this protein.
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Mitochondrial DNA competition: starving out the mutant genome Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-23 Antonella Spinazzola, Diego Perez-Rodriguez, Jan Ježek, Ian J. Holt
High levels of pathogenic mitochondrial DNA (mtDNA) variants lead to severe genetic diseases, and the accumulation of such mutants may also contribute to common disorders. Thus, selecting against these mutants is a major goal in mitochondrial medicine. Although mutant mtDNA can drift randomly, mounting evidence indicates that active forces play a role in the selection for and against mtDNA variants
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Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-20 Jeffrey White, Frederick A. Derheimer, Kristen Jensen-Pergakes, Shawn O’Connell, Shikhar Sharma, Noah Spiegel, Thomas A. Paul
Lysine acetyltransferases (KATs) are a family of epigenetic enzymes involved in the regulation of gene expression; they represent a promising class of emerging drug targets. The frequent molecular dysregulation of these enzymes, as well as their mechanistic links to biological functions that are crucial to cancer, have led to exploration around the development of small-molecule inhibitors against KATs
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Recent advances in generative biology for biotherapeutic discovery Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-19 Marissa Mock, Christopher James Langmead, Peter Grandsard, Suzanne Edavettal, Alan Russell
Generative biology combines artificial intelligence (AI), advanced life sciences technologies, and automation to revolutionize the process of designing novel biomolecules with prescribed properties, giving drug discoverers the ability to escape the limitations of biology during the design of next-generation protein therapeutics. Significant hurdles remain, namely: (i) the inherently complex nature
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Alzheimer’s therapeutic development: shifting neurodegeneration to neuroregeneration Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-14 Miao-Kun Sun, Daniel L. Alkon
Alzheimer’s disease (AD), similar to AD-related dementias, is characterized by impaired/lost neuronal structures and functions due to a long progression of neurodegeneration. Derailed endogenous signal pathways and disease processes have critical roles in neurodegeneration and are pharmacological targets in inducing neuroregeneration. Pharmacologically switching/shifting the brain status from neurodegeneration
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Targeting chromosomal instability and aneuploidy in cancer Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-13 Sugandha Bhatia, Kum Kum Khanna, Pascal H.G. Duijf
Cancer development and therapy resistance are driven by chromosomal instability (CIN), which causes chromosome gains and losses (i.e., aneuploidy) and structural chromosomal alterations. Technical limitations and knowledge gaps have delayed therapeutic targeting of CIN and aneuploidy in cancers. However, our toolbox for creating and studying aneuploidy in cell models has greatly expanded recently.
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The role of NMR in advancing small molecule drug discovery Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-13 Leszek Poppe
Navigating the ever-evolving landscape of nuclear magnetic resonance (NMR) poses challenges for the industry. This work explores promising approaches that illuminate protein–ligand interactions in the context of structural dynamics, facilitating targeted drug discovery. I acknowledge existing limitations and highlight future opportunities, which may pave the way for broader NMR integration and faster
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Advances in inhibitor development targeting the PWWP domain Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-09 Yunyuan Huang, Yanxi Li, Jinrong Min
The PWWP domain binds to both histone and DNA of a nucleosome in a bivalent way. PWWP domain-containing proteins are involved in different biological processes, and their aberrant expression is implicated in various human diseases. Here, we discuss the recent developments and challenges in targeting the PWWP domain for therapeutic intervention.
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Advisory Board and Contents Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-01
Abstract not available
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Subscription and Copyright Information Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-02-01
Abstract not available
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Complex architecture of cardiac muscle thick filaments revealed Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-31 Pradeep K. Luther, Steve B. Marston
Muscle contraction is orchestrated by the well-understood thin filaments and the markedly complex thick filaments. Studies by . and , discussed here, have unravelled the structure of the mammalian heart thick filament in exquisite near-atomic detail and pave the way for understanding physiological modulation pathways and mutation-induced dysfunction and for designing potential drugs to modify defects
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The structure and function of olfactory receptors Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-31 Chenyang Wu, Marc Xu, Junlin Dong, Wenqiang Cui, Shuguang Yuan
Olfactory receptors (ORs) form the most important chemosensory receptor family responsible for our sense of smell in the nasal olfactory epithelium. This receptor family belongs to the class A G protein-coupled receptors (GPCRs). Recent research has indicated that ORs are involved in many nonolfactory physiological processes in extranasal tissue, such as the brain, pancreas, and testes, and implies
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Glymphatic-stagnated edema induced by traumatic brain injury Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-29 Per Kristian Eide, Geir Ringstad
Traumatic brain injury (TBI) outcomes are notably affected by brain edema. A recent report by Hussain et al. unveils a unique form, glymphatic-stagnated brain edema, that stems from impaired glymphatic and lymphatic drainage induced by noradrenergic activation. Consequently, pan-noradrenergic inhibition may emerge as an innovative treatment for TBI-related edema, challenging traditional therapeutic
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Mirikizumab (Omvoh™) for ulcerative colitis Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-22 Alexander Hammerhøj, Theresa Louise Boye, Ebbe Langholz, Ole Haagen Nielsen
Abstract not available
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Revisiting sensitivity of senescent cells to BH3 mimetics Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-20 Nadine Martin, Anda Huna, Athanasios Tsalikis, David Bernard
B cell leukemia/lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics were reported to selectively kill senescent cells and improve age-related diseases. Defining why these cells show increased sensitivity to these molecules will help to identify new pharmacological compounds with senolytic activity. Here, we discuss how recent research findings provide new clues to understand this vulnerability.
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Context-dependent role of SIRT3 in cancer Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-19 Jin Zhang, Jing Ye, Shiou Zhu, Bo Han, Bo Liu
Sirtuin 3 (SIRT3), an NAD+-dependent deacetylase, plays a key role in the modulation of metabolic reprogramming and regulation of cell death, as well as in shaping tumor phenotypes. Owing to its critical role in determining tumor-type specificity or the direction of tumor evolution, the development of small-molecule modulators of SIRT3, including inhibitors and activators, is of significant interest
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Leveraging spatial omics for the development of precision sarcoma treatments Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-11 Cui Tu, Arutha Kulasinghe, Andrew Barbour, Fernando Souza-Fonseca-Guimaraes
Sarcomas are rare and heterogeneous cancers that arise from bone or soft tissue, and are the second most prevalent solid cancer in children and adolescents. Owing to the complex nature of pediatric sarcomas, the development of therapeutics for pediatric sarcoma has seen little progress in the past decades. Existing treatments are largely limited to chemotherapy, radiation, and surgery. Limited knowledge
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Emerging epigenetic insights into aging mechanisms and interventions Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-11 Zeming Wu, Weiqi Zhang, Jing Qu, Guang-Hui Liu
Epigenetic dysregulation emerges as a critical hallmark and driving force of aging. Although still an evolving field with much to explore, it has rapidly gained significance by providing valuable insights into the mechanisms of aging and potential therapeutic opportunities for age-related diseases. Recent years have witnessed remarkable strides in our understanding of the epigenetic landscape of aging
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Do the therapeutic effects of psilocybin involve actions in the gut? Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-11 Felicia Reed, Claire J. Foldi
The psychedelic compound psilocybin has recently emerged as a therapeutic intervention for various mental health conditions. Psilocybin is a potent agonist of serotonin (5-HT) receptors (5-HTRs), which are expressed in the brain and throughout peripheral tissues, with particularly high expression in the gastrointestinal (GI) tract. However, no studies have investigated the possibility that peripheral
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Tumor iron homeostasis and immune regulation Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-11 Yan-Yu Zhang, Yi Han, Wen-Ning Li, Rui-Hua Xu, Huai-Qiang Ju
Abnormal iron metabolism has long been regarded as a key metabolic hallmark of cancer. As a critical cofactor, iron contributes to tumor progression by participating in various processes such as mitochondrial electron transport, gene regulation, and DNA synthesis or repair. Although the role of iron in tumor cells has been widely studied, recent studies have uncovered the interplay of iron metabolism
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Subscription and Copyright Information Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-04
Abstract not available
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Advisory Board and Contents Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-04
Abstract not available
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Metabolite-sensing GPCRs in rheumatoid arthritis Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2024-01-05 Xuezhi Yang, Wankang Zhang, Luping Wang, Yingjie Zhao, Wei Wei
Persistent inflammation in damaged joints results in metabolic dysregulation of the synovial microenvironment, causing pathogenic alteration of cell activity in rheumatoid arthritis (RA). Recently, the role of metabolite and metabolite-sensing G protein-coupled receptors (GPCRs) in the RA-related inflammatory immune response (IIR) has become a focus of research attention. These GPCRs participate in
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Harnessing deep learning for enhanced ligand docking Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-30 Xujun Zhang, Chao Shen, Chang-Yu Hsieh, Tingjun Hou
Ligand docking (LD), a technology for predicting protein–ligand (PL)-binding conformations and strengths, plays key roles in virtual screening (VS). However, the accuracy and speed of current LD methodologies remain suboptimal. Here, we discuss how deep learning (DL) could help to bridge this gap by examining recent advancements and projecting future trends.
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The rise of epitranscriptomics: recent developments and future directions Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-15 Jonas Cerneckis, Guo-Li Ming, Hongjun Song, Chuan He, Yanhong Shi
The epitranscriptomics field has undergone tremendous growth since the discovery that the RNA -methyladenosine (mA) modification is reversible and is distributed throughout the transcriptome. Efforts to map RNA modifications transcriptome-wide and reshape the epitranscriptome in disease settings have facilitated mechanistic understanding and drug discovery in the field. In this review we discuss recent
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Spatial pharmacology using mass spectrometry imaging Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-15 Presha Rajbhandari, Taruna V. Neelakantan, Noreen Hosny, Brent R. Stockwell
The emerging and powerful field of spatial pharmacology can map the spatial distribution of drugs and their metabolites, as well as their effects on endogenous biomolecules including metabolites, lipids, proteins, peptides, and glycans, without the need for labeling. This is enabled by mass spectrometry imaging (MSI) that provides previously inaccessible information in diverse phases of drug discovery
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Pharmacological targets at the lysosomal autophagy–NLRP3 inflammasome crossroads Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-14 Srinivasa Reddy Bonam, Dylan Mastrippolito, Philippe Georgel, Sylviane Muller
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Biomarkers and targeted therapy for cancer stem cells Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-09 Yusheng Liu, Hua Wang
Cancer stem cells (CSCs) are a small subpopulation of cancer cells with capabilities of self-renewal, differentiation, and tumorigenicity, and play a critical role in driving tumor heterogeneity that evolves insensitivity to therapeutics. For these reasons, extensive efforts have been made to identify and target CSCs to potentially improve the antitumor efficacy of therapeutics. While progress has
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Computational and artificial intelligence-based approaches for drug metabolism and transport prediction Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-09 Balint Dudas, Maria A. Miteva
Drug metabolism and transport, orchestrated by drug-metabolizing enzymes (DMEs) and drug transporters (DTs), are implicated in drug–drug interactions (DDIs) and adverse drug reactions (ADRs). Reliable and precise predictions of DDIs and ADRs are critical in the early stages of drug development to reduce the rate of drug candidate failure. A variety of experimental and computational technologies have
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PPAR agonists for the treatment of neuroinflammatory diseases Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-12-07 Celene Titus, Md Tozammel Hoque, Reina Bendayan
Peroxisome proliferator-activated receptors [PPARs; PPARα, PPARβ/δ (also known as PPARδ), and PPARγ] widely recognized for their important role in glucose/lipid homeostasis, have recently received significant attention due to their additional anti-inflammatory and neuroprotective effects. Several newly developed PPAR agonists have shown high selectivity for specific PPAR isoforms and , offering the
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Advisory Board and Contents Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-11-16
Abstract not available
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Targeting sensory neuron GPCRs for peripheral neuropathic pain Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-11-11 Ankit Uniyal, Vinod Tiwari, Takashi Tsukamoto, Xinzhong Dong, Yun Guan, Srinivasa N. Raja
Despite the high prevalence of peripheral neuropathic pain (NP) conditions and significant progress in understanding its underlying mechanisms, the management of peripheral NP remains inadequate. Existing pharmacotherapies for NP act primarily on the central nervous system (CNS) and are often associated with CNS-related adverse effects, limiting their clinical effectiveness. Mounting preclinical evidence
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Subscription and Copyright Information Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-11-16
Abstract not available
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A quick guide to networking for scientists Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-11-13 Heather K. Beasley, Ky’Era V. Actkins, Andrea G. Marshall, Edgar Garza-Lopez, Celestine Wanjalla, Estevão Scudese, Annet Kirabo, Kaihua Liu, Antentor Hinton Jr
Networking is an important skill for finding social relationships relevant to one’s career. However, networking can be difficult to navigate as different social situations and career levels require unique skill sets. Here, we provide tips for effective networking at conferences, dinners, and other events.
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Cancer drug repurposing in autism spectrum disorder Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-11-06 Giorgia Pedini, Chin-Lin Chen, Tilmann Achsel, Claudia Bagni
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with uncertain origins. Understanding of the mechanisms underlying ASD remains limited, and treatments are lacking. Genetic diversity complicates drug development. Given the complexity and severity of ASD symptoms and the rising number of diagnoses, exploring novel therapeutic strategies is essential. Here, we focus on shared
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Ligand selectivity hotspots in serotonin GPCRs Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-31 Icaro A. Simon, Walden E. Bjørn-Yoshimoto, Kasper Harpsøe, Stylianos Iliadis, Bo Svensson, Anders A. Jensen, David E. Gloriam
Serotonin is a neurotransmitter regulating numerous physiological processes also modulated by drugs, for example, schizophrenia, depression, migraine, and obesity. However, these drugs typically have adverse effects caused by promiscuous binding across 12 serotonin and more than 20 homologous receptors. Recently, structures of the entire serotonin receptor family uncovered molecular ligand recognition
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Emerging approaches to induce immune tolerance to therapeutic proteins Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-29 Justine C. Noel, Daniel Lagassé, Basil Golding, Zuben E. Sauna
Immunogenicity affects the safety and efficacy of therapeutic proteins. This review is focused on approaches for inducing immunological tolerance to circumvent the immunogenicity of therapeutic proteins in the clinic. The few immune tolerance strategies that are used in the clinic tend to be inefficient and expensive and typically involve global immunosuppression, putting patients at risk of infections
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Potential therapeutic targets for trauma management Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-27 Zizheng Li, Ou Qiao, Yuru Wang, Ning Li, Yanhua Gong
Despite advances in medical treatments for severe trauma, it remains a critical condition associated with high mortality. During trauma, the release of endogenous damage-associated molecular patterns (DAMPs) can induce immune dysfunction, leading to sepsis or multiple organ dysfunction syndrome (MODS). Vaccines based on specific pathogen antigens and pathogen-associated molecular patterns (PAMPs) contribute
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m6A epitranscriptomic modification in diabetic microvascular complications Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-27 Li-Chan Lin, Zhi-Yan Liu, Jing-Jing Yang, Jian-Yuan Zhao, Hui Tao
N6-methyladenosine (m6A) modifications are modulated by m6A methyltransferases, m6A demethylases, and m6A-binding proteins. The dynamic and reversible patterns of m6A modification control cell fate programming by regulating RNA splicing, translation, and decay. Emerging evidence demonstrates that m6A modification of coding and noncoding RNAs exerts crucial effects that influence the pathogenesis of
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New tricks for an old pathway: emerging Notch-based biotechnologies and therapeutics Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-25 Elliot Medina, David H. Perez, Daniel Antfolk, Vincent C. Luca
The Notch pathway regulates a diverse array of cell fate decisions, making it an enticing target in cancer therapy and regenerative medicine. During the early stages of Notch drug development, off-target toxicity precluded the approval of Notch inhibitors for the treatment of cancer. However, recent advances in our understanding of Notch structure and signaling have led to the development of several
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Glaucoma: neuroprotection with NAD-based therapeutic interventions Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-23 Alberto Chiarugi
Clinical evidence shows that intraocular hypertension is not the primary pathogenetic event of glaucoma, whereas early neurodegeneration of retinal ganglion cells (RGCs) represents a key therapeutic target. Unfortunately, failure of clinical trials with neuroprotective agents, in particular those testing the anti-excitotoxic drug memantine, generated widespread skepticism regarding the possibility
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Development of bispecific T cell engagers: harnessing quantitative systems pharmacology Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-17 Timothy Qi, Xiaozhi Liao, Yanguang Cao
Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens
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Advisory Board and Contents Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-12
Abstract not available
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Advancing targeted protein degradation modalities Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-12 Jerry C. Madukwe
Abstract not available
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Celiac disease: mechanisms and emerging therapeutics Trends Pharmacol. Sci. (IF 13.8) Pub Date : 2023-10-14 Harrison A. Besser, Chaitan Khosla
Celiac disease (CeD) is a widespread, gluten-induced, autoimmune disorder that lacks any medicinal therapy. Towards the goal of developing non-dietary treatments for CeD, research has focused on elucidating its molecular and cellular etiology. A model of pathogenesis has emerged centered on interactions between three molecular families: specific class II MHC proteins on antigen-presenting cells (APCs)