Showing papers in "Trends in Pharmacological Sciences in 2022"

TL;DR: In this article , causal, multi-target signaling modules are defined to explain disease phenotypes and their respective comorbidities, and effective therapeutic intervention is achieved by synergistic multicompound network pharmacology and drug repurposing.

TL;DR: The nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome has emerged as a key mediator of pathological inflammation in many diseases and is an exciting drug target as discussed by the authors .

TL;DR: Aquaporins facilitate the passive transport of water, solutes, or ions across biological membranes as discussed by the authors and are implicated in diverse pathologies including brain edema following stroke or trauma, epilepsy, cancer cell migration and tumor angiogenesis, metabolic disorders, and inflammation.

TL;DR: In this article , the authors discuss recent studies that have provided structure-function insights and identified regulatory surfaces that control BAX activation, and emphasize the development of small molecule orthosteric, allosteric and oligomerization modulators that provide novel opportunities for biological investigation and progress towards drugging BAX.

TL;DR: Progranulin (PGRN) encoded by the GRN gene plays a key role in the development, survival, function, and maintenance of neurons and microglia in the mammalian brain this paper .

TL;DR: An overview on currently available anti-HIV drugs and the latest developments in antiretroviral therapy can be found in this paper , where the authors provide an overview of the most recent developments in antiviral therapy.

TL;DR: In this article , the authors summarize these advances, their limitations, and suggest future areas of study necessary to bring CTC analysis to clinics, as well as suggest future research areas for CTC enumeration, characterization, and expansion to provide personalized cancer treatment.

TL;DR: High-power screening (HPS) as mentioned in this paper has been proposed for drug discovery in the context of DNA-encoded libraries, which have several orders of magnitude more screening power than HTS.

TL;DR: Microglia, brain resident immune cells, modulate development, activity, and plasticity of the central nervous system as discussed by the authors , and they emerge as strong contenders for novel neurotherapies, shifting away from merely attenuation of excessive microglial inflammatory and phagocytic activities.

TL;DR: In this article , the authors summarize the latest progress in rationally engineered variants of Escherichia coli Nissle 1917 (EcN) for the treatment of infectious diseases, metabolic disorders, and inflammatory bowel diseases.

TL;DR: In this article , the authors propose that natural long noncoding RNAs (lncRNA) structures can be explored and exploited for the rational design and assembly of synthetic RNA therapies, from which they can anticipate the pharmacological properties of lncRNA therapies that have not yet otherwise entered clinical trials.

TL;DR: In this article , the role of endoplasmic reticulum (ER) stress and the ER stress response in the onset and development of obesity was discussed, with a view to identifying novel therapeutic strategies for obesity prevention and management.

TL;DR: Pseudouridine (Ψ) is the most abundant post-transcriptional RNA modification and is widespread in multiple RNA species as discussed by the authors , which contributes to a variety of human diseases, including cancer and genetic disorders.

TL;DR: In this paper , a review delineates the evolution of the compstatin family from its academic origins to the clinic and highlights current and potential future applications of this promising drug class in complement diseases.

TL;DR: In this paper , the 3D structures of all 15 members of the B1 G protein-coupled receptors (GPCRs) have been determined at the near-atomic level.

TL;DR: In this article , the authors discuss CRISPR-Cas systems that advance both conventional and emerging therapeutics, and discuss the controls that inhibit or degrade Cas9, biomolecule-Cas9 conjugates, and base editors.

TL;DR: In this paper , a patient-centered, bottom-up workflow is proposed to guide pre-clinical development of intra-articular DMOAD therapies for OA heterogeneity, which can help in fully overcoming these barriers.

TL;DR: In this article , small extracellular vesicles (sEVs) were used to target AMP-activated protein kinase (AMPK) within the hypothalamus.

TL;DR: A review of CB2 ligand development and progress in optimising physicochemical properties, understanding advanced molecular pharmacology such as functional selectivity, and clinical evaluation for CB2-targeting compounds can be found in this paper .

TL;DR: Xu et al. as mentioned in this paper reviewed the current preclinical utility and translation potential of traditional [apolipoprotein E (APOE)- and low-density lipoprotein (LDL) receptor (LDLR)-deficient mice and emerging mouse models that include partial carotid ligation and AAV8-Pcsk9-D377Y injection in atherosclerosis research and drug discovery.

TL;DR: The potential impact of phase separation on drug discovery and RNA therapeutics, leveraging concrete examples, towards novel clinical opportunities was discussed in this paper . But, the authors did not consider the role of the condensates in the phase separation process.

TL;DR: A review of the current understanding of RNA-processing events and their role in gene regulation, with a focus on the therapeutic opportunities that have emerged within this landscape is provided in this article .

TL;DR: In this article , the role of the adenosine system in driving the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution is discussed.

TL;DR: In this article , the authors summarized recent developments in preclinical studies using various high-affinity mutagenesis and Fc fusion approaches to achieve therapeutic efficacy of recombinant soluble ACE2 decoy receptor against coronaviruses.

TL;DR: Inclisiran as discussed by the authors is a double-stranded siRNA with a triantennary Nacetylgalactosamine (GalNAc) ligand to enable targeting of hepatocytes via the asialoglycoprotein receptor (ASGPR).

TL;DR: In this paper , the authors discuss barriers for translational development of cGAS-STING activators (DNA damaging drugs and STING agonists) and recent advances of NDDS for these agents in tumor immunotherapy.

TL;DR: A review of APOBEC3 enzymes with an eye towards their potential for small-molecule discovery efforts can be found in this paper , with the focus on the potential to improve the durability of current drug therapies that are prone to resistance mutations.

TL;DR: Ritskes-Hoitinga et al. as mentioned in this paper reviewed recent progress and breakthroughs in the automation and high-throughput imaging of 3D culture models, which can be integrated with machine-learning (ML) tools to aid quantitative high throughput drug screening.

TL;DR: In this paper , the role of mitochondrial quality control in the pathogenesis of DOX cardiotoxicity was investigated and promising therapeutic approaches targeting these mechanisms were explored to aid clinical management.

TL;DR: The potential role of complement in neurodegenerative diseases has been discussed in this paper , where the authors present evidence implicating complement as a driver of pathology across these diverse diseases.