journal
https://read.qxmd.com/read/38796097/exosome-mediated-protac-delivery-for-treatment-of-rna-viral-infections-and-zoonoses
#1
JOURNAL ARTICLE
Nobendu Mukerjee, Swastika Maitra, Arabinda Ghosh, Athanasios Alexiou, Nanasaheb D Thorat
The increase in diseases caused by RNA viruses, such as influenza, severe acute respiratory syndrome-coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS), and Ebola, presents a growing global health challenge as well as the threat of zoonosis. Traditional antiviral treatments are often undermined by fast-mutating viruses, drug resistance, and newly emerging pathogens. Here, we explore proteolysis-targeting chimeras (PROTACs), a novel protein degradation machinery that has the potential to reshape the way in which RNA viral infections can be managed...
May 23, 2024: Drug Discovery Today
https://read.qxmd.com/read/38796096/healthcare-decision-making-for-tumour-agnostic-therapies-in-europe-lessons-learned
#2
REVIEW
Milou A Hogervorst, Christine C van Hattem, Gabe S Sonke, Aukje K Mantel-Teeuwisse, Wim G Goettsch, Lourens T Bloem
The tumour-agnostic authorisations of larotrectinib and entrectinib shifted the paradigm for indication setting. European healthcare decision-makers agreed on their therapeutic potential but diverged primarily in identified uncertainties concerning basket trial designs and endpoints, prognostic value of neurotrophic tropomyosin receptor kinase (NTRK) gene fusions, and resistance mechanisms. In addition, assessments of relevant comparators, unmet medical needs (UMNs), and implementation of NTRK-testing strategies diverged...
May 23, 2024: Drug Discovery Today
https://read.qxmd.com/read/38789027/the-impact-of-e3-ligase-choice-on-protac-effectiveness-in-protein-kinase-degradation
#3
REVIEW
Tomasz Sobierajski, Joanna Małolepsza, Marta Pichlakb, Edyta Gendaszewska-Darmach, Katarzyna M Błażewska
Proteolysis targeting chimera (PROTACs) provide a novel therapeutic approach that is revolutionizing drug discovery. The success of PROTACs largely depends on the combination of their three fragments: E3 ligase ligand, linker and protein of interest (POI)-targeting ligand. We summarize the pivotal significance of the precise combination of the E3 ligase ligand with the POI-recruiting warhead, which is crucial for the successful execution of cellular processes and achieving the desired outcomes. Therefore, the key to selection was the use of at least two ligands recruiting two different ligases...
May 22, 2024: Drug Discovery Today
https://read.qxmd.com/read/38762089/best-practices-for-machine-learning-in-antibody-discovery-and-development
#4
REVIEW
Leonard Wossnig, Norbert Furtmann, Andrew Buchanan, Sandeep Kumar, Victor Greiff
In the past 40 years, therapeutic antibody discovery and development have advanced considerably, with machine learning (ML) offering a promising way to speed up the process by reducing costs and the number of experiments required. Recent progress in ML-guided antibody design and development (D&D) has been hindered by the diversity of data sets and evaluation methods, which makes it difficult to conduct comparisons and assess utility. Establishing standards and guidelines will be crucial for the wider adoption of ML and the advancement of the field...
May 16, 2024: Drug Discovery Today
https://read.qxmd.com/read/38762088/all-in-one-nanotheranostic-platform-based-on-tumor-microenvironment-new-strategies-in-multimodal-imaging-and-therapeutic-protocol
#5
REVIEW
Yanchen Li, Xiaoyan Pan, Ping Hai, Yongbiao Zheng, Yuanyuan Shan, Jie Zhang
Conventional tumor diagnosis and treatment approaches have significant limitations in clinical application, whereas personalized theranostistic nanoplatforms can ensure advanced diagnosis, precise treatment, and even a good prognosis in cancer. Tumor microenvironment (TME)-targeted therapeutic strategies offer absolute advantages in all aspects compared to tumor cell-targeted therapeutic strategies. It is essential to create a TME-responsive all-in-one nanotheranostic platform to facilitate individualized tumor treatment...
May 16, 2024: Drug Discovery Today
https://read.qxmd.com/read/38762087/harnessing-the-role-of-microneedles-as-sensors-current-status-and-future-perspectives
#6
REVIEW
Molakpogu Ravindra Babu, Sukriti Vishwas, Monica Gulati, Kamal Dua, Sachin Kumar Singh
In recent years, microneedles (MNs) have been transformed to serve a wide range of applications in the biomedical field. Their role as sensors in wearable devices has provided an alternative to blood-based monitoring of health and diagnostic methods. Hence, they have become a topic of research interest for several scientists working in the biomedical field. These MNs as sensors offer the continuous monitoring of biomarkers like glucose, nucleic acids, proteins, polysaccharides and electrolyte ions, which can therefore screen for and diagnose disease conditions in humans...
May 16, 2024: Drug Discovery Today
https://read.qxmd.com/read/38762086/targeting-furin-a-cellular-proprotein-convertase-for-covid-19-prevention-and-therapeutics
#7
REVIEW
Xia Jiang, Dabing Li, Mazaher Maghsoudloo, Xinghai Zhang, Wenzhe Ma, Junjiang Fu
SARS-CoV-2 has triggered an international outbreak of the highly contagious acute respiratory disease known as COVID-19. Identifying key targets in the virus infection lifecycle is crucial for developing effective prevention and therapeutic strategies against it. Furin is a serine endoprotease that belongs to the family of proprotein convertases and plays a critical role in the entry of host cells by SARS-CoV-2. Furin can cleave a specific S1/S2 site, PRRAR, on the spike protein of SARS-CoV-2, which promotes viral transmission by facilitating membrane fusion...
May 16, 2024: Drug Discovery Today
https://read.qxmd.com/read/38762085/coupling-of-surface-plasmon-resonance-and-mass-spectrometry-for-molecular-interaction-studies-in-drug-discovery
#8
REVIEW
Yuandi Zhao, Darya Hadavi, Ingrid Dijkgraaf, Maarten Honing
Various analytical technologies have been developed for the study of target-ligand interactions. The combination of these technologies gives pivotal information on the binding mechanism, kinetics, affinity, residence time, and changes in molecular structures. Mass spectrometry (MS) offers structural information, enabling the identification and quantification of target-ligand interactions. Surface plasmon resonance (SPR) provides kinetic information on target-ligand interaction in real time. The coupling of MS and SPR complements each other in the studies of target-ligand interactions...
May 16, 2024: Drug Discovery Today
https://read.qxmd.com/read/38759949/the-importance-of-a-go-to-market-strategy-in-the-commercialisation-of-cellular-immunotherapies
#9
REVIEW
Cristina Piñel-Neparidze, Harry Bickerstaffe, Samvar Shah, Jennifer Versnel
Cellular immunotherapy (CIT) has both demonstrated outstanding levels of efficacy in cancer and presented unique commercialisation challenges. A historical analysis of go-to-market (G2M) strategies used to develop the first chimeric antigen receptor T cells (CAR-Ts) can offer insight into how companies leverage partnership or independence to ensure commercial success. Collaboration-based strategies, such as partnerships, acquisitions, and licensing deals, have predominated in the industry to maximise revenue and patient access...
May 15, 2024: Drug Discovery Today
https://read.qxmd.com/read/38759948/geometric-deep-learning-methods-and-applications-in-3d-structure-based-drug-design
#10
REVIEW
Qifeng Bai, Tingyang Xu, Junzhou Huang, Horacio Pérez-Sánchez
3D structure-based drug design (SBDD) is considered a challenging and rational way for innovative drug discovery. Geometric deep learning is a promising approach that solves the accurate model training of 3D SBDD through building neural network models to learn non-Euclidean data, such as 3D molecular graphs and manifold data. Here, we summarize geometric deep learning methods and applications that contain 3D molecular representations, equivariant graph neural networks (EGNNs), and six generative model methods [diffusion model, flow-based model, generative adversarial networks (GANs), variational autoencoder (VAE), autoregressive models, and energy-based models]...
May 15, 2024: Drug Discovery Today
https://read.qxmd.com/read/38750929/an-exploration-of-alternative-therapeutic-targets-for-aortic-disease-in-marfan-syndrome
#11
REVIEW
Lotte J F Van Den Heuvel, Silke Peeters, Josephina A N Meester, Paul J Coucke, Bart L Loeys
Marfan syndrome is a rare connective tissue disorder that causes aortic dissection-related sudden death. Current conventional treatments, beta-blockers, and type 1 angiotensin II receptor blockers are prescribed to slow down aortic aneurysm progression to delay (prophylactic) aortic surgery. However, neither of these treatments ceases aortic growth completely. This review focuses on potential alternative therapeutic leads in the field, ranging from widely used medication with beneficial effects on the aorta to experimental inhibitors with the potential to stop aortic growth in Marfan syndrome...
May 13, 2024: Drug Discovery Today
https://read.qxmd.com/read/38750928/peptide-spiders-are-emerging-as-novel-therapeutic-interventions-for-nucleic-acid-delivery
#12
REVIEW
Mahfoozur Rahman, Ankit Sahoo, Waleed H Almalki, Salem Salman Almujri, Abdulmalik Saleh Alfawaz Altamimi, Abdurrahman Alhamyani, Sohail Akhter
The FDA has approved many nucleic acid (NA)-based products. The presence of charges and biological barriers however affect stability and restrict widespread use. The emergence of three parts in one system, i.e., electrostatic complexation of peptide with PEG-NAs via nonreducible and reducible agents. The reducible linkage made detachment of siRNA from PEG easy compared with a nonreducible linkage. A peptide spider produces a small hydrodynamic particle size, which can improve drug release and pharmacokinetics...
May 13, 2024: Drug Discovery Today
https://read.qxmd.com/read/38750927/design-of-greener-drugs-aligning-parameters-in-pharmaceutical-r-d-and-drivers-for-environmental-impact
#13
REVIEW
Rodrigo Vidaurre, Irene Bramke, Neele Puhlmann, Stewart F Owen, Daniela Angst, Caroline Moermond, Bastiaan Venhuis, Anna Lombardo, Klaus Kümmerer, Tiina Sikanen, Jim Ryan, Andreas Häner, Gemma Janer, Silvio Roggo, Alison Nimrod Perkins
Active pharmaceutical ingredients (APIs) in the environment, primarily resulting from patient excretion, are of concern because of potential risks to wildlife. This has led to more restrictive regulatory policies. Here, we discuss the 'benign-by-design' approach, which encourages the development of environmentally friendly APIs that are also safe and efficacious for patients. We explore the challenges and opportunities associated with identifying chemical properties that influence the environmental impact of APIs...
May 13, 2024: Drug Discovery Today
https://read.qxmd.com/read/38740363/the-role-of-ripk1-in-chronic-obstructive-pulmonary-disease
#14
REVIEW
Aman Tiwari, Avtar Singh Gautam, Shivam Kumar Pandey, Shreya Singh, Rakesh Kumar Singh
Necroptosis has emerged as one of the crucial pathological processes involved in the regulation of cell death and inflammation in chronic obstructive pulmonary disease (COPD). Airway epithelial necroptosis is closely linked to COPD pathogenesis. Necroptotic lung cells can release damage-associated molecular patterns (DAMPs) that can initiate a robust inflammatory response. However, the underlying mechanism of necroptosis in COPD is still not clearly understood. Therefore, we aimed to explore the roles and mechanisms of receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-mediated necroptosis in the regulation of inflammatory responses in COPD to provide insights into RIPK1-inhibitor drug discovery efforts and their therapeutic benefits in COPD...
May 11, 2024: Drug Discovery Today
https://read.qxmd.com/read/38729235/impact-of-the-diseased-lung-microenvironment-on-the-in-vivo-fate-of-inhaled-particles
#15
REVIEW
Jiayi Gai, Liu Liu, Xin Zhang, Jian Guan, Shirui Mao
Inhalation drug delivery is superior for local lung disease therapy. However, there are several unique absorption barriers for inhaled drugs to overcome, including limited drug deposition at the target site, mucociliary clearance, pulmonary macrophage phagocytosis, and systemic exposure. Moreover, the respiratory disease state can affect or even destroy the physiology of the lung, thus influencing the in vivo fate of inhaled particles compared with that in healthy lungs. Nevertheless, limited information is available on this effect...
May 8, 2024: Drug Discovery Today
https://read.qxmd.com/read/38723764/the-idmp-ontology-a-catalyst-to-unleash-the-potential-of-ai-and-accelerate-data-driven-decisions-with-industry-wide-standards
#16
EDITORIAL
Sheila Elz, A G Bayer, Gerd Kleemann, Torsten Osthus, Martin Petracchi, A G Novartis, Raphael Sergent
No abstract text is available yet for this article.
May 7, 2024: Drug Discovery Today
https://read.qxmd.com/read/38723763/text-summarization-with-chatgpt-for-drug-labeling-documents
#17
JOURNAL ARTICLE
Lan Ying, Zhichao Liu, Hong Fang, Rebecca Kusko, Leihong Wu, Stephen Harris, Weida Tong
Text summarization is crucial in scientific research, drug discovery and development, regulatory review, and more. This task demands domain expertise, language proficiency, semantic prowess, and conceptual skill. The recent advent of large language models (LLMs), such as ChatGPT, offers unprecedented opportunities to automate this process. We compared ChatGPT-generated summaries with those produced by human experts using FDA drug labeling documents. The labeling contains summaries of key labeling sections, making them an ideal human benchmark to evaluate ChatGPT's summarization capabilities...
May 7, 2024: Drug Discovery Today
https://read.qxmd.com/read/38719144/making-good-decisions-in-early-drug-discovery
#18
REVIEW
Virginie Sandrin, Bigna Wörsdörfer, Sam Vardy, Ellen Coopersmith, Martin Stahl
The earliest phases of drug discovery require diverse scientific disciplines to work hand in hand to address many unknowns. Good decision making is crucial for success in this context and, yet, the topic of sound planning has rarely been addressed for the earliest stages of drug discovery. We propose a tailored, qualitative 'decision quality' process that can serve as a guide toward generating project plans optimized to address a given project situation. Furthermore, we propose a visual flow-chart format for the selected plan that includes key decisions and activities, together forming a decision roadmap of the plan...
May 6, 2024: Drug Discovery Today
https://read.qxmd.com/read/38719143/hypoxia-induced-pulmonary-hypertension-in-adults-and-newborns-implications-for-drug-development
#19
REVIEW
Abu Shufian Ishtiaq Ahmed, Arlin B Blood, Lubo Zhang
Chronic hypoxia-induced pulmonary hypertension (CHPH) presents a complex challenge, characterized by escalating pulmonary vascular resistance and remodeling, threatening both newborns and adults with right heart failure. Despite advances in understanding the pathobiology of CHPH, its molecular intricacies remain elusive, particularly because of the multifaceted nature of arterial remodeling involving the adventitia, media, and intima. Cellular imbalance arises from hypoxia-induced mitochondrial disturbances and oxidative stress, reflecting the diversity in pulmonary hypertension (PH) pathology...
May 6, 2024: Drug Discovery Today
https://read.qxmd.com/read/38705512/vaginal-drug-delivery-system-a-promising-route-of-drug-administration-for-local-and-systemic-diseases
#20
REVIEW
M Tamil Mani Subi, Selvasudha Nandhakumar, Hannah R Vasanthi
Scientists around the globe have done cutting-edge research to facilitate the delivery of poorly absorbed drugs via various routes of administration and different delivery systems. The vaginal route of administration has emerged as a promising mode of drug delivery, attributed to its anatomy and physiology. Novel drug delivery systems overcome the demerits of conventional systems via nanobiotechnology. This review will focus on the disorders associated with women that are currently targeted by vaginal drug delivery systems...
May 3, 2024: Drug Discovery Today
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