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The present state and challenges of active learning in drug discovery Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-18 Lei Wang, Zhenran Zhou, Xixi Yang, Shaohua Shi, Xiangxiang Zeng, Dongsheng Cao
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TPP-based conjugates: potential targeting ligands Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-18 Sanya Batheja, Shruti Gupta, Kiran Kumar Tejavath, Umesh Gupta
Mitochondria are one of the major sources of energy for, as well as regulators of, cancer cell metabolism. Thus, they are potential targets for the effective treatment and management of cancer. Research has explored triphenylphosphonium (TPP) derivatives as potent cancer-targeting ligands because of their lipophilic nature and mitochondrial affinity. In this review, we summarize the utility of TPP-based
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SETDB1, an H3K9-specific methyltransferase: An attractive epigenetic target to combat cancer Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-16 Seema Prashanth, Radhika Radha Maniswami, Gurukumari Rajajeyabalachandran, Sooriya Kumar Jegatheesan
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Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-16 Jingyuan Dai, Milad Ashrafizadeh, Amir Reza Aref, Gautam Sethi, Yavuz Nuri Ertas
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The emerging role of fatty acid binding protein 7 (FABP7) in cancers Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-12 William George Warren, Myles Osborn, Andrew Yates, Saoirse E. O’Sullivan
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Multi-level bioinformatics resources support drug target discovery of protein–protein interactions Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-10 Jia-Xin Liu, Xiao Zhang, Yuan-Qin Huang, Ge-Fei Hao, Guang-Fu Yang
Drug discovery often begins with a new target. Protein–protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs
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Artificial intelligence (AI) and alternative variables (AV) in drug discovery: A promising alliance Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-09 Celerino Abad-Zapatero
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General aspects of powder rheology applied to pharmaceutical formulations Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-04 Marcos Mariano
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DDR1-targeted therapies: current limitations and future potential Drug. Discov. Today (IF 7.4) Pub Date : 2024-04-04 Donglin Wu, Zihui Ding, Tao Lu, Yadong Chen, Feng Zhang, Shuai Lu
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Immunotherapy: An emerging treatment option for neurodegenerative diseases Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-29 Abhiyanta Mukherjee, Soumojit Biswas, Ipsita Roy
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The role of venom proteomics and single-domain antibodies for antivenoms: Progress in snake envenoming treatment Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-29 Anna Carolina Machado Marinho, Alexander Chapeaurouge, Brunheld Maia Dutra, Barbara Cibelle S.F. Quintela, Soraya S. Pereira, Carla Freire C. Fernandes
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2023 in review: FDA approvals of new medicines Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-27 Michael S Kinch, Zachary Kraft, Tyler Schwartz
An analysis of all new entities approved by both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) identified the approval of 69 new entities in the year 2023, 50 % more than in the previous year. Oncology drugs tied with congenital and infectious diseases drugs for the most approvals. Although orphan and priority approvals continued at a
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Enzyme-responsive design combined with photodynamic therapy for cancer treatment Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-27 Siying Zhi, Meixin Huang, Kui Cheng
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Physical and mechanical properties of ocular thin films: a systematic review and meta-analysis Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-27 Mitra Farahmandnejad, Shohreh Alipour, Ali Nokhodchi
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Tuberculosis treatment-shortening Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-26 Vinayak Singh
Tuberculosis (TB) presents a significant global health concern, with ∼10 million people developing TB and 1.3 million people dying from the disease each year. The standard treatment regimen for drug-susceptible TB was between 6 and 9 months until recently, presenting a prolonged therapeutic duration compared with other infectious diseases. This is a long time for patients to adhere to the medication
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Design, development, and technical considerations for dry powder inhaler devices Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-24 Sagar Dhoble, Archana Kapse, Vaibhav Ghegade, Manasi Chogale, Vinod Ghodake, Vandana Patravale, Lalitkumar K. Vora
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Small molecules targeting canonical transient receptor potential channels: an update Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-20 Hua Liu, Min Fu, Yifan Zhang, Qidong You, Lei Wang
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Peptide-derived ligands for the discovery of safer opioid analgesics Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-20 Abbe Eliasof, Lee-Yuan Liu-Chen, Yangmei Li
Drugs targeting the μ-opioid receptor (MOR) remain the most efficacious analgesics for the treatment of pain, but activation of MOR with current opioid analgesics also produces harmful side effects, notably physical dependence, addiction, and respiratory depression. Opioid peptides have been accepted as promising candidates for the development of safer and more efficacious analgesics. To develop peptide-based
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Best practices for managing and disseminating resources and outreach and evaluating the impact of the IDG Consortium Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-18 Dušica Vidović, Anna Waller, Jayme Holmes, Larry A. Sklar, Stephan C. Schürer
The Illuminating the Druggable Genome (IDG) consortium generated reagents, biological model systems, data, informatic databases, and computational tools. The Resource Dissemination and Outreach Center (RDOC) played a central administrative role, organized internal meetings, fostered collaboration, and coordinated consortium-wide efforts. The RDOC developed and deployed a Resource Management System
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Accelerating drug development at Bristol Myers Squibb through innovation Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-18 Kalyanee Viraswami-Appanna, Joan Buenconsejo, Charlotte Baidoo, Ivan Chan, Daniel Li, Mariann Micsinai-Balan, Ram Tiwari, Ling Yang, Venkat Sethuraman
This paper focuses on the use of novel technologies and innovative trial designs to accelerate evidence generation and increase pharmaceutical Research and Development (R&D) productivity, at Bristol Myers Squibb. We summarize learnings with case examples, on how we prepared and continuously evolved to address the increasing cost, complexities, and external pressures in drug development, to bring innovative
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Rare diseases and pyruvate kinase M2: a promising therapeutic connection Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-15 Saumya Kapoor, Vaishnavi Kalmegh, Hemant Kumar, Amit Mandoli, Amit Shard
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Master protocols and other innovative trial designs in inflammation and immunology to expedite clinical drug development Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-08 Elena Peeva, Anindita Banerjee, Christopher Banfield, Koshika Soma, Jared Christensen, Sandeep Menon, Michael S. Vincent, Mikael Dolsten
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Transitioning biomedical research toward human-centric methodologies: systems-based strategies Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-08 Helder Constantino, Francesca Pistollato, Troy Seidle
Human-centric methodologies like microphysiological systems and methods have shown promise in addressing the limitations of animal models in understanding human biology and responding to public health priorities. However, the prevailing paradigm based on animal research persists. The article proposes a systemic thinking approach, endorsed by the OECD and the EU, as a tool to leverage innovation to
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Transfer learning empowers accurate pharmacokinetics prediction of small samples Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-08 Wenbo Guo, Yawen Dong, Ge-Fei Hao
Accurate assessment of pharmacokinetic (PK) properties is crucial for selecting optimal candidates and avoiding downstream failures. Transfer learning is an innovative machine learning approach enabling high-throughput prediction with limited data. Recently, transfer learning methods showed promise in predicting ADME/PK parameters. Given the prolific growth of research on transfer learning for PK prediction
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Augmenting DMTA using predictive AI modelling at AstraZeneca Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-08 Gian Marco Ghiandoni, Emma Evertsson, David J. Riley, Christian Tyrchan, Prakash Chandra Rathi
Design-Make-Test-Analyse (DMTA) is the discovery cycle through which molecules are designed, synthesised, and assayed to produce data that in turn are analysed to inform the next iteration. The process is repeated until viable drug candidates are identified, often requiring many cycles before reaching a sweet spot. The advent of artificial intelligence (AI) and cloud computing presents an opportunity
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Rise of the Allotrope Simple Model: Update from 2023 Fall Allotrope Connect Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-08 Spencer Gardiner, Christopher Haynie, Dennis Della Corte
The Allotrope Foundation (AF) started as a group of pharmaceutical companies, instrument, and software vendors that set out to simplify the exchange of data in the laboratory. After a decade of work, they released products that have found adoption in various companies. Most recently, the Allotrope Simple Model (ASM) was developed to speed up and widen the adoption. As a result, the Foundation has recently
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Treating liver cancer through arginine depletion Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-06 Yenisetti Rajendra Prasad, J. Anakha, Abhay H. Pande
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Small molecule drug metabolite synthesis and identification: why, when and how? Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-05 Julia Shanu-Wilson, Samuel Coe, Liam Evans, Jonathan Steele, Stephen Wrigley
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Is calcitonin gene-related peptide (CGRP) the missing link in food histamine-induced migraine? A review of functional gut-to-trigeminovascular system connections Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-05 Fernando de Mora, Karl Messlinger
Calcitonin gene-related peptide (CGRP) and histamine plasma concentrations increase during migraine attacks. Both mediators are potent vasodilators, and they have been shown to reciprocally contribute to the release of each other in the trigeminovascular system, possibly driving migraine development. A high-histamine-content diet triggers migraine in patients who have histamine degradation deficiency
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New approaches for challenging therapeutic targets Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-05 Karlie R. Sharma, Abir Malik, Rebecca A. Roof, Jim P. Boyce, Sharad K. Verma
Despite successes with new drug approvals over the past two decades through conventional drug development approaches, many human diseases remain intractable to current therapeutic interventions. Possible barriers may be that the complexity of the target, and disease biology, are impervious to such conventional drug development approaches. The US National Institutes of Health hosted a workshop with
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Generation of a drug-induced renal injury list to facilitate the development of new approach methodologies for nephrotoxicity Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-01 Skylar Connor, Ting Li, Yanyan Qu, Ruth A Roberts, Weida Tong
Drug-induced renal injury (DIRI) causes >1.5 million adverse events annually in the USA alone. Although standard biomarkers exist for DIRI, they lack the sensitivity or specificity to detect nephrotoxicity before the significant loss of renal function. In this study, we describe the creation of DIRIL – a list of drugs associated with DIRI and nephrotoxicity – from two literature datasets with DIRI
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Making more of less: using divestitures to unlock pharmaceutical innovation Drug. Discov. Today (IF 7.4) Pub Date : 2024-03-01 Killian J. McCarthy, Rick (H.L) Aalbers
Pharmaceutical managers have been encouraged to look to acquisitions and alliances for innovation. However, the literature warns that the capacity of a company to ‘absorb’ new knowledge is limited. Here, we introduce corporate divestitures as a tool for freeing up managerial attention. We build a sample of 349 companies, which announced 1784 divestitures and filed 63523 patents, over a 15-year period
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Advancing pharmacogenetics research in Africa: the “Project Africa GRADIENT” initiative Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-29 Carene Anne Alene Ndong Sima, Houcemeddine Othman, Marlo Möller, The Project Africa GRADIENT Consortium
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Microfluidics for personalized drug delivery Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-29 Seyed Ebrahim Alavi, Sitah Alharthi, Seyedeh Fatemeh Alavi, Seyed Zeinab Alavi, Gull E. Zahra, Aun Raza, Hasan Ebrahimi Shahmabadi
This review highlights the transformative impact of microfluidic technology on personalized drug delivery. Microfluidics addresses issues in traditional drug synthesis, providing precise control and scalability in nanoparticle fabrication, and microfluidic platforms show high potential for versatility, offering patient-specific dosing and real-time monitoring capabilities, all integrated into wearable
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A call to rethink the necessity of and challenges facing academic research organizations in the new era of drug innovation in China Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-23 Huiyao Huang, Ning Jiang, Wenting Chen, Yu Tang, Ning Li
The objectives of drug R&D in China have shifted toward innovation and globalization, highlighting the ecological imperative to involve innovative partner-like academic research organizations (AROs). AROs are led by academic institutions and, when compared to contract research organizations (CROs), their strengths lie in promoting academic excellence, knowledge sharing, independence, collaborative
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A drug delivery strategy emerges that has the potential to transform cancer therapy Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-23 Nigel Theobald, David Templeton
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Recent advances in 3D bioprinting for cancer research: From precision models to personalized therapies Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-22 Ruchika, Neha Bhardwaj, Sudesh Kumar Yadav, Ankit Saneja
Cancer remains one of the most devastating diseases, necessitating innovative and precise therapeutic solutions. The emergence of 3D bioprinting has revolutionized the platform of cancer therapy by offering bespoke solutions for drug screening, tumor modeling, and personalized medicine. The utilization of 3D bioprinting enables the fabrication of complex tumor models that closely mimic the microenvironment
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Orphan GPR52 as an emerging neurotherapeutic target Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-20 Saghir Ali, Pingyuan Wang, Ryan E. Murphy, John A. Allen, Jia Zhou
GPR52 is a highly conserved, brain-enriched, G-coupled orphan G protein-coupled receptor (GPCR) that controls various cyclic AMP (cAMP)-dependent physiological and pathological processes. Stimulation of GPR52 activity might be beneficial for the treatment of schizophrenia, psychiatric disorders and other human neurological diseases, whereas inhibition of its activity might provide a potential therapeutic
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Potential of postbiotics for the treatment of metabolic disorders Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-20 Neeraj Mishra, Ashish Garg, Sumel Ashique, Shvetank Bhatt
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Ferroptosis as a potential therapeutic target for age-related macular degeneration Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-17 Dongcheng Liu, Ziling Liu, Hongxia Liao, Zhe-Sheng Chen, Bo Qin
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Gen AI’s real opportunity in drug development? As a smart, strategic decision aid Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-15 D, a, n, i, e, l, , J, a, m, i, e, s, o, n
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Context is everything in regulatory application of large language models (LLMs) Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-15 Weida Tong, Michael Renaudin, GCRSR Interagency LLMs Taskforce
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Unveiling the impacts of FDA Breakthrough Therapy Designation: a dual-perspective examination of economic and developmental outcomes for biotechnology companies Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-15 Joab Williamson, Alexander James Spicer, Elina Louramo, Juho Jalkanen
Biotechnology and small pharma companies must recognize the opportunity presented by FDA Breakthrough Therapy Designation (BTD) to expedite drug development for serious conditions. This paper evaluates BTD economic and developmental impacts on such companies. Analysis of 29 BTD events from 2017 to 2022 revealed immediate share price boosts and improved drug approval rates, alongside faster development
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Exploring the chemical space of orally bioavailable PROTACs Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-14 Giulia Apprato, Vasanthanathan Poongavanam, Diego Garcia Jimenez, Yoseph Atilaw, Mate Erdelyi, Giuseppe Ermondi, Giulia Caron, Jan Kihlberg
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Academic drug discovery: Challenges and opportunities Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-14 Angela J. Murray, Liam R. Cox, Holly V. Adcock, Ruth A. Roberts
There are many different approaches to drug discovery in academia, some of which are based broadly on the industrial model of discovering novel targets and then conducting screening within academic drug discovery centres to identify hit molecules. Here we describe our approach to drug discovery, which makes more efficient use of the capabilities and resources of the different stakeholders. Specifically
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Recent trends in targeted delivery of smart nanocarrier-based microbial enzymes for therapeutic applications Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-09 Nikita Jangra, Anubhuti Kawatra, Bharti Datten, Shefali Gupta, Pooja Gulati
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Nanocrystal technologies in biomedical science: From the bench to the clinic Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-08 Ekta Pardhi, Ravindra Vasave, Vaibhavi Srivastava, Rati Yadav, Neelesh Kumar Mehra
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Dual-target inhibitors of cholinesterase and GSK-3β to modulate Alzheimer’s disease Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-08 Junqiu He, Kin Yip Tam
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Can drug production be democratized? Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-07 G, e, n, n, a, r, o, , D, ', U, r, s, o
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Cost-effectiveness comparison between blood biomarkers and conventional tests in Alzheimer's disease diagnosis Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-02 Kenta Noda, Yeongjoo Lim, Rei Goto, Shintaro Sengoku, Kota Kodama
Dementia management has evolved with drugs such as lecanemab, shifting management from palliative care to early diagnosis and intervention. However, the administration of these drugs presents challenges owing to the invasiveness, high cost and limited availability of amyloid-PET and cerebrospinal fluid tests for guiding drug administration. Our manuscript explores the potential of less invasive blood
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Recently reported cell migration inhibitors: Opportunities and challenges for antimetastatic agents Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-02 Samuel K. Akompong, Yang Li, Wenxue Gong, Long Ye, Jinping Liu
Antimetastatic agents are highly desirable for cancer treatment because of the severe medical challenges and high mortality resulting from tumor metastasis. Having demonstrated antimetastatic effects in numerous and studies, migration inhibitors present significant opportunities for developing a new class of anticancer drugs. To provide a useful overview on the latest research in migration inhibitors
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Artificial intelligence in drug discovery: A new frontier in the fight against Mycobacterium tuberculosis Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-01 Mohammad Abavisani, Alireza khoshrou, Amirhossein Sahebkar
Abstract not available
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NAFLD and NASH: etiology, targets and emerging therapies Drug. Discov. Today (IF 7.4) Pub Date : 2024-02-01 Shulin Wei, Li Wang, Paul C. Evans, Suowen Xu
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) pose a significant threat to human health and cause a tremendous socioeconomic burden. Currently, the molecular mechanisms of NAFLD and NASH remain incompletely understood, and no effective pharmacotherapies have been approved. In the past five years, significant advances have been achieved in our understanding of the
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Innovative strategies for measuring kinase activity to accelerate the next wave of novel kinase inhibitors Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-30 Tim S. Veth, Nynke M. Kannegieter, Erik L. de Graaf, Rob Ruijtenbeek, Jos Joore, Anna Ressa, Maarten Altelaar
The development of protein kinase inhibitors (PKIs) has gained significance owing to their therapeutic potential for diseases like cancer. In addition, there has been a rise in refining kinase activity assays, each possessing unique biological and analytical characteristics crucial for PKI development. However, the PKI development pipeline experiences high attrition rates and approved PKIs exhibit
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Structural–functional analysis of drug target aspartate semialdehyde dehydrogenase Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-30 Rajender Kumar, Rajkumar R, Vineet Diwakar, Nazam Khan, Gautam Kumar Meghwanshi, Prabha Garg
Aspartate β-semialdehyde dehydrogenase (ASADH) is a key enzyme in the biosynthesis of essential amino acids in microorganisms and some plants. Inhibition of ASADHs can be a potential drug target for developing novel antimicrobial and herbicidal compounds. This review covers up-to-date information about sequence diversity, ligand/inhibitor-bound 3D structures, potential inhibitors, and key pharmacophoric
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Nanomedicines as enhancers of tumor immunogenicity to augment cancer immunotherapy Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-29 Gaidaa M. Dogheim, Nourhan E. El Feel, Esraa A. Abd El-Maksod, Sandra Sh. Amer, Sanaa A. El-Gizawy, Ahmed S. Abd Elhamid, Ahmed O. Elzoghby
The potential of cancer immunotherapy is hampered by the poor immunogenicity of cancer cells. Strategies to enhance tumor immunogenicity are imperative to enhance T cell-mediated anti-tumor immunity. Although conventional therapeutics can increase tumor antigen expression or stimulate the release of danger signals to promote immunogenic cell death (ICD), they face challenges relating to efficacy and
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Recent advances in multitarget-directed ligands via in silico drug discovery Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-26 Krishnaiah Maddeboina, Bharath Yada, Shikha Kumari, Cody McHale, Dhananjaya Pal, Donald L. Durden
To combat multifactorial refractory diseases, such as cancer, cardiovascular, and neurodegenerative diseases, multitarget drugs have become an emerging area of research aimed at ‘synthetic lethality’ (SL) relationships associated with drug-resistance mechanisms. In this review, we discuss the design of dual and triple-targeted ligands, strategies by which specific ‘warhead’ groups are incorporated
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Recent advances in bioaffinity strategies for preclinical and clinical drug discovery: Screening natural products, small molecules and antibodies Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-24 Haochun Jin, Dianxin Cui, Yu Fan, Guodong Li, Zhangfeng Zhong, Yitao Wang
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Nanoformulations of chemotherapeutic activators of the cGAS–STING pathway in tumor chemoimmunotherapy Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-24 Lingzhi Wang, Zhuo Yu, Jihong Zhang, Jianfeng Guo
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Druggable genome special issue: An introduction Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-24 K, a, r, l, i, e, , R, ., , S, h, a, r, m, a
Abstract not available