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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
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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, 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 Christopher Haynie, Spencer Gardiner, 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
Liver cancer, the sixth most common cancer globally and the second-leading cause of cancer-related deaths, presents a critical public health threat. Diagnosis often occurs in advanced stages of the disease, aligning incidence with fatality rates. Given that established treatments, such as stereotactic body radiation therapy and transarterial radioembolization, face accessibility and affordability challenges
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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
Postbiotics, the next generation of probiotics, are extracts that are free of living and nonviable bacteria and show strong modulatory effects on the gut flora. Examples include vitamin B12, vitamin K, folate, lipopolysaccharides, enzymes, and short-chain fatty acids (SCFAs), representing a subset of essential nutrients commonly found in the human diet. Postbiotics have been observed to demonstrate
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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
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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
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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
A principal challenge in the discovery of proteolysis targeting chimeras (PROTACs) as oral medications is their bioavailability. To facilitate drug design, it is therefore essential to identify the chemical space where orally bioavailable PROTACs are more likely to be situated. To this aim, we extracted structure-bioavailability insights from published data using traditional 2D descriptors, thereby
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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
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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
Alzheimer’s disease (AD) is a neurodegenerative disease that affects over 55 million patients worldwide. Most of the approved small-molecule drugs for AD have been designed to tackle a single pathological hallmark, such as cholinergic dysfunction or amyloid toxicity, and thus may not fully address the multifactorial nature of the disease. Inhibition of both cholinesterase and glycogen synthase kinase-3β
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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
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A potential novel cancer immunotherapy: Agonistic anti-CD40 antibodies Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-23 Cheng-Zhe Jian, Li Lin, Chia-Lang Hsu, Yu-Hsin Chen, Chiun Hsu, Ching-Ting Tan, Da-Liang Ou
CD40, a novel immunomodulatory cancer therapy target, is expressed by B cells, macrophages, and dendritic cells (DCs) and mediates cytotoxic T cell priming through the CD40 ligand. Some tumors show promising responses to monotherapy or combination therapy with agonistic anti-CD40 antibodies. The development of improved anti-CD40 antibodies makes CD40 activation an innovative strategy in cancer immunotherapy
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Informatic challenges and advances in illuminating the druggable proteome Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-22 Rahil Taujale, Nathan Gravel, Zhongliang Zhou, Wayland Yeung, Krystof Kochut, Natarajan Kannan
The understudied members of the druggable proteomes offer promising prospects for drug discovery efforts. While large-scale initiatives have generated valuable functional information on understudied members of the druggable gene families, translating this information into actionable knowledge for drug discovery requires specialized informatics tools and resources. Here, we review the unique informatics
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Drugging the entire human proteome: Are we there yet? Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-19 Micholas Dean Smith, L. Darryl Quarles, Omar Demerdash, Jeremy C. Smith
Each of the ∼20,000 proteins in the human proteome is a potential target for compounds that bind to it and modify its function. The 3D structures of most of these proteins are now available. Here, we discuss the prospects for using these structures to perform proteome-wide virtual HTS (VHTS). We compare physics-based (docking) and AI VHTS approaches, some of which are now being applied with large databases
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Summary and future of medicine for hereditary angioedema Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-19 Lei Ding, Meng-Jiao Zhang, Guo-Wu Rao
Hereditary angioedema (HAE) is a rare autosomal genetic disease for which there are currently nine FDA-approved drugs. This review summarizes drug treatments for HAE based on four therapeutic pathways: inhibiting the contact system, inhibiting bradykinin binding to B2 receptors, supplying missing C1 inhibitors, and inhibiting plasminogen conversion. The review generalizes the clinical use, pharmacological
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Spatial transcriptomics data and analytical methods: An updated perspective Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-18 Danishuddin, Shawez Khan, Jong Joo Kim
Spatial transcriptomics (ST) is a newly emerging field that integrates high-resolution imaging and transcriptomic data to enable the high-throughput analysis of the spatial localization of transcripts in diverse biological systems. The rapid progress in this field necessitates the development of innovative computational methods to effectively tackle the distinct challenges posed by the analysis of
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Revolutionizing viral disease treatment: Phase separation and lysosome/exosome targeting as new areas and new paradigms for antiviral drug research Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-18 Shaoqing Du, Xueping Hu, Xinyong Liu, Peng Zhan
With the advancement of globalization, our world is becoming increasingly interconnected. However, this interconnection means that once an infectious disease emerges, it can rapidly spread worldwide. Specifically, viral diseases pose a growing threat to human health. The COVID-19 pandemic has underscored the pressing need for expedited drug development to combat emerging viral diseases. Traditional
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The European Lead Factory: Results from a decade of collaborative, public–private, drug discovery programs Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-18 Herman van Vlijmen, Andrew D. Pannifer, Phil Cochrane, Daniel Basting, Volkhart M Li, Ola Engkvist, Jean-Yves Ortholand, Markus Wagener, James Duffy, Dirk Finsinger, Jeremy Davis, Steven P. van Helden, Jon S.B. de Vlieger, European Lead Factory Consortium
The European Lead Factory (ELF) is a consortium of universities and small and medium-sized enterprises (SMEs) dedicated to drug discovery, and the pharmaceutical industry. This unprecedented consortium provides high-throughput screening, triage, and hit validation, including to non-consortium members. The ELF library was created through a novel compound-sharing model between nine pharmaceutical companies
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Drug–drug co-amorphous systems: An emerging formulation strategy for poorly water-soluble drugs Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-14 Hongge Wang, Peixu Zhao, Ruilong Ma, Jirun Jia, Qiang Fu
Overcoming the poor water solubility of small-molecule drugs is a major challenge in the development of clinical pharmaceuticals. Amorphization of crystalline drugs is a highly effective strategy to improve their aqueous solubility. However, amorphous drugs are thermodynamically unstable and likely to crystallize during manufacturing and storage. Recently, drug–drug co-amorphous systems have emerged
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Communicating computational workflows in a regulatory environment Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-12 Jonathon G. Keeney, Naila Gulzar, Jack B. Baker, Ondrej Klempir, Geoffrey D. Hannigan, Danny A. Bitton, Julia M. Maritz, Charles H.S. King IV, Janisha A. Patel, Paul Duncan, Raja Mazumder
The volume of nucleic acid sequence data has exploded recently, amplifying the challenge of transforming data into meaningful information. Processing data can require an increasingly complex ecosystem of customized tools, which increases difficulty in communicating analyses in an understandable way yet is of sufficient detail to enable informed decisions or repeats. This can be of particular interest
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Data standards in drug discovery: a long way to go Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-11 Jens M. Kelm, Marc Ferrer, Martin-Immanuel Bittner, Madhu Lal-Nag
Each year, millions to trillions of data points are generated to evaluate the response of chemicals and biologicals to human cells in vitro and in vivo using various technologies and endpoints. Despite the vast amount of data available, the development process has not become significantly more efficient in recent years. Given the increasing use of more complex physiological models, which are time-consuming
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Design strategies and recent development of bioactive modulators for glutamine transporters Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-11 Xinying Cheng, Yezhi Wang, Guangyue Gong, Pei Shen, Zhiyu Li, Jinlei Bian
Glutamine transporters are integral to the metabolism of glutamine in both healthy tissues and cancerous cells, playing a pivotal role in maintaining amino acid balance, synthesizing biomolecules, and regulating redox equilibrium. Their critical functions in cellular metabolism make them promising targets for oncological therapies. Recent years have witnessed substantial progress in the field of glutamine
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Overview of the Knowledge Management Center for Illuminating the Druggable Genome Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-11 Tudor I. Oprea, Cristian Bologa, Jayme Holmes, Stephen Mathias, Vincent T. Metzger, Anna Waller, Jeremy J. Yang, Andrew R. Leach, Lars Juhl Jensen, Keith J. Kelleher, Timothy K. Sheils, Ewy Mathé, Sorin Avram, Jeremy S. Edwards
The Knowledge Management Center (KMC) for the Illuminating the Druggable Genome (IDG) project aims to aggregate, update, and articulate protein-centric data knowledge for the entire human proteome, with emphasis on the understudied proteins from the three IDG protein families. KMC collates and analyzes data from over 70 resources to compile the Target Central Resource Database (TCRD), which is the
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Illuminating function of the understudied druggable kinome Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-11 Shawn M. Gomez, Alison D. Axtman, Timothy M. Willson, Michael B. Major, Reid R. Townsend, Peter K. Sorger, Gary L. Johnson
The human kinome, with more than 500 proteins, is crucial for cell signaling and disease. Yet, about one-third of kinases lack in-depth study. The Data and Resource Generating Center for Understudied Kinases has developed multiple resources to address this challenge including creation of a heavy amino acid peptide library for parallel reaction monitoring and quantitation of protein kinase expression
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Recent discoveries of the role of histone modifications and related inhibitors in pathological cardiac hypertrophy Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-10 Ke-Jia Wu, , Chung-Hang Leung, Ning Sun, Fei Gao, Zhaoyang Chen
Pathological cardiac hypertrophy is a common response of the heart to various pathological stimuli. In recent years, various histone modifications, including acetylation, methylation, phosphorylation and ubiquitination, have been identified to have crucial roles in regulating chromatin remodeling and cardiac hypertrophy. Novel drugs targeting these epigenetic changes have emerged as potential treatments
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Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer Drug. Discov. Today (IF 7.4) Pub Date : 2024-01-03 , Jin-jing Zhang, Yue-ping Xu, Min-min Shao, Meng-chuan Wang
N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have
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Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges Drug. Discov. Today (IF 7.4) Pub Date : 2023-12-26 Wenzhan Yang, Sugandha Saboo, Liping Zhou, Sean Askin, Annette Bak
PROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin–proteasome system. Herein, we present an analysis on
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Increased contribution of small companies to late-entry drugs: a changing trend in FDA-approved drugs during the 2020s Drug. Discov. Today (IF 7.4) Pub Date : 2023-12-23 Ryo Okuyama
Small- and medium-sized enterprises (SMEs) have significantly boosted innovative drug discovery, whereas large pharmaceutical companies have focused on incremental drug innovation. I explored the evolving role of SMEs in late-entry drug discovery. A comparative analysis of new drugs approved by the US Food and Drug Administration (FDA) during the 2020s with those approved previously revealed that SMEs
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Mapping the evolution of inhaled drug delivery research: Trends, collaborations, and emerging frontiers Drug. Discov. Today (IF 7.4) Pub Date : 2023-12-21 Xinyuan Li, Zhengxing Su, Chunyou Wang, Wen Wu, Yan Zhang, Chenhui Wang
Inhaled drug delivery is a unique administration route known for its ability to directly target pulmonary or brain regions, facilitating rapid onset and circumventing the hepatic first-pass effect. To characterize current global trends and provide a visual overview of the latest trends in inhaled drug delivery research, bibliometric analysis of data acquired from the Web of Science Core Collection
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Recent advances in dual-drug co-amorphous systems Drug. Discov. Today (IF 7.4) Pub Date : 2023-12-21 Rutuja Shelke, Varalakshmi Velagacherla, Usha Yogendra Nayak
Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including
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Human carnosinases: A brief history, medicinal relevance, and in silico analyses Drug. Discov. Today (IF 7.4) Pub Date : 2023-12-19 Klaudia Chmielewska, Serena Vittorio, Silvia Gervasoni, Krystyna Dzierzbicka, Iwona Inkielewicz-Stepniak, Giulio Vistoli