Artificial intelligence in drug discovery: A new frontier in the fight against Mycobacterium tuberculosis
Drug Discov Today. 2024 Feb 1;29(3):103909. doi: 10.1016/j.drudis.2024.103909. Online ahead of print.NO ABSTRACTPMID:38307380 | DOI:10.1016/j.drudis.2024.103909 (Source: Drug Discovery Today)
Source: Drug Discovery Today - February 2, 2024 Category: Drugs & Pharmacology Authors: Mohammad Abavisani Alireza Khoshrou Amirhossein Sahebkar Source Type: research
NAFLD and NASH: etiology, targets and emerging therapies
Drug Discov Today. 2024 Feb 1;29(3):103910. doi: 10.1016/j.drudis.2024.103910. Online ahead of print.ABSTRACTNon-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 pathomechanisms and potential pharmacotherapies of NAFLD and NASH. Research advances include the investigation of the ...
Source: Drug Discovery Today - February 1, 2024 Category: Drugs & Pharmacology Authors: Shulin Wei Li Wang Paul C Evans Suowen Xu Source Type: research
Innovative strategies for measuring kinase activity to accelerate the next wave of novel kinase inhibitors
Drug Discov Today. 2024 Jan 30;29(3):103907. doi: 10.1016/j.drudis.2024.103907. Online ahead of print.ABSTRACTThe 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 unexploited potential because of variable patient responses. Enhancing PKI development efficiency involves addressing c...
Source: Drug Discovery Today - February 1, 2024 Category: Drugs & Pharmacology Authors: Tim S Veth Nynke M Kannegieter Erik L de Graaf Rob Ruijtenbeek Jos Joore Anna Ressa Maarten Altelaar Source Type: research
Structural-functional analysis of drug target aspartate semialdehyde dehydrogenase
Drug Discov Today. 2024 Jan 30;29(3):103908. doi: 10.1016/j.drudis.2024.103908. Online ahead of print.ABSTRACTAspartate 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 features of ASADH useful in designing novel and target-specific inhibitors of ASADH. Most reported ASADH inhibit...
Source: Drug Discovery Today - February 1, 2024 Category: Drugs & Pharmacology Authors: Rajender Kumar Rajkumar R Vineet Diwakar Nazam Khan Gautam Kumar Meghwanshi Prabha Garg Source Type: research
Nanomedicines as enhancers of tumor immunogenicity to augment cancer immunotherapy
Drug Discov Today. 2024 Jan 29;29(3):103905. doi: 10.1016/j.drudis.2024.103905. Online ahead of print.ABSTRACTThe 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 tumor-specific delivery. Nanomedicines can efficiently deliver tumor antigens, immune adjuvants, epigenetic modulator...
Source: Drug Discovery Today - January 31, 2024 Category: Drugs & Pharmacology Authors: 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 Source Type: research
Recent advances in multitarget-directed ligands via in silico drug discovery
Drug Discov Today. 2024 Jan 26;29(3):103904. doi: 10.1016/j.drudis.2024.103904. Online ahead of print.ABSTRACTTo 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 in silico design of dual and triple-targeted ligands, strategies by which specific 'warhead' groups are incorporated into a parent compound or scaffold with primary inhibitory activity against one target to develop one small m...
Source: Drug Discovery Today - January 27, 2024 Category: Drugs & Pharmacology Authors: Krishnaiah Maddeboina Bharath Yada Shikha Kumari Cody McHale Dhananjaya Pal Donald L Durden Source Type: research
Recent advances in bioaffinity strategies for preclinical and clinical drug discovery: Screening natural products, small molecules and antibodies
Drug Discov Today. 2024 Jan 24;29(3):103885. doi: 10.1016/j.drudis.2024.103885. Online ahead of print.ABSTRACTBioaffinity drug screening strategies have gained popularity in preclinical and clinical drug discovery for natural products, small molecules and antibodies owing to their superior selectivity, the large number of compounds to be screened and their ability to minimize the time and expenses of the drug discovery process. This paper provides a systematic summary of the principles of commonly used bioaffinity-based screening methods, elaborates on the success of bioaffinity in clinical drug development and summarizes ...
Source: Drug Discovery Today - January 26, 2024 Category: Drugs & Pharmacology Authors: Haochun Jin Dianxin Cui Yu Fan Guodong Li Zhangfeng Zhong Yitao Wang Source Type: research
Druggable genome special issue: An introduction
Drug Discov Today. 2024 Jan 24;29(3):103887. doi: 10.1016/j.drudis.2024.103887. Online ahead of print.NO ABSTRACTPMID:38278477 | DOI:10.1016/j.drudis.2024.103887 (Source: Drug Discovery Today)
Source: Drug Discovery Today - January 26, 2024 Category: Drugs & Pharmacology Authors: Karlie R Sharma Source Type: research
A potential novel cancer immunotherapy: Agonistic anti-CD40 antibodies
Drug Discov Today. 2024 Jan 23;29(3):103893. doi: 10.1016/j.drudis.2024.103893. Online ahead of print.ABSTRACTCD40, 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. In this review, we trace the history of CD40 research and summarize preclinical and clinical findings. We em...
Source: Drug Discovery Today - January 25, 2024 Category: Drugs & Pharmacology Authors: Cheng-Zhe Jian Li Lin Chia-Lang Hsu Yu-Hsin Chen Chiun Hsu Ching-Ting Tan Da-Liang Ou Source Type: research
Nanoformulations of chemotherapeutic activators of the cGAS-STING pathway in tumor chemoimmunotherapy
Drug Discov Today. 2024 Jan 24;29(3):103892. doi: 10.1016/j.drudis.2024.103892. Online ahead of print.ABSTRACTChemotherapeutic drugs to activate the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway have been exploited for tumor chemoimmunotherapy. The clinical translation of chemotherapeutic cGAS-STING activators is hindered by the lack of safe, efficient, and specific delivery strategies. Nanodrug delivery systems (NDDS) designed for reducing toxic effects and improving transport effectiveness potentiate in vivo delivery of chemotherapeutic cGAS-STING ac...
Source: Drug Discovery Today - January 25, 2024 Category: Drugs & Pharmacology Authors: Lingzhi Wang Zhuo Yu Jihong Zhang Jianfeng Guo Source Type: research
Informatic challenges and advances in illuminating the druggable proteome
Drug Discov Today. 2024 Jan 22;29(3):103894. doi: 10.1016/j.drudis.2024.103894. Online ahead of print.ABSTRACTThe 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 challenges and advances in annotating understudied members of the druggable proteome. We demonstrate the applicati...
Source: Drug Discovery Today - January 24, 2024 Category: Drugs & Pharmacology Authors: Rahil Taujale Nathan Gravel Zhongliang Zhou Wayland Yeung Krystof Kochut Natarajan Kannan Source Type: research
Drugging the entire human proteome: Are we there yet?
Drug Discov Today. 2024 Jan 19;29(3):103891. doi: 10.1016/j.drudis.2024.103891. Online ahead of print.ABSTRACTEach 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 of compounds to thousands of targets. Although preliminary proteome-wide screens are now within our grasp, f...
Source: Drug Discovery Today - January 21, 2024 Category: Drugs & Pharmacology Authors: Micholas Dean Smith L Darryl Quarles Omar Demerdash Jeremy C Smith Source Type: research
Summary and future of medicine for hereditary angioedema
Drug Discov Today. 2024 Jan 19;29(3):103890. doi: 10.1016/j.drudis.2024.103890. Online ahead of print.ABSTRACTHereditary 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 effects and mechanisms of HAE drugs, and it also discusses possible development directions and targets to enhan...
Source: Drug Discovery Today - January 21, 2024 Category: Drugs & Pharmacology Authors: Lei Ding Meng-Jiao Zhang Guo-Wu Rao Source Type: research
Spatial transcriptomics data and analytical methods: An updated perspective
Drug Discov Today. 2024 Jan 18;29(3):103889. doi: 10.1016/j.drudis.2024.103889. Online ahead of print.ABSTRACTSpatial 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 ST data. These platforms, integrating AI techniques, offer a promising avenue for understanding disease mechanisms and ...
Source: Drug Discovery Today - January 20, 2024 Category: Drugs & Pharmacology Authors: None Danishuddin Shawez Khan Jong Joo Kim Source Type: research
The European Lead Factory: Results from a decade of collaborative, public-private, drug discovery programs
Drug Discov Today. 2024 Jan 18;29(3):103886. doi: 10.1016/j.drudis.2024.103886. Online ahead of print.ABSTRACTThe 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 and expanded through library synthesis by chemistry-specialized SMEs. The library has been screened against ∼2...
Source: Drug Discovery Today - January 20, 2024 Category: Drugs & Pharmacology Authors: 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 Source Type: research
