Revolutionizing viral disease treatment: Phase separation and lysosome/exosome targeting as new areas and new paradigms for antiviral drug research
Drug Discov Today. 2024 Jan 18;29(3):103888. doi: 10.1016/j.drudis.2024.103888. Online ahead of print.ABSTRACTWith 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 drug discovery methods primarily rely on random screening and structure-based optimization, and new approaches are req...
Source: Drug Discovery Today - January 20, 2024 Category: Drugs & Pharmacology Authors: Shaoqing Du Xueping Hu Xinyong Liu Peng Zhan Source Type: research
Communicating computational workflows in a regulatory environment
Drug Discov Today. 2024 Jan 12:103884. doi: 10.1016/j.drudis.2024.103884. Online ahead of print.ABSTRACTThe 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 to institutions and companies communicating computations in a regulatory environment. BioCompute Objects (BCOs; an instanc...
Source: Drug Discovery Today - January 14, 2024 Category: Drugs & Pharmacology Authors: Jonathon G Keeney Naila Gulzar Jack B Baker Ondrej Klempir Geoffrey D Hannigan Danny A Bitton Julia M Maritz Charles H S King Janisha A Patel Paul Duncan Raja Mazumder Source Type: research
Drug-drug co-amorphous systems: An emerging formulation strategy for poorly water-soluble drugs
Drug Discov Today. 2024 Feb;29(2):103883. doi: 10.1016/j.drudis.2024.103883. Epub 2024 Jan 14.ABSTRACTOvercoming 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 as a novel strategy to not only enable enhanced dissolution and physical stability of the individual drugs within the system ...
Source: Drug Discovery Today - January 14, 2024 Category: Drugs & Pharmacology Authors: Hongge Wang Peixu Zhao Ruilong Ma Jirun Jia Qiang Fu Source Type: research
Illuminating function of the understudied druggable kinome
Drug Discov Today. 2024 Jan 11;29(3):103881. doi: 10.1016/j.drudis.2024.103881. Online ahead of print.ABSTRACTThe 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, use of understudied kinases tagged with a miniTurbo-biotin ligase to determine interaction networks by proximity-dep...
Source: Drug Discovery Today - January 13, 2024 Category: Drugs & Pharmacology Authors: Shawn M Gomez Alison D Axtman Timothy M Willson Michael B Major Reid R Townsend Peter K Sorger Gary L Johnson Source Type: research
Overview of the Knowledge Management Center for Illuminating the Druggable Genome
Drug Discov Today. 2024 Jan 11;29(3):103882. doi: 10.1016/j.drudis.2024.103882. Online ahead of print.ABSTRACTThe 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 web-based informatics platform (Pharos). These data include experimental, computational, and text-mined information on ...
Source: Drug Discovery Today - January 13, 2024 Category: Drugs & Pharmacology Authors: 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 Math é Sorin Avram Jeremy S Edwards Source Type: research
Design strategies and recent development of bioactive modulators for glutamine transporters
Drug Discov Today. 2024 Feb;29(2):103880. doi: 10.1016/j.drudis.2024.103880. Epub 2024 Jan 11.ABSTRACTGlutamine 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 transporters, marked by breakthroughs in understanding of their protein structures and the discovery of novel inhibitor...
Source: Drug Discovery Today - January 12, 2024 Category: Drugs & Pharmacology Authors: Xinying Cheng Yezhi Wang Guangyue Gong Pei Shen Zhiyu Li Jinlei Bian Source Type: research
Data standards in drug discovery: A long way to go
Drug Discov Today. 2024 Feb;29(2):103879. doi: 10.1016/j.drudis.2024.103879. Epub 2024 Jan 11.ABSTRACTEach 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 and significantly more expensive, it is crucial to maximize the value of these valuable data through improved standard...
Source: Drug Discovery Today - January 12, 2024 Category: Drugs & Pharmacology Authors: Jens M Kelm Marc Ferrer Martin-Immanuel Bittner Madhu Lal-Nag Source Type: research
Recent discoveries of the role of histone modifications and related inhibitors in pathological cardiac hypertrophy
Drug Discov Today. 2024 Feb;29(2):103878. doi: 10.1016/j.drudis.2024.103878. Epub 2024 Jan 10.ABSTRACTPathological 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 for pathological cardiac hypertrophy. In this review, we provide a comprehensive summary of the roles of histone modifica...
Source: Drug Discovery Today - January 11, 2024 Category: Drugs & Pharmacology Authors: Ke-Jia Wu Qi Chen Chung-Hang Leung Ning Sun Fei Gao Zhaoyang Chen Source Type: research
Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer
Drug Discov Today. 2024 Feb;29(2):103875. doi: 10.1016/j.drudis.2023.103875. Epub 2024 Jan 3.ABSTRACTN6-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 been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progres...
Source: Drug Discovery Today - January 4, 2024 Category: Drugs & Pharmacology Authors: None Mao-Mao Jin-Jing Zhang Yue-Ping Xu Min-Min Shao Meng-Chuan Wang Source Type: research
Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer
Drug Discov Today. 2024 Jan 3:103875. doi: 10.1016/j.drudis.2023.103875. Online ahead of print.ABSTRACTN6-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 been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progr...
Source: Drug Discovery Today - January 4, 2024 Category: Drugs & Pharmacology Authors: None Mao-Mao Jin-Jing Zhang Yue-Ping Xu Min-Min Shao Meng-Chuan Wang Source Type: research
Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer
Drug Discov Today. 2024 Jan 3;29(2):103875. doi: 10.1016/j.drudis.2023.103875. Online ahead of print.ABSTRACTN6-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 been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer...
Source: Drug Discovery Today - January 4, 2024 Category: Drugs & Pharmacology Authors: None Mao-Mao Jin-Jing Zhang Yue-Ping Xu Min-Min Shao Meng-Chuan Wang Source Type: research
Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer
Drug Discov Today. 2024 Jan 2:103875. doi: 10.1016/j.drudis.2023.103875. Online ahead of print.ABSTRACTN6-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 been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progr...
Source: Drug Discovery Today - January 4, 2024 Category: Drugs & Pharmacology Authors: None Mao-Mao Jin-Jing Zhang Yue-Ping Xu Min-Min Shao Meng-Chuan Wang Source Type: research
Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer
Drug Discov Today. 2024 Jan 2:103875. doi: 10.1016/j.drudis.2023.103875. Online ahead of print.ABSTRACTN6-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 been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progr...
Source: Drug Discovery Today - January 4, 2024 Category: Drugs & Pharmacology Authors: None Mao-Mao Jin-Jing Zhang Yue-Ping Xu Min-Min Shao Meng-Chuan Wang Source Type: research
Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Drug Discov Today. 2023 Dec 26:103865. doi: 10.1016/j.drudis.2023.103865. Online ahead of print.ABSTRACTPROteolysis 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 the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportuni...
Source: Drug Discovery Today - December 28, 2023 Category: Drugs & Pharmacology Authors: Wenzhan Yang Sugandha Saboo Liping Zhou Sean Askin Annette Bak Source Type: research
Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Drug Discov Today. 2023 Dec 26:103865. doi: 10.1016/j.drudis.2023.103865. Online ahead of print.ABSTRACTPROteolysis 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 the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportuni...
Source: Drug Discovery Today - December 28, 2023 Category: Drugs & Pharmacology Authors: Wenzhan Yang Sugandha Saboo Liping Zhou Sean Askin Annette Bak Source Type: research
