Review
Pharmacology & Pharmacy
Jeffrey J. Widrick, Matthias R. Lambert, Louis M. Kunkel, Alan H. Beggs
Summary: This review article summarizes the application of zebrafish larvae in large-scale drug discovery, focusing on the experimental methods and interpretation of swimming behavior. Attention to animal husbandry, experimental design, data acquisition, and interpretation of results can improve the accuracy and stability of screening outcomes.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Cell Biology
Viviana L. Vedder, Tobias Reinberger, Syed M. I. Haider, Luis Eichelmann, Nadine Odenthal, Salim Abdelilah-Seyfried, Zouhair Aherrahrou, Maximilian Breuer, Jeanette Erdmann
Summary: Cardiovascular diseases (CVDs) are the leading cause of death, with congenital heart diseases being the most common congenital defects. However, the developmental toxicity of many FDA-approved drugs is rarely investigated. To improve our understanding of drug side effects, a high-content drug screen was performed using zebrafish as a model for cardiovascular analyses. A Python-based tool called pyHeart4Fish was developed for automated quantification of cardiac parameters. The study found significant effects of certain drugs on heart rate and identified multiple contractility defects and arrhythmias.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Editorial Material
Pharmacology & Pharmacy
Alessandro Datti
Summary: High-throughput screening (HTS) is a powerful technology in drug discovery, but drug repositioning primarily relies on serendipitous observations rather than experimental routes. The disconnect between technological progress in academia and the challenges of drug repositioning can be addressed through a visionary approach called labsourcing, which involves aggregating expertise to perform multiple bioassays using a common screening collection. This approach has advantages such as addressing discrepancies, generating large amounts of data, providing educational benefits, and democratizing research.
DRUG DISCOVERY TODAY
(2023)
Review
Computer Science, Artificial Intelligence
Heba Askr, Enas Elgeldawi, Heba Aboul Ella, Yaseen A. M. M. Elshaier, Mamdouh M. Gomaa, Aboul Ella Hassanien
Summary: Recently, there has been a lot of attention on using artificial intelligence (AI) in drug discovery due to its ability to significantly reduce the time and cost of developing new drugs. This paper presents a systematic literature review (SLR) that integrates recent advancements in deep learning (DL) technology and its applications in various stages of drug development. The review covers topics such as drug-target interactions (DTIs), drug-drug similarity interactions (DDIs), drug sensitivity and responsiveness, and drug-side effect predictions. The paper also provides an overview of explainable AI (XAI) in supporting drug discovery problems, discusses drug dosing optimization and success stories, and proposes digital twining (DT) and open issues as future research challenges. Challenges to be addressed and future research directions are identified, and an extensive bibliography is included.
ARTIFICIAL INTELLIGENCE REVIEW
(2023)
Review
Pharmacology & Pharmacy
Esra Balikci, Anne-Sophie M. C. Marques, Jesper S. Hansen, Kilian V. M. Huber
Summary: The rational development of new therapeutics requires a thorough understanding of how aberrant signaling affects cellular homeostasis and causes human disease. Chemical probes are powerful tools for drug discovery that have led to fundamental insights into biological processes and have paved the way for the development of first-in-class drugs.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Review
Pharmacology & Pharmacy
Xiaobo Wang, Jin-Bao Zhang, Kai-Jie He, Fen Wang, Chun-Feng Liu
Summary: Neurodegenerative diseases (NDD), such as Alzheimer's disease and Parkinson's disease, are characterized by neuron loss leading to motor and cognitive decline. Effective treatments for NDD are lacking, but zebrafish models show promise for drug discovery with their high homology to humans. High-throughput platforms in zebrafish research are expected to advance future NDD studies.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Yantao Ma, Handan Xie, Xiaomin Du, Lipeng Wang, Xueqin Jin, Qianqian Zhang, Yawen Han, Shicheng Sun, Longteng Wang, Xiang Li, Changjiang Zhang, Mengdi Wang, Cheng Li, Jun Xu, Zhuo Huang, Xiaoqun Wang, Zhen Chai, Hongkui Deng
Summary: This study demonstrates that small molecules can reprogram astrocytes into neurons in the adult mouse brain. The in situ chemically induced neurons show similarities to endogenous neurons in terms of marker expression, electrophysiological properties, and synaptic connectivity, providing a potential approach for developing neuronal replacement therapies.
Review
Chemistry, Medicinal
Yiwen Hong, Yan Luo
Summary: Zebrafish serves as an ideal model for eye disorders research, with its genetic and embryonic accessibility making it a popular tool for elucidating disease mechanisms and exploring novel drug treatments.
Editorial Material
Immunology
Fei Yi, Christopher A. Klebanoff
Summary: CRISPR-Cas9 is a powerful tool for genetic screens, but vector immunogenicity may introduce artifacts. A new strategy to erase vector-associated neoantigens has been reported in a recent study, allowing a more physiologic assessment of tumor-immune cell interactions in immunocompetent hosts.
Article
Biochemistry & Molecular Biology
Ankita Kumari, Xin-An Zeng, Abdul Rahaman, Muhammad Adil Farooq, Yanyan Huang, Mahafooj Alee, Runyu Yao, Murtaza Ali, Ibrahim Khalifa, Omnia Badr
Summary: This study developed a simple and efficient in vivo assay using transgenic zebrafish larvae to identify compounds that can modulate M-cell regeneration. Through screening and in silico analysis, FDA-approved drugs with the potential to inhibit axon regeneration were identified, and PTEN and SOCS3 were identified as potential signaling molecules responsible for reducing axon regeneration. Additionally, the study demonstrated the toxic effects of these compounds.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Chemistry, Medicinal
Shenxin Zeng, Wenhai Huang, Xiaoliang Zheng, Liyan Cheng, Zhimin Zhang, Jian Wang, Zhengrong Shen
Summary: PROTAC is a novel drug discovery paradigm that targets proteins for degradation. ARV-110, an orally small molecule PROTAC designed for Androgen receptor, has entered clinical trials, marking a new avenue for PROTAC development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Summaya Perveen, Diksha Kumari, Kuljit Singh, Rashmi Sharma
Summary: The emergence of drug-resistant strains of tuberculosis poses a global health concern. Treatment of multidrug-resistant/extensively drug-resistant TB is complicated and requires second-line drugs with greater side effects. Recent approvals of new drugs for MDR/XDR-TB have provided impetus for TB drug discovery, highlighting the importance of combating TB through multidisciplinary approaches and leveraging recent advances in understanding the disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Santanu Datta
Summary: Despite a great need for new antibiotics, the postgenomic era of drug discovery has seen only a few molecules registered for clinical use, primarily due to scientific failures. Small biotech companies are now mitigating these risks and moving forward using new strategies to identify new antibiotics.
DRUG DISCOVERY TODAY
(2021)
Article
Chemistry, Multidisciplinary
Chong Lu, Shien Liu, Weihua Shi, Jun Yu, Zhou Zhou, Xiaoxiao Zhang, Xiaoli Lu, Faji Cai, Ning Xia, Yikai Wang
Summary: SECSE is a novel gene design platform that integrates artificial intelligence and deep learning to efficiently search and generate small molecules with potential drug activity.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Medicine, Research & Experimental
Loretta M. S. Lau, Chelsea Mayoh, Jinhan Xie, Paulette Barahona, Karen L. MacKenzie, Marie Wong, Alvin Kamili, Maria Tsoli, Tim W. Failes, Amit Kumar, Emily V. A. Mould, Andrew Gifford, Shu-Oi Chow, Mark Pinese, Jamie Fletcher, Greg M. Arndt, Dong-Anh Khuong-Quang, Carol Wadham, Georgina Eden, Peter Trebilcock, Swapna Joshi, Stephanie Alfred, Anjana Gopalakrishnan, Aaminah Khan, Dylan Grebert Wade, Patrick A. Strong, Elodie Manouvrier, Lisa T. Morgan, Roxanne Cadiz, Caitlin Ung, David M. Thomas, Katherine M. Tucker, Meera Warby, Geoffrey B. McCowage, Luciano Dalla-Pozza, Jennifer A. Byrne, Federica Saletta, Andrew Fellowes, Stephen B. Fox, Murray D. Norris, Vanessa Tyrrell, Toby N. Trahair, Richard B. Lock, Mark J. Cowley, Paul G. Ekert, Michelle Haber, David S. Ziegler, Glenn M. Marshall
Summary: The study developed a precision medicine platform involving rapid high-throughput drug screening and patient-derived xenografting for high-risk pediatric cancer patients. Results showed that 70% of patients across the entire testing platform were able to find treatment options, with some patients experiencing clinical benefits after changes in treatment plans.
EMBO MOLECULAR MEDICINE
(2022)