Review
Pharmacology & Pharmacy
Jingbo Yang, Yiyang Cai, Kairui Zhao, Hongbo Xie, Xiujie Chen
Summary: This review provides a summary and classification of molecular fingerprints, emphasizing their significance in early drug research and development. It serves as a guide for selecting appropriate fingerprints for compounds in drug R&D.
DRUG DISCOVERY TODAY
(2022)
Article
Pharmacology & Pharmacy
Ellie Esfandiari Nazzaro, Fahad Y. Sabei, Walter K. Vogel, Mohamad Nazari, Katelyn S. Nicholson, Philip R. Gafken, Olena Taratula, Oleh Taratula, Monika A. Davare, Mark Leid
Summary: Ewing's sarcoma is a rare and aggressive cancer of bone and soft tissue characterized by specific chromosomal translocations. Current cytotoxic chemotherapies effectively treat localized disease but can lead to treatment-related morbidities, and the survival rate for patients with relapsed or metastatic disease remains low. A new compound, ML111, was identified through high-throughput screening and showed promising inhibitory effects on Ewing's sarcoma cells in vitro and in vivo, suggesting its potential as a new drug lead for further preclinical studies.
Review
Chemistry, Medicinal
Igor Jose dos Santos Nascimento, Paulo Fernando da Silva Santos-Junior, Joao Xavier de Araujo-Junior, Edeildo Ferreira da Silva-Junior
Summary: The Ebola Virus (EBOV) is an infectious disease that primarily affects the cardiovascular system and is transmitted through contact with secretions from infected wild animals. Recent outbreaks have drawn attention to the need for effective treatments, with the most advanced drug being remdesivir, although more research and investments are required for the development of new antiviral drugs to combat these pathogens.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Andrej Emanuel Cotman, Martina Durcik, Davide Benedetto Tiz, Federica Fulgheri, Daniela Secci, Masa Sterle, Stefan Mozina, Ziga Skok, Nace Zidar, Anamarija Zega, Janez Ilas, Lucija Peterlin Masic, Tihomir Tomasic, Diarmaid Hughes, Douglas L. Huseby, Sha Cao, Linnea Garoff, Talia Berruga Fernandez, Paraskevi Giachou, Lisa Crone, Ivailo Simoff, Richard Svensson, Bryndis Birnir, Sergiy V. Korol, Zhe Jin, Francisca Vicente, Maria C. Ramos, Mercedes de la Cruz, Bjorn Glinghammar, Lena Lenhammar, Sara R. Henderson, Julia E. A. Mundy, Anthony Maxwell, Clare E. M. Stevenson, David M. Lawson, Guido V. Janssen, Geert Jan Sterk, Danijel Kikelj
Summary: We have developed compounds that show promising activity against antibiotic-resistant bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa, which are on the WHO priority list. Compound 27, derived from DNA gyrase inhibitor 1, exhibited improved solubility, inhibition of topoisomerase IV, and no cross-resistance to novobiocin. Further optimization steps led to analogs of 27 with improved plasma distribution and retained anti-Gram-negative activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Jiang Hong Cai, Xuan Zhe Zhu, Peng Yue Guo, Peter Rose, Xiao Tong Liu, Xia Liu, Yi Zhun Zhu
Summary: Drug discovery is a challenging process with a high failure rate. Click chemistry and computer-aided drug design (CADD) have emerged as promising approaches for new drug development. This review summarizes the recent advancements in click and computational chemistry, including efficient synthesis of drug candidates, modification of natural products, targeted delivery systems, and computer-aided drug discovery for target identification and compound optimization. These advancements provide inspiration for novel drug development in the future.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Koon Mook Kang, Yejin Jang, Sang Soo Lee, Mi Sun Jin, Chang-Duk Jun, Meehyein Kim, Yong-Chul Kim
Summary: This study reports the development of novel SARS-CoV-2 Mpro inhibitors derived from carmofur and their optimization through experimental and simulation methods. Two compounds with strong inhibitory activity were identified, and their antiviral effects against SARS-CoV-2 were confirmed, suggesting their potential as lead compounds for the development of anti-SARS-CoV-2 agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Tianduanyi Wang, Otto I. Pulkkinen, Tero Aittokallio
Summary: Most drug molecules have the ability to modulate multiple target proteins, which can lead to both therapeutic effects and unwanted side effects. Evaluating the selectivity of a compound is an important factor in drug development and repurposing efforts. Traditional methods for characterizing selectivity fall short in quantifying how selective a compound is against a particular target protein. In this study, we propose an optimization-based selectivity scoring method that allows for the identification of potent and selective compounds against given kinase targets. We demonstrate the effectiveness of this method in finding highly selective compounds in computational experiments using a large-scale kinase inhibitor dataset.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Ziwen Zhang, Shi-Long Zhang, Chengyao Wu, Huan-Huan Li, Liang Zha, Jingbo Shi, Xinhua Liu, Hua-Li Qin, Wenjian Tang
Summary: SuFEx click chemistry has been demonstrated as a powerful method for the rapid synthesis of sulfonamide inhibitors for high-throughput testing of cholinesterase activity. By applying this methodology, a diverse library of sulfonamides was synthesized and directly screened to yield drug-like inhibitors with significantly enhanced potency. The improved molecule J8-A34 showed effectiveness in improving cognitive function in a mouse model. This study highlights the potential of SuFEx click chemistry for accelerating the development of biological probes and drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Daiki Erikawa, Nobuaki Yasuo, Masakazu Sekijima
Summary: In this study, a SMILES-based generative model was developed to generate molecules starting from a certain molecule, using Monte Carlo Tree Search and a Recurrent Neural Network. The method was validated using a molecule dataset obtained from the ZINC database, successfully generating molecules optimized for drug-likeness (QED) and penalized octanol-water partition coefficient (PLogP) objectives.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Obstetrics & Gynecology
Minuo Yin, Jiaming Zhang, Xinliu Zeng, Hanke Zhang, Ying Gao
Summary: This study identified significant gene modules related to OE, involving the PI3K/Akt and aging pathways. ITPR1 expression was found to be elevated in OE lesions and its knockdown inhibited cell proliferation and induced apoptosis in HESCs. Candidate drugs camptothecin and irinotecan were identified as promising for OE treatment, with camptothecin suppressing HESC proliferation and inducing apoptosis. The study also validated the therapeutic effect of camptothecin in an OE mouse model.
FERTILITY AND STERILITY
(2021)
Article
Biochemical Research Methods
Nansu Zong, Ning Li, Andrew Wen, Victoria Ngo, Yue Yu, Ming Huang, Shaika Chowdhury, Chao Jiang, Sunyang Fu, Richard Weinshilboum, Guoqian Jiang, Lawrence Hunter, Hongfang Liu
Summary: In this study, a benchmark called BETA is introduced to comprehensively evaluate the performance and limitations of drug-target predictive models. It provides a network with a large number of biomedical concepts and associations, as well as various evaluation strategies, for the selection of computational strategies in drug repurposing and target discovery.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Biochemistry & Molecular Biology
Darren R. Flower
Summary: The underperformance of the pharmaceutical discovery process is mainly due to profit-driven rather than society-driven search for new pharmaceutical products. Insufficient funding and lack of systematic approaches result in underuse of innovative methods and limitations of dominant methodologies. To fully capitalize on the potential of pharmaceutical intervention, a fundamental shift in attitude towards reliance on computational approaches and moving away from commercial imperatives is essential.
Article
Chemistry, Medicinal
Gilda Padalino, Nelly El-Sakkary, Lawrence J. Liu, Chenxi Liu, Danielle S. G. Harte, Rachel E. Barnes, Edward Sayers, Josephine Forde-Thomas, Helen Whiteland, Marcella Bassetto, Salvatore Ferla, George Johnson, Arwyn T. Jones, Conor R. Caffrey, Iain Chalmers, Andrea Brancale, Karl F. Hoffmann
Summary: Recent research has identified a promising anti-schistosomal scaffold in the quinoxaline core, which has shown improved activity and selectivity through chemical optimization. This could potentially serve as an urgently needed alternative to praziquantel for assisting in schistosomiasis elimination strategies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Multidisciplinary Sciences
Kim E. Jelfs
Summary: This article introduces the application of computational modeling in the discovery of supramolecular materials, which plays an important role in structure, property, and synthesis prediction. Artificial intelligence techniques have the potential to impact the field, but close integration with experimental materials discovery programs is also crucial.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Peng Li, Chujie Bai, Lingmin Zhan, Haoran Zhang, Yuanyuan Zhang, Wuxia Zhang, Yingdong Wang, Jinzhong Zhao
Summary: Identifying the biological targets of a compound is crucial for understanding drug mechanisms and developing new drugs. The Connectivity Map concept connects genes, drugs, and diseases based on gene-expression signatures. However, existing methods are inefficient due to the need for reference drugs. In this study, we developed a procedure to extract target-induced gene modules and identified target gene clusters. Additionally, we proposed a gene module pair-based approach to predict novel compound-target interactions, leading to the discovery of new inhibitors for PI3K pathway proteins.
FRONTIERS IN PHARMACOLOGY
(2023)