Review
Pharmacology & Pharmacy
Sachin Nashik Sanap, Amol Chhatrapati Bisen, Ashwini Kedar, Sristi Agrawal, Rabi Sankar Bhatta
Summary: Despite advancements in CNS research, CNS illnesses remain the most important cause of mental disability worldwide, highlighting the need for effective medications and pharmacotherapy. The kinetics and effects of CNS drugs are influenced by various mechanisms, including the blood-brain barrier and condition-dependent processes. Understanding inter-species and inter-condition variances is crucial for improving CNS therapeutics and drug development.
CURRENT PHARMACEUTICAL DESIGN
(2023)
Article
Chemistry, Medicinal
Richard C. Hewer, Louisa A. Christie, Kevin J. Doyle, Xiao Xu, Maxine J. Roberts, Louise Dickson, Toni Cheung, David H. Cadwalladr, Philip Pickford, Martin Teall, Justin A. C. Powell, Steven Sheardown, Lakshminarayana Narayana, Nicola L. Brice, Lee A. Dawson, Mark Carlton, Roland W. Burli
Summary: Based on our transcriptomics data, we identified GPR55 as a potential target for treating motor symptoms in Parkinson's disease. Through screening, we found compounds with high potency as agonists for both human and rat GPR55. These compounds demonstrated biased signaling and were selective over other cannabinoid receptors. This study provides insights into the role of GPR55 in the brain.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yuanguang Chen, Lu Chen, Huashen Xu, Ruolin Cao, Christophe Morisseau, Maoying Zhang, Yajie Shi, Bruce D. Hammock, Jieru Wang, Junning Zhuang, Zhongbo Liu, Guoliang Chen
Summary: Soluble epoxide hydrolase (sEH) has emerged as a promising target for developing anti-inflammatory drugs. Compound G1, with hydrophilic group homopiperazine and hydrophobic fragment propionyl, was found to inhibit sEH at picomolar levels. G1 demonstrated good stability, moderate plasma protein binding, and high oral bioavailability in rats. It showed significant analgesic effects in mice, and improved pancreatic injury and survival in sepsis models. Western blot and ELISA assays showed decreased expression of inflammatory markers. G1 is a potential drug candidate for treating inflammation-induced diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Hristo L. Svilenov, Paolo Arosio, Tim Menzen, Peter Tessier, Pietro Sormanni
Summary: Antibody drugs need to have high-binding affinity for target antigens and favorable drug-like properties. Traditional approaches in antibody drug development require extensive experimentation to produce and optimize candidates. Integrating new methods can optimize the process of selecting antibodies with desired properties. This article summarizes techniques that can complement conventional tools, reduce physicochemical liabilities in initial discovery, and optimize antibody features during early-stage engineering. Biophysical and computational approaches are also highlighted to predict degradation pathways and reduce extensive experimentation.
Article
Virology
Dongwei Kang, Jinxuan Yang, Lingjin Kong, Ronghua Luo, Xusheng Huang, Tao Zhang, Mengdi Ma, Da Feng, Zhao Wang, Hao Fang, Peng Zhan, Yongtang Zheng, Xinyong Liu
Summary: K-5a2 is a potential anti-HIV drug with high anti-HIV-1 activity, synergistic effects with other antiviral drugs, and favorable pharmacokinetics and safety profiles.
Article
Pharmacology & Pharmacy
Manoj Samant, John Ziemniak, John F. Paolini
Summary: This study investigated the safety, pharmacokinetics, receptor occupancy, and pharmacodynamics of the anti-CD40 monoclonal antibody KPL-404. The results showed that KPL-404 exhibited dose-dependent changes in pharmacokinetic parameters and long duration of receptor occupancy, leading to suppression of immune response. These findings support further investigation of KPL-404 in various indications.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Cardiac & Cardiovascular Systems
Joanna Osmanska, Katriona Brooksbank, Kieran F. Docherty, Stacy Robertson, Kirsty Wetherall, Alex McConnachie, Jerry Hu, Roy S. Gardner, Andrew L. Clark, Iain B. Squire, Paul R. Kalra, Pardeep S. Jhund, Pieter Muntendam, John J. McMurray, Mark C. Petrie, Ross T. Campbell
Summary: This study compared the bioavailability, pharmacokinetic and pharmacodynamic profiles between subcutaneous and intravenous furosemide, and described the use of a mini-pump for subcutaneous administration. The results showed that subcutaneous furosemide had similar bioavailability to intravenous furosemide, and administration via a patch pump was feasible and well tolerated.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Krishna Kanta Ghosh, Parasuraman Padmanabhan, Chang-Tong Yang, David Chee Eng Ng, Mathangi Palanivel, Sachin Mishra, Christer Halldin, Balazs Gulyas
Summary: Positron emission tomography (PET) is a widely used nuclear functional imaging technique, particularly in central nervous system (CNS) and oncological disorders. It can accelerate drug discovery and development by monitoring drug distribution and effects, providing important references for clinical application.
DRUG DISCOVERY TODAY
(2022)
Article
Pharmacology & Pharmacy
Mahendra Kumar Prajapati, Rohan Pai, Pradeep Vavia
Summary: The study aimed to develop a liposomal system with folate modification to enhance the selectivity of anticancer drugs towards ovarian tumor cells and reduce toxicity to healthy cells. Results showed that the optimized liposome significantly reduced tumor volume and weight, and improved survival rate.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Manoj Samant, John Ziemniak, John F. Paolini
Summary: This study evaluated the safety, pharmacokinetics, receptor occupancy, and pharmacodynamics of the anti-CD40 monoclonal antibody KPL-404. The results showed that KPL-404 had a prolonged duration of receptor occupancy and suppressed the immune response. These findings support further investigation of KPL-404 in different indications.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Review
Chemistry, Analytical
Lin-Sen Qing, Tian-Tian Wang, Han-Yue Luo, Jia-Lan Du, Run-Yue Wang, Pei Luo
Summary: Natural products are still the main source of drug candidates in new drug discovery. Microfluidic technology offers a rapid and efficient research system for natural products through miniaturizing the analytical process onto a single chip. This review comprehensively summarizes the design and applications of microfluidic devices in analyzing, evaluating, and studying natural products, as well as discussing limitations and future research directions.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Vanessa Martins, Lynsey Fazal, Aram Oganesian, Alpesh Shah, Jessie Stow, Hugh Walton, Nicola Wilsher
Summary: Paxlovid, a drug combining nirmatrelvir and ritonavir, has been approved for emergency use by the FDA for treating COVID-19. Co-administration with pharmacoenhancers can enhance the pharmacokinetics and provide various benefits such as ensuring therapeutic exposure and reducing toxic metabolite formation. Technology advancements and improved integration between interdisciplinary teams can enhance drug discovery outcomes.
Article
Pharmacology & Pharmacy
Thuan Thi Duong, Tran Thi Hai Yen, Linh Tran Nguyen, Thuy-Duong Nguyen, Thi-Quynh-Trang Nguyen, Thi-Ha-Lien Nghiem, Huyen Thanh Pham, Ain Raal, Jyrki Heinamaki, Thi-Minh-Hue Pham
Summary: The study successfully designed proliposomes loaded with Berberine, which greatly enhanced the oral bioavailability and therapeutic effects, demonstrating significant cholesterol-lowering effects in animal experiments.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Ting-jian Zhang, Yi Zhang, Zhen-hao Zhang, Zhao-ran Wang, Xu Zhang, Sen-sen Hu, Peng-fei Lu, Shuai Guo, Fan-hao Meng
Summary: In this study, a series of new compounds were designed, synthesized, and evaluated for their inhibitory activities against xanthine oxidase. Compound 9m showed the most potent inhibition, with a low IC50 value and favorable drug-like properties.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Medicine, Research & Experimental
Emily K. Makowski, Lina Wu, Priyanka Gupta, Peter M. Tessier
Summary: Developing monoclonal antibodies as therapeutic agents for diverse human disorders has sparked intense interest. Key recent advances in high-throughput methods for identifying antibodies with desirable properties have shown great promise in rational antibody design and prediction of drug-like behaviors, but outstanding challenges remain in fully realizing their potential to minimize development times and improve success rates in the clinic.
