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Prostate cancer (PCa) is one of the leading cancers in men and the lack of suitable biomarkers or their modulators results in poor prognosis. Membrane proteins (MPs) have a crucial role in the development and progression of PCa and can be attractive therapeutic targets. However, experimental limitations in targeting MPs hinder effective biomarker and inhibitor discovery. To overcome this barrier, computational methods can yield structural insights and screen large libraries of compounds, accelerating lead identification and optimization. In this review, we examine current breakthroughs in computer-aided drug design (CADD), with emphasis on structure-based approaches targeting the most relevant membrane-bound PCa biomarkers.
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http://dx.doi.org/10.1016/j.drudis.2024.104130 | DOI Listing |
FEBS J
September 2025
Neutron Scattering Division, Oak Ridge National Laboratory, USA.
Serine hydroxymethyltransferase (SHMT) is a critical enzyme in the one-carbon (1C) metabolism pathway catalyzing the reversible conversion of L-Ser into Gly and concurrent transfer of 1C unit to tetrahydrofolate (THF) to give 5,10-methylene-THF (5,10-MTHF), which is used in the downstream syntheses of biomolecules critical for cell proliferation. The cellular 1C metabolism is hijacked by many cancer types to support cancer cell proliferation, making SHMT a promising target for the design and development of novel small-molecule antimetabolite chemotherapies. To advance structure-assisted drug design, knowledge of SHMT catalysis is crucial, but can only be fully realized when the atomic details of each reaction step governed by the acid-base catalysis are elucidated by visualizing active site hydrogen atoms.
View Article and Find Full Text PDFInjury
August 2025
Institute for Research in Military Medicine (IRMM), Faculty of Medicine, The Hebrew University of Jerusalem and the Israel Defense Forces Medical Corps, Jerusalem, Israel; Department of Military Medicine ("Tzameret"), Faculty of Medicine, The Hebrew University of Jerusalem, and the Israel Defense Fo
Background: Hemorrhage remains the principal cause of death on the battlefield. It is suggested that Tranexamic acid (TXA) can improve survival of severely-bleeding casualties. The intravenous approach is not always available in the pre-hospital setting.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Newcastle University, School of Natural and Environmental Sciences, Newcastle upon Tyne, UK NE1 7RU. Electronic address:
RNA interference (RNAi) is an endogenous eukaryote viral defence mechanism representing a unique form of post-transcriptional gene silencing that can be induced via the exongenous application of dsRNA. Due to its high specificity, dsRNA-based biopesticides are being developed to control pest insects. Whilst many lepidopteran species are recalcitrant to RNAi, Tuta absoluta, a polyphagous insect responsible for extensive crop damage, is sensitive.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China. Electronic address:
Potato virus Y (PVY) is one of the most economically detrimental phytoviruses affecting global Solanaceae, possessing challenges in agrochemical control. The structural elucidation of PVY coat protein (CP) offers opportunities for the rational design of CP-targeted antivirals; however, the feasibility of identifying lead compounds via virtual screening remains largely unexplored. Herein, we report the successful case of structure-based virtual screening leveraging PVY CP, enabling the identification of a structurally novel lead with a unique mechanism of action.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Department of Entomology and Nematology, Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address:
The global rise of mosquito-borne diseases and widespread resistance to existing insecticides highlight the urgent need for novel, field-relevant mosquitocides. Here, we report the development and validation of a high-throughput, in vivo screening assay capable of evaluating adult mosquito toxicity across large chemical libraries. Utilizing a 96-well plate format, this assay enables simultaneous testing of hundreds of compounds per run using both net and filter paper substrates, with direct measurement of adult mosquito knockdown and mortality via tarsal contact - an exposure route highly relevant to real-world vector control tools such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS).
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