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The flavin-containing monooxygenases (FMOs) metabolize a broad range of therapeutics. Consisting of five gene products in humans (FMO1-5), the different FMO family members exhibit pronounced tissue- and temporal-specific expression patterns. Substantial interindividual differences are also observed, and the inability to modulate with exogenous agents is consistent with an important role for genetic variation. Several rare FMO3 alleles causative for trimethylaminuria have been well characterized. However, the identification and characterization of functional FMO1-5 polymorphisms has been more recent. Although none of these polymorphisms has been associated with an adverse drug reaction, the continued broadening of our therapeutic armamentarium makes such an event likely in the future. Furthermore, at least one example has been reported for a direct association between FMO3 polymorphism and therapeutic efficacy. Thus, it is anticipated that knowledge regarding functionally-relevant FMO genetic variability will become increasingly important for making drug development and patient therapeutic choices.
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http://dx.doi.org/10.2217/14622416.6.8.807 | 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 PDFKorean J Physiol Pharmacol
September 2025
Department of Endocrinology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China.
The progression of renal fibrosis is difficult to reverse, and Poria cocos, one of the main components of Wenyang Zhenshuai Granules, has been shown to be crucial to the development of the epithelial-mesenchymal transition (EMT). This study aimed to examine the molecular mechanism by which Poricoic Acid A (PAA) inhibited the advancement of EMT in renal tubular epithelial (RTE) cells. The protein levels of sprouty RTK signaling antagonist 2 (SPRY2) extracellular regulated protein kinases (ERK), and p-ERK were measured.
View Article and Find Full Text PDFJ Pept Sci
October 2025
Institute of Technology, University of Tartu, Tartu, Estonia.
The development of therapeutic small interfering RNAs (siRNAs) has lately gained significant momentum due to their ability to silence genes in a highly specific manner. The main obstacle withholding the wider translation of siRNA-based drug modalities is their limited half-life and poor bioavailability, especially in extra-hepatic tissues. Consequently, various drug delivery systems (DDSs) have been developed to improve the delivery of siRNAs, including short delivery peptides called cell-penetrating peptides (CPPs).
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Henan Engineering Laboratory of Pest Biological Control/College of Plant Protection, Henan Agricultural University, Zhengzhou 450046, People's Republic of China.
Henosepilachna vigintioctopunctata represents a significant economic pest, typically controlled through the use of chemical insecticides. The introduction of RNA interference (RNAi) technology has opened new avenues for biopesticide development, leading to the identification of various genes that are crucial for the growth and development of insects. However, the efficient screening of target genes in H.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China. Electronic address:
The extensive use of highly toxic and residual pesticides has a significant negative impact on agricultural production and the ecological environment. The development of new green antiviral agents has become a major demand for ensuring the development of green ecological agriculture. Indole alkaloids are widely present in nature and have diverse biological activities.
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