The evolving use of high-resolution MS (HRMS) across the pharmaceutical industry has seen its integrated application into both quantitative and qualitative assays. Through an American Association of Pharmaceutical Scientists (AAPS)/ American Society for Mass Spectrometry (ASMS) workshop, held at AAPS, key scientists from world pharma discussed the feasibility of this new paradigm shift through examples and visions for the future, assessing impact on drug discovery and drug development, as well as educating users new to HRMS in the field. This report details selected talks from the 2-day workshop, with particular emphasis on their impact, as well as personal conclusions around certain topics.
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http://dx.doi.org/10.4155/bio.12.22 | DOI Listing |
J Med Chem
January 2025
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
Since decades after temozolomide was approved, no effective drugs have been developed. Undoubtedly, blood-brain barrier (BBB) penetration is a severe issue that should be overcome in glioblastoma multiforme (GBM) drug development. In this research, we were inspired by linezolid through structural modification with several bioactive moieties to achieve the desired brain delivery.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, 52 Mei Hua East Road, Zhuhai, 519000, China.
Purpose: Cancer-associated fibroblasts (CAFs) are the primary stromal component of the tumor microenvironment in hepatocellular carcinoma (HCC), affecting tumor progression and post-resection recurrence. Fibroblast activation protein (FAP) is a key biomarker of CAFs. However, there is limited evidence on using FAP as a target in near-infrared (NIR) fluorescence imaging for HCC.
View Article and Find Full Text PDFJ Med Chem
January 2025
Medicinal Chemistry Department, Shanghai Haiyan Pharmaceutical Technology Co., Ltd., Pudong New Area, Shanghai 201203, China.
Synthetic lethality offers a robust strategy for discovering the next generation of precision medicine therapies tailored for molecularly defined patient populations. MAT2A inhibition is synthetically lethal in several cancers that exhibit a homozygous deletion of -methyl-5'-thioadenosine phosphorylase (MTAP). Herein, we report the identification of novel MAT2A inhibitors featuring a spiral ring to circumvent the C-N atropisomeric chirality utilizing structure-based drug design.
View Article and Find Full Text PDFAliment Pharmacol Ther
January 2025
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Background: Brain-gut behaviour therapies (BGBT) have gained widespread acceptance as therapeutic modalities for the management of disorders of gut-brain interaction (DGBI). However, existing treatment evaluation methods in the medical field fail to capture the specific elements of scientific rigour unique to behavioural trial evaluation.
Aims: To offer the first consensus on the development and testing of BGBT in DGBI.
J Chem Inf Model
January 2025
Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, Padova 35131, Italy.
During the last 20 years, the fragment-based drug discovery approach gained popularity in both industrial and academic settings due to its efficient exploration of the chemical space. This bottom-up approach relies on identifying high-efficiency small ligands (fragments) that bind to a target binding site and then rationally evolve them into mature druglike compounds. To achieve such a task, researchers rely on accurate information about the ligand binding mode, usually obtained through experimental techniques, such as X-ray crystallography or computer simulations.
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