Advances in molecular biology and molecular genetics as well as major scientific breakthroughs in immunology and oncology have led to the rapid growth of biologic therapeutics. Their success has resulted in significant changes to virtually every step in the drug discovery and development process. Biologics are produced by living organisms, and screening libraries are generated by immunization or phage display. Lead optimization utilizes sophisticated protein engineering to improve drug-like properties and targeting specificity. The manufacturing process for biologics is complex and requires highly specialized facilities. Determination of pharmacology and safety must overcome the complications associated with species specificity. Initial clinical testing must proceed more slowly and carefully due to the limited predictive utility of preclinical data. In summary, the drug discovery and development process has been dramatically altered by biologic therapeutics and will continue to evolve with the introduction of messenger RNA-based therapeutics and the application of artificial intelligence.
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http://dx.doi.org/10.1146/annurev-pharmtox-061724-080811 | DOI Listing |
ChemMedChem
January 2025
Charles University Faculty of Pharmacy in Hradec Kralove: Univerzita Karlova Farmaceuticka fakulta v Hradci Kralove, Dept. of pharmaceutical chemistry and pharmaceutical analysis, Ak. Heyrovskeho 1203/8, 50003, Hradec Kralove, Czech Republic, CZECHIA.
Tuberculosis remains a leading global health threat, exacerbated by the emergence of multi-drug-resistant strains. The search for novel therapeutic agents is critical in addressing this challenge. This review systematically summarizes the potential of oxadiazole derivatives as promising candidates in antimycobacterial drug discovery.
View Article and Find Full Text PDFJ Cell Sci
January 2025
National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology and State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Rd, Qingdao, 266237, People's Republic of China.
Glycosaminoglycans (GAGs), as animal polysaccharides, are linked to proteins to form various types of proteoglycans. Bacterial GAG lyases are not only essential enzymes that spoilage bacteria use for the degradation of GAGs, but also valuable tools for investigating the biological function and potential therapeutic applications of GAGs. The ongoing discovery and characterization of novel GAG lyases has identified an increasing number of lyases suitable for functional studies and other applications involving GAGs, which include oligosaccharide sequencing, detection and removal of specific glycan chains, clinical drug development and the design of novel biomaterials and sensors, some of which have not yet been comprehensively summarized.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice.
View Article and Find Full Text PDFChem Sci
January 2025
Chemical Biology and Drug Discovery, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University Universiteitsweg 99 3584 CG Utrecht The Netherlands
Sialyltransferases (ST) are key enzymes found in, among others, mammals and bacteria that are responsible for producing sialylated glycans, which play critical roles in human health and disease. However, chemical tools to study sialyltransferases have been limited to non-covalent inhibitors and probes that do not allow isolation and profiling of these important enzymes. Here we report a new class of covalent affinity-based probes (AfBP) for ST by using ligand-directed chemistry (LDchem).
View Article and Find Full Text PDFFront Toxicol
January 2025
Digital In Vivo Alliance (DIVA), Redwood City, CA, United States.
The adoption of digital measures in pharmaceutical research and development (R&D) presents an opportunity to enhance the efficiency and effectiveness of discovering and developing new therapeutics. For clinical measures, the Digital Medicine Society's (DiMe) V3 Framework is a comprehensive validation framework that encompasses verification, analytical validation, and clinical validation. This manuscript describes collaborative efforts to adapt this framework to ensure the reliability and relevance of digital measures for a preclinical context.
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