Cysteine cathepsins are proteases critical in physiopathological processes and show potential as targets or biomarkers for diseases and medical conditions. The 11 members of the cathepsin family are redundant in some cases but remarkably independent of others, demanding the development of both pan-cathepsin targeting tools as well as probes that are selective for specific cathepsins with little off-target activity. This review addresses the diverse design strategies that have been employed to accomplish this tailored selectivity among cysteine cathepsin targets and the imaging modalities incorporated. The power of these diverse tools is contextualized by briefly highlighting the nature of a few prominent cysteine cathepsins, their involvement in select diseases, and the application of cathepsin imaging probes in research spanning basic biochemical studies to clinical applications.
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http://dx.doi.org/10.1039/d1ob00225b | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.
Entomopathogenic fungi play a critical role in regulating insect populations, and representative species from the and genera have been developed as eco-friendly biocontrol agents for managing agricultural insect pests. Relative to the advances in understanding antifungal immune responses in , knowledge of how fungi evade insect immune defenses remains limited. In this study, we report the identification and characterization of a virulence-required effector Fkp1 in .
View Article and Find Full Text PDFJ Med Chem
January 2025
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.
View Article and Find Full Text PDFFront Neurol
December 2024
Nordic Bioscience, Herlev, Denmark.
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). There is a significant delay in diagnosing MS as the symptoms and tests overlap with other diseases. Blood-based biomarkers, which quantify fragments of proteins involved in MS pathophysiology, have the potential as diagnostic biomarkers.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Sustainable Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Leuven 3000, Belgium.
Cruzipain (CZP) is an essential cysteine protease of , the etiological agent of Chagas disease, and a promising druggable target. To date, no CZP inhibitors have reached clinical use, with research efforts mostly hampered by insufficient potency, limited target selectivity or lack of bioactivity translation from the isolated enzyme to the parasite in cellular environments. In this study, we report the design of , a 1,2,3-triazole-based targeted covalent inhibitor with nanomolar potency (IC = 28 nM) and null inhibition of human cathepsin L.
View Article and Find Full Text PDFTetrahedron
February 2025
Department of Chemistry and Biochemistry, Baylor University, One Bear Place, No. 97348, Waco, Texas 76798-7348, United States.
Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels.
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