One major barrier in the development of pancreas cancer therapeutics is the selective delivery of the drugs to their cellular targets. We have previously developed several sigma-2 ligands and reported the discovery of a component of the receptor for these ligands. Several sigma-2 ligands have been shown to trigger apoptosis in pancreas cancer cells. More importantly, sigma-2 ligands are internalized rapidly by the cancer cells and are capable of delivering other small-molecule therapeutics. Here we review sigma-2 ligands and conjugates as a potential novel therapy suitable for investigation in patients with pancreatic cancer.
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http://dx.doi.org/10.1016/j.surg.2012.05.014 | DOI Listing |
Chem Sci
December 2024
Institute of Advanced Materials, Wroclaw University of Science and Technology Wrocław Poland
Near-infrared (NIR) emitters with high two-photon absorption (2PA) cross-sections are of interest to enable imaging in the tissue transparency windows. This study explores the potential of DNA-stabilized silver nanoclusters (Ag -DNAs) as water-soluble two-photon absorbers. We investigate 2PA of four different atomically precise Ag -DNA species with far-red to NIR emission and varying nanocluster and ligand compositions.
View Article and Find Full Text PDFAnal Chem
December 2024
Instituto de Biomedicina y Genética Molecular, Unidad de Excelencia, University of Valladolid-CSIC, Valladolid 47003, Spain.
Lipid rafts are liquid-ordered domains in which specific enzymes and receptors are located. These membrane platforms play crucial roles in a variety of signaling pathways. Alterations in the lipid environment, such as those elicited by oxidative stress, can lead to important functional disruptions in membrane proteins.
View Article and Find Full Text PDFJ Prev Alzheimers Dis
November 2024
Anthony O. Caggiano, MD, PhD, Cognition Therapeutics, Inc., 2500 Westchester Avenue, Purchase, NY 10577,
Background: CT1812 is a first-in-class, sigma-2 receptor ligand, that prevents and displaces binding of amyloid beta (Aβ) oligomers. Normalization of quantitative electroencephalography (qEEG) markers suggests that CT1812 protects synapses from Aβ oligomer toxicity.
Objectives: Evaluate CT1812 impact on synaptic function using qEEG measurements.
Biochem Biophys Res Commun
December 2024
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, United States. Electronic address:
TMEM97, also known as the sigma-2 receptor, plays a crucial role as an endoplasmic reticular protein involved in various physiological processes such as wound healing, and cholesterol metabolism. Moreover, TMEM97 has been implicated in multiple human diseases including neurodegenerative disorders and cancers. Histatin peptides are endogenous peptides with diverse biological effects, including antimicrobial, immunomodulatory, and wound healing functions.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Universität Münster, Institut für Pharmazeutische und Medizinische Chemie, Corrensstraße 48, D-48149, Münster, Germany. Electronic address:
The σ receptor plays a key role in the regulation of various processes in the human body; it is involved in the development of neurodegenerative and neuropsychiatric diseases and is overexpressed in several human tumors rendering it an important target for potential drug candidates. In this project, spirocyclic σ receptor ligands with different substituents in 4- and 9-position were synthesized and investigated for their σ receptor affinity and selectivity over related targets. The σ affinity of the ligands was correlated with their lipophilicity (logD value) giving insight into their lipophilic ligand efficiency (LLE).
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