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Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy.
J Nucl Med
December 2024
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China;
Given the variability in the effectiveness of immune checkpoint blocking therapy among patients and tumor types, development of noninvasive methods for longitudinal assessment of immune cell function and early tumor response is crucial for precision immunotherapy. CD137 (4-1BB), a marker of activated T cells, plays a significant role in immunotherapy. However, its potential as an imaging biomarker for activated T cells in the tumor microenvironment has not been explored.
View Article and Find Full Text PDFCobalt-Catalyzed (3 + 2) Cycloaddition of Cyclopropene-Tethered Alkynes: Versatile Access to Bicyclic Cyclopentadienyl Systems and Their CpM Complexes.
ACS Catal
August 2024
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS) and Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Low-valent cobalt complexes can promote intramolecular (3 + 2) cycloadditions of alkyne-tethered cyclopropenes to provide bicyclic systems containing highly substituted cyclopentadienyl moieties with electronically diverse functional groups. The adducts can be easily transformed into new types of CpRh(III) and CpIr(III) complexes, which show catalytic activity in several relevant transformations. Preliminary computational (DFT) and experimental studies provide relevant information on the mechanistic peculiarities of the cobalt-catalyzed process and allow us to rationalize its advantages over the homologous rhodium-promoted reaction.
View Article and Find Full Text PDFProduct Selectivity in Baeyer-Villiger Monooxygenase-Catalyzed Bacterial Alkaloid Core Structure Maturation.
J Am Chem Soc
June 2024
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Natural Product Biotechnology, Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus E8.1, 66123 Saarbrücken, Germany.
Baeyer-Villiger monooxygenases (BVMOs) play crucial roles in the core-structure modification of natural products. They catalyze lactone formation by selective oxygen insertion into a carbon-carbon bond adjacent to a carbonyl group (Baeyer-Villiger oxidation, BVO). The homologous bacterial BVMOs, BraC and PxaB, thereby process bicyclic dihydroindolizinone substrates originating from a bimodular nonribosomal peptide synthetase (BraB or PxaA).
View Article and Find Full Text PDFMacrocycles and macrocyclization in anticancer drug discovery: Important pieces of the puzzle.
Eur J Med Chem
March 2024
Laboratory for Food and Medicine Homologous Natural Resources Development and Utilization, Belgorod College of Food Sciences, Dezhou University, Dezhou, 253023, China; State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China. Electronic address:
Increasing disease-related proteins have been identified as novel therapeutic targets. Macrocycles are emerging as potential solutions, bridging the gap between conventional small molecules and biomacromolecules in drug discovery. Inspired by successful macrocyclic drugs of natural origins, macrocycles are attracting more attention for enhanced binding affinity and target selectivity.
View Article and Find Full Text PDFStructural role of K224 in taniborbactam inhibition of NDM-1.
Antimicrob Agents Chemother
February 2024
Department of Medicine, Division of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Taniborbactam (TAN; VNRX-5133) is a novel bicyclic boronic acid β-lactamase inhibitor (BLI) being developed in combination with cefepime (FEP). TAN inhibits both serine and some metallo-β-lactamases. Previously, the substitution R228L in VIM-24 was shown to increase activity against oxyimino-cephalosporins like FEP and ceftazidime (CAZ).
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