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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: models/Detail_model.php
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Background: b-AP15/VLX1570 are small molecule inhibitors of the ubiquitin specific peptidase 14 (USP14) and ubiquitin carboxyl-terminal hydrolase 5 (UCHL5) deubiquitinases (DUBs) of the 19S proteasome. b-AP15/VLX1570 have been shown to be cytotoxic to cells resistant to bortezomib, raising the possibility that this class of drugs can be used as a second-line therapy for treatment-resistant multiple myeloma. Limited information is available with regard to potential resistance mechanisms to b-AP15/VLX1570.
Results: We found that b-AP15-induced cell death is cell-cycle dependent and that non-cycling tumor cells may evade b-AP15-induced cell death. Such non-cycling cells may re-enter the proliferative state to form colonies of drug-sensitive cells. Long-term selection of cells with b-AP15 resulted in limited drug resistance (~2-fold) that could be reversed by buthionine sulphoximine, implying altered glutathione (GSH) metabolism as a resistance mechanism. In contrast, drug uptake and overexpression of drug efflux transporters were found not to be associated with b-AP15 resistance.
Conclusions: The proteasome DUB inhibitors b-AP15/VLX1570 are cell cycle-active. The slow and incomplete development of resistance towards these compounds is an attractive feature in view of future clinical use.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804958 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223807 | PLOS |
ACS Chem Biol
December 2024
UNC Eshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Tudor domains are histone readers that can recognize various methylation marks on lysine and arginine. This recognition event plays a key role in the recruitment of other epigenetic effectors and the control of gene accessibility. The Tudor-containing protein family contains 42 members, many of which are involved in the development and progression of various diseases, especially cancer.
View Article and Find Full Text PDFMol Cell Biochem
December 2024
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Henan Xinxiang, 453003, People's Republic of China.
To investigate the promoting effect of extracellular vesicles derived from myocardial cells (CM-EVs) on the reprogramming of cardiac fibroblasts (CFs) into cardiomyocyte-like cells (iCMs) and their therapeutic effect on myocardial infarction (MI) in rats. Cell experiments: The differential adhesion method was used to obtain Sprague Dawley (SD) suckling rat CFs and cardiomyocytes (CMs), while the ultracentrifugation method was used to obtain CM-EVs. Transmission electron microscopy and nanoparticle tracking technology were used to analyze and determine the morphology and particle size of CM-EVs.
View Article and Find Full Text PDFLangmuir
December 2024
School of Materials, Sun Yat-sen University, Shenzhen 518107, China.
Hydrogen sulfide (HS), carbonyl sulfide (COS), and dimethyl sulfide (DMS) are the primary sulfur compounds found in seawater, which cause pitting corrosion on the oxide passivation film of titanium, known as "the marine metals". In this study, density functional theory (DFT) was used to analyze the adsorption and surface electronic properties of these three small molecules on the anatase TiO(101) surface. The analysis was conducted through adsorption energy, work function, Mulliken charge population, and density of states (DOS).
View Article and Find Full Text PDFExpert Opin Ther Pat
December 2024
Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Introduction: Approximately one-third of all AML patients have a mutation in the Fms-like tyrosine kinase 3 () gene, which is associated with a poor prognosis in these individuals. The 2017 approval of midostaurin, the first FLT3 inhibitor, spurred extensive development of more potent and selective inhibitors with an improved safety profile.
Areas Covered: This review analyzes patent inventions for the treatment of AML using FLT3 inhibitors, covering developments from the earliest to the most recent, disclosed in 2024.
Bioconjug Chem
December 2024
Philochem AG, R&D Department, CH-8112 Otelfingen, Switzerland.
OncoFAP is an ultrahigh affinity ligand of fibroblast activation protein (FAP), a tumor-associated antigen overexpressed in the stroma of the majority of solid tumors. OncoFAP has been previously implemented as a tumor-homing moiety for the development of small molecule drug conjugates (SMDCs). In the same context, the glycine--proline dipeptide was included with the aim to selectively undergo cleavage only in the presence of the target FAP, triggering the consequent release of the cytotoxic payload in the tumor microenvironment.
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