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KRAS inhibitors: resistance drivers and combinatorial strategies.
Trends Cancer
December 2024
Charité - Universitätsmedizin Berlin, Institute of Pathology, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
In 1982, the RAS genes HRAS and KRAS were discovered as the first human cancer genes, with KRAS later identified as one of the most frequently mutated oncogenes. Yet, it took nearly 40 years to develop clinically effective inhibitors for RAS-mutant cancers. The discovery in 2013 by Shokat and colleagues of a druggable pocket in KRAS paved the way to FDA approval of the first covalently binding KRAS inhibitors, sotorasib and adagrasib, in 2021 and 2022, respectively.
View Article and Find Full Text PDFAntisense oligonucleotides-based approaches for the treatment of multiple myeloma.
Int J Biol Macromol
December 2024
Faculty of Medical Engineering, National University of Science and Technology Politehnica Bucharest, Gheorghe Polizu 1-7, 011061 Bucharest, Romania; Advanced Polymer Materials Group, University Politehnica of Bucharest, Gheorghe Polizu 1-7, 011061 Bucharest, Romania; ebio-Hub Research Centre, University Politehnica of Bucharest-Campus, Iuliu Maniu 6, 061344 Bucharest, Romania. Electronic address:
Multiple myeloma (MM), a hematological malignancy which affects the monoclonal plasma cells in the bone marrow, is in rising incidence around the world, accounting for approximately 2 % of newly diagnosed cancer cases in the US, Australia, and Western Europe. Despite the progress made in the last few years in the available therapeutic options (e.g.
View Article and Find Full Text PDFAccelerating antiviral drug discovery: early hazard detection with a dual zebrafish and cell culture screen of a 403 compound library.
Arch Toxicol
December 2024
Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR, 97333, USA.
The constant emergence of new viral pathogens underscores the need for continually evolving, effective antiviral drugs. A key challenge is identifying compounds that are both efficacious and safe, as many candidates fail during development due to unforeseen toxicity. To address this, the embryonic zebrafish morphology, mortality, and behavior (ZBE) screen and the SYSTEMETRIC® Cell Health Screen (CHS) were employed to evaluate the safety of 403 compounds from the Cayman Antiviral Screening Library.
View Article and Find Full Text PDFMethodology for Safe and Secure AI in Diabetes Management.
J Diabetes Sci Technol
December 2024
CyberActa, Sudbury, MA, USA.
The use of artificial intelligence (AI) in diabetes management is emerging as a promising solution to improve the monitoring and personalization of therapies. However, the integration of such technologies in the clinical setting poses significant challenges related to safety, security, and compliance with sensitive patient data, as well as the potential direct consequences on patient health. This article provides guidance for developers and researchers on identifying and addressing these safety, security, and compliance challenges in AI systems for diabetes management.
View Article and Find Full Text PDFEvaluation of ATP-Bioluminescence Detection as a Supportive Technology for Bioburden and Sterility Testing Processes.
PDA J Pharm Sci Technol
December 2024
CDER/OPQ/Office of Pharmaceutical Quality and Research-DPQRVI, Silver Spring, MD.
A challenge facing the biomanufacturing industry is the lengthy timeline for quality control testing that delays critical go/no-go decision making for the rapid release of drug products. The recommended USP methods for bioburden and sterility testing are surface-spread plating method and direct inoculation method, respectively. These compendial methods are reliable; however, results take approximately 5-7 days for bioburden testing (USP< 61>) and no less than 14 days for sterility testing (USP < 71>).
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