Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.4c01345 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Optimization of Potent and Selective Cyclohexyl Acid ERAP1 Inhibitors Using Structure- and Property-Based Drug Design.
ACS Med Chem Lett
December 2024
National Center for Scientific Research "Demokritos", Agia Paraskevi, Attiki 15341, Greece.
Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the -terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation onto the cell surface, driving the activation of adaptive immune responses. In cancer, overtrimming of mature antigenic peptides can reduce cytotoxic T-cell responses, and ERAP1 can generate self-antigenic peptides which contribute to autoimmune cellular responses. Therefore, modulation of ERAP1 activity has potential therapeutic indications for cancer immunotherapy and in autoimmune disease.
View Article and Find Full Text PDFProperty-based optimisation of PROTACs.
RSC Med Chem
November 2024
Oncology R&D, AstraZeneca 1 Francis Crick Avenue Cambridge CB2 0AA UK
PROTACs are an emerging therapeutic approach towards targeted protein degradation. This article examines the leading examples of this modality that are in clinical development through the prism of their physicochemical properties. In particular, the optimisation of the various components of PROTACs together with the difficulties faced by medicinal chemists seeking to achieve oral bioavailability in this challenging space are outlined.
View Article and Find Full Text PDFHighly Effective Biocides against Reveal New Mechanistic Insights Across Gram-Negative Bacteria.
ACS Infect Dis
November 2024
Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
is a major nosocomial pathogen that persists in healthcare settings despite rigorous disinfection protocols due to intrinsic mechanisms conferring resistance. We sought to systematically assess cationic biocide efficacy against this pathogen using a panel of multidrug-resistant clinical isolates. Our studies revealed widespread resistance to commercial cationic disinfectants that are the current standard of care, raising concerns about their efficacy.
View Article and Find Full Text PDFDeuterated reagents in multicomponent reactions to afford deuterium-labeled products.
Beilstein J Org Chem
September 2024
Department of Chemistry and Biochemistry, College of Science, University of Arizona, Tucson, Arizona, 85721, USA.
The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D]-aldehydes and [D]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a limiting metabolic soft-spot via use of [D]-aldehydes.
View Article and Find Full Text PDFDiscovery and Optimization of N-Heteroaryl Indazole LRRK2 Inhibitors.
J Med Chem
September 2024
Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson's disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of unknown origin, so structural diversity in subsequent chemical matter was prioritized.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!