canSAR 2024-an update to the public drug discovery knowledgebase.

canSAR (https://cansar.ai) continues to serve as the largest publicly available platform for cancer-focused drug discovery and translational research. It integrates multidisciplinary data from disparate and otherwise siloed public data sources as well as data curated uniquely for canSAR.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques.

Assessing Alkene Reactivity toward Cytochrome P450-Mediated Epoxidation through Localized Descriptors and Regression Modeling.

The prediction of sites of epoxidation by cytochrome P450s during metabolism is particularly important in drug design, as epoxides are capable of alkylating biological macromolecules. Reliable methods are needed to quantitatively predict P450-mediated epoxidation barriers for inclusion in high-throughput screening campaigns alongside protein-ligand docking. Utilizing the fractional occupation number weighted density (FOD) and orbital-weighted Fukui index () as descriptors of local reactivity and a data set of 36 alkene epoxidation barriers computed with density functional theory (DFT), we developed and validated a multiple linear regression model for the reliable estimation of epoxidation barriers using only substrate structures as input.

Calculated oxidation potentials predict reactivity in Baeyer-Mills reactions.

Azobenzenes are widely used as dyes and photochromic compounds, with the Baeyer-Mills reaction serving as the most common method for their preparation. This transformation is often plagued by low yields due to the formation of undesired azoxybenzene. Here, we explore electronic effects dictating the formation of the azoxybenzene side-product.

A Redox Isomerization Strategy for Accessing Modular Azobenzene Photoswitches with Near Quantitative Bidirectional Photoconversion.

Photoswitches capable of accessing two geometric states are highly desirable, especially if their design is modular and incorporates a pharmacophore tethering site. We describe a redox isomerization strategy for synthesizing -formylazobenzenes from -nitrobenzyl alcohol. The resulting azo-aldehydes can be readily converted to photoswitchable compounds with excellent photophysical properties using simple hydrazide click chemistry.

The Suzuki reaction in aqueous media promoted by P, N ligands.

The synthesis and structure of palladium complexes of trisubstituted PTA derivatives, PTA(R3), are described. Water-soluble phosphine ligands 1,3,5-triaza-7-phosphaadmantane (PTA), tris(aminomethyl)phosphine trihydrobromide, tri(aminomethyl) phosphine, 3,7-dimethyl-1,5,7-triaza-3-phosphabicyclo[3,3,1]nonane (RO-PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.