The science of drug discovery involves multiparameter optimization of molecular structures through iterative design-make-test cycles. For medicinal chemistry library synthesis, traditional workflows involve the isolation of each individual compound, gravimetric quantitation, and preparation of a standard concentration solution for biological assays. In this work, we explore ways to expedite this process by testing unpurified library mixtures using a combination of mass spectrometry-based assays for affinity selection and microsomal metabolic stability.
View Article and Find Full Text PDFBackground: Less than 1% of studies on child and adolescent health report the involvement of adolescents in health research. This is attributed to barriers experienced by researchers and adolescents in the engagement process. To address this under-involvement of adolescents, we first need a better understanding of the factors that hinder adolescent involvement in health research.
View Article and Find Full Text PDFInterests in covalent drugs have grown in modern drug discovery as they could tackle challenging targets traditionally considered "undruggable". The identification of covalent binders to target proteins typically involves directly measuring protein covalent modifications using high-resolution mass spectrometry. With a continually expanding library of compounds, conventional mass spectrometry platforms such as LC-MS and SPE-MS have become limiting factors for high-throughput screening.
View Article and Find Full Text PDFA currently overlooked application of the latent curve model (LCM) is its use in assessing the consequences of development patterns of change-that is as a predictor of distal outcomes. However, there are additional complications for appropriately specifying and interpreting the distal outcome LCM. Here, we develop a general framework for understanding the sensitivity of the distal outcome LCM to the choice of time coding, focusing on the regressions of the distal outcome on the latent growth factors.
View Article and Find Full Text PDFDespite an increased recognition of the right of adolescents to be involved in decisions that affect them, young people continue to be under-involved in health research. One of the reasons is a lack of awareness among researchers on the current evidence base around the benefits of involving adolescents. To address this, we conducted an umbrella review to synthesize the evidence on the positive impacts of adolescent involvement in health research.
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