The Twin Cities is home to over 40 international grocers, and they deserve your dollars, too.

Data collected from scholars across twenty-three countries over the past decade (2010–2019) reveals a 40% decrease in financial support for medicinal chemistry projects. The decline is especially notable among projects focused on small organic molecules. This drop in grants indicates a troubling trend that could jeopardize future drug development by undermining research in this crucial field. The reduction in funding not only affects ongoing research but also threatens the education and training of future medicinal chemists, potentially leading to a shortage of skilled professionals in the pharmaceutical industry. To counteract this negative trend, it is imperative for funding agencies, the pharmaceutical sector, and government bodies to take immediate action. Strengthening financial support is essential to sustain innovation in drug development and ensure the continued advancement of medicinal chemistry as a vital academic and practical discipline.

Published research on topics of current scientific interest.

Researchers facing

The 2025 Gordon Research Conference on High Throughput Chemistry and Chemical Biology will be held in New London, New Hampshire. Apply today to reserve your spot.

Scientists at the National Institutes of Health have been told the communications pause announced by the Trump Administration earlier this week includes a pause on all purchasing, including supplies f...

People with immune system health problems continue to take precautions against COVID-19 five years into the pandemic.

In an era of rapid scientific advancement, the need for engaging educational tools is critical. DEGRADATOR, a 2D computer game, bridges this gap by immersing players in the ubiquitin-proteasome system...

ALT: a wrestler with the name steveson on his back is jumping in the air

Openings for PhD students and postdocs will be advertized here

Abstract. The Chemical Probes Portal (www.chemicalprobes.org) is a free, public resource, based on expert-reviews, that supports the assessment, selection

Histone lysine lactylation (Kla) regulates inflammatory gene expression in activated macrophages and mediates the polarization of inflammatory (M1) to reparative (M2) macrophages. However, the molecular mechanisms and key protein players involved in Kla-mediated transcriptional changes are unknown. As Kla is structurally similar to lysine acetylation (Kac), which is bound by bromodomains, we hypothesized that bromodomain-containing proteins bind histone Kla. Here, we screened 28 recombinantly expressed bromodomains for binding to histone Kla peptides via AlphaScreen assays. TRIM33 was the sole bromodomain tested that bound histone Kla peptides. TRIM33 attenuates inflammatory genes during late-stage macrophage activation; thus, TRIM33 provides a potential link between histone Kla and macrophage polarization. Orthogonal biophysical techniques, including isothermal titration calorimetry and protein-detected nuclear magnetic resonance, confirmed the submicromolar binding affinity of the TRIM33 bromodomain to both Kla and Kac histone post-translational modifications. Sequence alignments of human bromodomains revealed a unique glutamic acid residue within the TRIM33 binding pocket that we found confers TRIM33 specificity for binding Kla compared with other bromodomains. Molecular modeling of interactions of Kla with the TRIM33 bromodomain binding pocket and site-directed mutagenesis of glutamic acid confirmed the critical role of this residue in the selective recognition of Kla by TRIM33. Collectively, our findings implicate TRIM33, a bromodomain-containing protein, as a novel reader of histone Kla, potentially bridging the gap between histone Kla and macrophage polarization. This study enhances our understanding of the regulatory role of histone Kla in macrophage-mediated inflammation and offers insights into the underlying structural and biophysical mechanisms.

Stabilization of cereblon (CRBN)/neosubstrate complexes with molecular glues followed by degradation of those neosubstrates is an emerging strategy in drug discovery with compelling potential to target certain proteins that were previously considered to be undruggable. In this context, the discovery of novel CRBN ligands is an important area of ongoing research that holds promise to expand the scope of proteins that can be targeted through this mode of action. Herein, we describe the synthesis and evaluation of CRBN ligands featuring heteroaryl glutarimide and dihydrouracil scaffolds. We identified a subset of heteroaryl glutarimides exhibiting potent CRBN binding and increased chemical stability in cell culture media compared with traditional immunomodulatory drugs (IMiDs). This indicates that the scaffolds described herein could become useful starting points for the discovery of novel molecular glue degraders.