Continuous collective analysis of chemical reactions.

The automated synthesis of small organic molecules from modular building blocks has the potential to transform our capacity to create medicines and materials. Disruptive acceleration of this molecule-building strategy broadly unlocks its functional potential and requires the integration of many new assembly chemistries. Although recent advances in high-throughput chemistry can speed up the development of appropriate synthetic methods, for example, in selecting appropriate chemical reaction conditions from the vast range of potential options, equivalent high-throughput analytical methods are needed.

Advances in antimicrobial orthopaedic devices and FDA regulatory challenges.

Implant-associated infections, caused by the formation of biofilms especially antibiotic resistant organisms, are among the leading causes of orthopaedic implant failure. Current strategies to combat infection and biofilm focus on either inhibiting bacterial growth or preventing bacterial adherence that could lead to biofilm creation. Despite research on developing numerous antimicrobial orthopaedic devices, to date, no robust solution has been translated to the clinic.

Molecular and genetic characterization of sex-linked orange coat color in the domestic cat.

The mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat color genes, there is no apparent homolog for in other mammals. We show that the is caused by a 5 kb deletion that leads to ectopic and melanocyte-specific expression of the ( ) gene.

Structure-Activity Relationship of Potent, Selective, and Orally Bioavailable Molecular Glue Degraders of CK1α.

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). With the aim of understanding and modulating neosubstrate specificity, we recently reported the discovery of SJ3149 (), a selective and potent molecular glue degrader of CK1α, that is active in multiple cancer cell lines. Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders.