Identification and characterization of ternary complexes consisting of FKBP12, MAPRE1 and macrocyclic molecular glues.

Many disease-relevant and functionally well-validated targets are difficult to drug. Their poorly defined 3D structure without deep hydrophobic pockets makes the development of ligands with low molecular weight and high affinity almost impossible. For these targets, incorporation into a ternary complex may be a viable alternative to modulate and in most cases inhibit their function.

A 'One-Shot' strategy for preparative chiral sub/supercritical fluid chromatography with chiroptical detection accelerates purification and enhances characterization for drug discovery.

The advantages of a streamlined SFC chiral workflow for preparative chromatographic resolution of the enantiomers of investigational new compounds for pharmaceutical discovery on 10-20 mg scale with on-line chiroptical detection is described. The workflow has been designed to supply milligram amounts of enantiopure material using a universal gradient elution approach. Implementation of a faster and more labor efficient chiral purification workflow was the primary objective, with the secondary objective being an on-line collection of stereochemical information for separated enantiomers with the return of weighed compounds with acceptable purity.

JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRAS for the Treatment of Solid Tumors.

Rapid emergence of tumor resistance via RAS pathway reactivation has been reported from clinical studies of covalent KRAS inhibitors. Thus, inhibitors with broad potential for combination treatment and distinct binding modes to overcome resistance mutations may prove beneficial. JDQ443 is an investigational covalent KRAS inhibitor derived from structure-based drug design followed by extensive optimization of two dissimilar prototypes.

Automated chiral method screening - Evaluation of generated chromatographic data sets to further optimize screening efficiency.

We set up an automated screening process to routinely test 10 chiral supercritical fluid chromatography (SFC) methods - five columns combined with two co-solvents - as part of a chiral separation lab workflow. Proprietary software tools enabled automated method screening of racemates, parallel evaluation of the resulting chromatograms for enantiomer separation and report generation. This process is largely automated and resulted in an efficient and reliable lab process with a minimum requirement for human intervention.

Comparison of liquid and supercritical fluid chromatography mobile phases for enantioselective separations on polysaccharide stationary phases.

Analysis and production of enantiomerically pure compounds is a major topic of interest when active pharmaceutical ingredients are concerned. Enantioselective chromatography has become a favourite both at the analytical and preparative scales. High-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) are dominating the scene and are often seen as complementary techniques.