Scaffold-based Drug Design

Founded in 2001, Plexxikon is one of the only companies to employ X-ray co-crystallography early and continuously in the drug discovery process. Our medicinal chemists approach drug design with scalpel-like precision, using their knowledge of the detailed interactions of protein targets to design our small molecules. We use X-ray co-crystallography as a screening method to discover and exploit uncharted chemical space for novel scaffolds. We focus only on scaffolds with the greatest binding efficacy and chemical suitability, that can retain their binding positions throughout chemical exploration.

Plexxikon is one of the only companies to employ X-ray co-crystallography early and continuously in the drug discovery process.
 

Once a validated scaffold is in hand, we apply a modular, anchor-and-grow design strategy to explore different mechanisms of inhibition, ensuring each round of chemistry yields major gains in potency, selectivity, and/or pharmaceutical properties. In our experience, simple tweaking of existing chemotypes can’t resolve a flawed design. Instead, we rely on rational engineering of novel scaffolds, which generates competitively differentiated products. This “scaffold-based drug design” (SBDD) method has led to the discovery of novel agents obstructing disease-specific conformations of high-value drug targets. Our two commercial products, vemurafenib (Zelboraf®) and pexidartinib (TURALIO®), are both first-in-class small molecule cancer drugs, exemplary of the success and promise of SBDD.

plexxikon scaffold-based drug design image

Selected Scientific Publications

Our scientific and clinical findings have been presented and published in peer-reviewed forums, and a selection of these have been curated for reference.

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