They key objective of the hit-to-lead phase is to rapidly identify multiple hit series that have the best potential to develop into drug-like leads. At X-Chem, this process is accelerated by having a selectivity profile and an early understanding of residence time and structure-activity relationships (SARs) generated directly from the PartnerDEX or OpenDEX screening data package. In addition, we employ in silico and (where appropriate) in vitro DMPK profiling to help select hits and help define the optimization strategy.

X-Chem has a successful track record of capitalizing on the richness of DEL output to drive rapid optimization and efficiently progress hit-to-lead projects in a timely manner:

  • X-Chem’s experienced teams identify potential liabilities in hit molecules, design well-suited screening cascades, and create improved structures that resolve physicochemical, toxicological and metabolic issues, while maintaining key target interactions.
  • In silico profiling of compounds (SBDD, MMPA, etc.) helps to prioritize medicinal chemistry strategies and facilitates potency/clearance/selectivity optimization or scaffold-hopping techniques, which can be used to generate new hit series with improved properties.
  • A wide range of in vitro and in vivo DPMK assays are available through our network of partners, allowing rapid hit profiling.

Rigorous early assessment of the available hits has a major impact on the time required for optimization. Even for challenging targets, X-Chem has a track record of identifying high-quality hits. These hits can be coupled with X-Chem’s expertise in effectively driving hit-to-lead and lead-to-candidate identification.

X-Chem’s capabilities include medicinal chemistry, custom synthesis and scale-up process chemistry supporting lead optimization through candidate identification. Backed by a widely published scientific leadership team with over 20 years of experience in major pharma driving drug discovery, results include:

  • >100 patents
  • 17 compounds advanced to IND-enabling tox
  • 7 compounds reaching Phase I or beyond