Fragment Library Screening & Lead Discovery Services

Hit identification, hit to lead & lead optimization services

SARomics Biostructures' fragment screening, structure-based lead discovery, and lead optimization services offer access to our proprietary weak-affinity chromatography (WAC™) screening technology. Our services include:
  • Fragment screening & hit identification using WAC™ screening technology (proprietary fragment library or custom compound screening library)
  • Structure-based hit to lead and lead optimization services
  • Computational Chemistry services: pharmacophore and shape-based virtual screening services, scaffold hopping, design of screening library, QSAR analysis, and compound optimization
  • Biochemical and cell-based assay and in vitro ADME

Our hit-to-lead & lead optimization services are guided by protein
X-ray crystallographic analysis of the target structure in complex with the compounds of interest.

WAC™ is a robust and cost-efficient screening method. It
can be combined with biophysical screening techniques for hit identification and verification, such as thermal-shift assay (DSF), isothermal titration calorimetry (ITC), and protein NMR spectroscopy. SARomics Biostructures and our in-house partner Red Lead Discovery jointly own the commercial rights of the WAC™ screening technology.

Different drug discovery strategies can be applied depending on the availability of structural information. This is briefly discussed in our
recent blog post and with more details on our technology pages. You may also contact us to discuss the details of our services and your project.

For details of the services, please follow the links below.
At the center of our fragment screening & lead discovery services is the high throughput (2000-3000 cmpds/week) proprietary weak-affinity chromatography (WAC™) screening technology, which provides high-quality data and has been validated against NMR spectroscopy and X-ray crystallography.
Our fragment library contains a collection of 1300 low-MW (<220) MedChem-friendly compounds (also available as neat samples, DMSO and DMSO-d6 solutions), designed to be general-purpose (not target-directed) covering diverse chemical space. Custom compound libraries can also be run.
Computation chemistry is an integral part of structure-based lead discovery. Our team has gathered extensive experience in computational chemistry and may provide a wide range of services, including:
  • Virtual screening services
  • Pharmacophore and shape-based virtual screening
  • Ligand-based drug design, etc.

Basics of WAC™ screening technology

WAC™ screening technology is the primary compound screening method used within our lead discovery services program. It is based on covalent immobilization of the protein target on a standard high-performance liquid chromatography (HPLC) column. A solution of small molecular weight fragments or larger compounds is injected into the column. During elution, the fragments with a higher affinity for the protein will stay on the column longer than those with a low affinity. The fragments can be conveniently detected using mass- or UV spectrometry. This method is an efficient and lower-cost choice compared to other biophysical screening methods used for compound screening, e.g., X-ray crystallography, protein NMR spectroscopy, or isothermal titration calorimetry (ITC).

After the initial hit identification,
protein NMR spectroscopy or X-ray crystallography can be used to gain additional insights into the details of the interactions of a compound with the protein. Ligand efficiency and ligand binding energy may also be estimated to guide the hit-to-lead and lead optimization processes.

The commercial rights of the WAC™ screening technology
are jointly owned by SARomics Biostructures and our in-house partner Red Glead Discovery.