Drug Discovery Strategies

The general process of lead identification includes two essential steps:
1. Fragment screening & hit generation
2. Hit expansion, lead generation and optimization

At the start we need to examine the information available for the target in question. Based on it, we can design a strategy and a plan the project.

Possible strategies
On the image below along the imaginary X-axis we have two options - protein structure known and protein structure unknown. The options along the Y-axis there are - ligand structure known and unknown ligand structure. Depending on the combination of these options, we may follow different strategies.
The most beneficial blue quadrant shows what can be done when both protein and ligand structures are known. Green is the next best, when protein structure is known, but no ligand structure, etc.

A structure will always accelerate the drug discovery project!

Fragment Screening and Hit Identification

For initial hit generation we primarily use our proprietary weak affinity chromatography (WAC™) technology. The screening can be made using our proprietary fragment library (fragment-based drug design, FBDD) or clients library.

Compound activity assays are performed using assay capabilities of our close partner
Red Glead. We may also assess the binding of the identified compounds using biophysical methods, like Nuclear Magnetic Resonance (protein NMR), thermal-shift assay or X-ray crystallography.

If no experimental structure available for the target, SARomics Biostructures offers
gene-to-structure services. In this case the protein is cloned, expressed, purified and crystallized (details of the crystallography process) and its X-ray crystallographic structure is determined at the company.

Hit Expansion and Lead Generation

When the three-dimensional structure of a protein-ligand complex is known, further optimization of the chemistry and physical-chemistry characteristics of the compounds is substantially easier. Multiple protein-ligand complexes can provide detailed mapping of the binding site, which in turn is used in the design of new compounds. Optimization of ligand structure normally requires several cycles. The result may be a series of compounds, which after further optimization and tests will generate a lead molecule. The process of hit expansion and lead generation is run in close collaboration with Red Glead Discovery, our in-house partner in drug discovery and design.

SARomics Biostructures
Integrated drug discovery services are usually adapted to the needs of each project and the requirements of our the customer.

Computational chemistry and dtructure-based drug discovery

Different strategies for drug discovery depending on availability of structural data on the protein and its ligand.

Freezing crystals for a synchrotron trip