Fragment-based Drug Design

Fragment-based drug discovery (FBDD) has become one of the most prominent strategies used to identify innovative drug discoveries. The selection of advantageous fragment combinations or extensions to create novel drug molecules, producing highly active therapeutic candidates, forms the theoretical foundation of FBDD. FBDD strategies have led to many successful drug discoveries.

Our company has extensive research in the area of FBDD capabilities. Our FBDD services are designed to increase the success rate and speed of delivery of your project.

Service Overview

While high-throughput screening (HTS) aims to identify drugs with medium to high affinity for typical drug molecules of comparable size, FBDD looks for small molecules with weaker but more refined affinity for their biological targets. The goal of FBDD is to cultivate and create pharmaceuticals, not to search for analogs of already-known molecules.

To quickly find and characterize fragment hits, our company has developed an FBDD platform that combines proprietary fragment collection with high-throughput biophysical screening technologies. In order to enable fragment growth into lead compounds, our FBDD platform is further improved with X-ray crystallography, computationally guided high-throughput chemistry, and orthogonal screening methods.

Services Contents

• High-throughput screening and active compound discovery based on structure design.
• Discovery of active compounds to lead compounds.
• Optimization of lead compounds to identify preclinical drug candidates.
• Structure-activity relationship studies.
• Feasibility assessment of new drug targets.

Service Advantages

• Short and fast calculation cycle time.
• High calculation accuracy.
• Computer-aided drug design saves a lot of labor costs.
• Far less capital is required than for biological or chemical experiments.

Research Capabilities

The first step in the FBDD approach is to build a rational fragment library using the relevant principles of HTS. Our novel fragment library has been carefully designed to be easily optimized for medicinal chemistry. Our prepared fragments contain at least one diversity point for further derivatization, and in addition, the library contains a small number of analogs around each functional group to allow rapid evaluation of any conformational relationships around each core fragment.

Features of the FBDD fragment library

• Fragments have a small molecular weight, a low number of hydrogen bond donors and acceptors, and weak binding to the target.
• Fragments have good solubility for use in highly concentrated solutions.
• Fragment molecules conform to the "three rules" - molecular weight less than 300, hydrogen bond donors and acceptors no more than 3, rotatable bonds no more than 3, cLogP less than 3.
• Screening and identification of active fragments that bind weakly to the target protein.

Fig.1 A flowchart of FBDD. (Li X, et al. 2020)

Our company's FBDD platform provides access to the following.

• Orthogonal Screening Techniques: Techniques include thermal shift analysis, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), NMR, high-concentration biochemical analysis and X-ray crystallography
• Structural Biology: Experience in developing structural routes to support FBDD.
• Computational chemistry: Proprietary fragment hit extension techniques and fragment shape-based analysis tools
• Medicinal Chemistry: Expertise in structure-based drug discovery and fragment hit optimization.

If you are looking for smarter, higher quality solutions that incorporate best practices, please feel free to contact us.

Reference

1. Li X, et al. (2020). "Application of Fragment-Based Drug Discovery to Versatile Targets." Front Mol Biosci. 7: 180.

It should be noted that our service is only used for research, not for clinical use.