Fragment-based screening (FBS) is a widely utilized strategy for the discovery of lead compounds. Especially in the development of drugs against unconventional targets such as protein-protein interactions (PPIs), FBS has proven to be a viable alternative to high-throughput screening (HTS). Leveraging advanced fragment-based drug design (FBDD) platform, Creative Biostructure provides FBS solutions for customers with hit identification needs, which involve various biophysical methods to determine the exact binding fragments.
Figure 1. Comparison of HTS and fragment-based screening.
|Library Capacity||Library typically <5,000||Library typically >100,000|
|Molecular Weight||Molecular weight <300Da||Molecular weight >300Da|
|Coverage||A much greater chemical space can be efficiently probed||Coverage of chemical space can be poor|
|Target Specificity||Well-characterized targets||A broader range of targets including whole-well screening approaches|
|Ability||Iterative step-by-step optimization possible to increase the size and potency of the molecule||Can be difficult to optimize hits as the structures can be complex|
|Throughput||Low-medium throughput||High throughput|
Therefore, FBS enables a larger chemical structure space to be more effectively probed with fewer compounds and hit rates for FBS appear to be higher (3-10%). At Creative Biostructure, we support the use of many biophysical techniques to measure the weak and medium affinity of fragments. These biophysical techniques can provide insight into the binding mode of fragments, allowing fragment hits to be developed into lead-like compounds in a structure-guided approach. We recommend using two different screening techniques and then focusing on the fragments that are active in both assays.
Creative Biostructure is committed to providing customers with cost-effective, high-quality solutions for hit identification. Our team has a deep understanding of FBS-related biophysical screening techniques and can propose appropriate experimental protocols according to the specific projects of customers, professionally explain the screening results, and assist in downstream optimization.