Fragment-based drug discovery (FBDD) has become a powerful tool for finding new drugs and has gained widespread application over the past decade. FBDD has become an alternative to traditional lead identification via high-throughput screening (HTS). Unlike HTS, FBDD typically identifies smaller compounds which are called ‘fragments’ that bind to different parts of the biological target. Fragments with low molecular weight are ideal for screening clinical candidates with favorable drug properties, and more and more compounds screened by FBDD are entering into clinical development stage.
In response to this evident trend in drug discovery, BOC Sciences has designed our proprietary Fragment Libraries: Universal Fragment Library, NMR and Crystal Fragment Library, Covalent Library and Featured Fragment Library, including a range of unique fragment subsets.
Figure 1. The Pyramid system allows lead discovery through a fragment-based approach of molecular fragment matching and fitting. (Blundell, T. L.; et al.2006)
Advantages of Fragment Library
- Identified hits have broader chemical space
- Ability to screen a limited number of compounds simultaneously
- Identify novel chemotypes that unexpectedly satisfy the features of the target binding site
- Lead compounds with standard drug similarity parameters
- Save research costs and make it easier to screen for drugs with high performance
Library Design
- List of available chemicals
- Filter according to computed physico-chemical properties: MW, logP, solubility, flexibility
- Molecular weight≤300 Da
- Number of rotatable bonds≤5
- ClogP≤3.5
- Remove compounds with unwanted functionality
The compounds should not contain or result in obviously toxic or reactive templates
- Optionally: select compounds suitable for a particular target class
- Categorize compounds into groups, based on chemical similarity
- Select candidates fragments: medicinal chemistry tractability, availability and cost
- Measure solubility; NMR spectrum; mass spectrum; stability
Our Services
To make it easier and better for researchers, BOC Sciences has designed a Fragment Library containing multiple compound collections. We have prepared the most convenient services for you:
Universal Fragment Library
Based on the fact that fragment-based screening results are largely dependent on the quality of the compound library, BOC Sciences has created our universal fragment-like molecule set which is consist of small molecules that meet the Rule of Three, contains no PAINS. Moreover, our unique library is filtered from toxic/highly reactive compounds by the in-house filters and covers enough chemical space.
NMR and Crystal Fragment Library
FBDD often requires the use of sensitive techniques such as NMR and X-ray crystallography to identify hits in low-molecular-weight fragment compounds with weak binding affinity for the drug target. The hit fragments can then be structurally optimized to form lead compounds with high affinity and specificity. BOC Sciences NMR and Crystal Fragment Library is a product for any level of FBDD project. The library contains several sub-libraries that are consist of a selection of high-quality fragments to meet top industry requirements. It provides an optimal, diverse set of compounds to be included in your next fragment screening.
Covalent Library
The main disadvantage of fragment-based screening is the weak binding affinity of fragment hits, which not only requires sensitive biophysical detection methods, but also makes it difficult and expensive to progress hits to potency. Our Covalent Library addresses these limitations in which covalent binders are easy to detect by mass spectrometry because the primary interaction is well-defined, which simplifies the design of subsequent series, and because the primary hits are already potent.
Featured Fragment Library
The efficient application of bioinformatics and cheminformatics is expected to significantly facilitate the discovery of new drugs due to the exponential increase in the amount of information about a particular target over the past decade. Our well-designed Featured Fragment Library can provide higher hit rate, higher binding efficiency, and multiple starting points for further structure optimization.
Key Features and Benefits
- All fragment compounds are with experimentally assured aqueous solubility in PBS buffer
- Fragments deemed to aggregate as determined by 1H NMR spectra are excluded
- Filtered to exclude reactive substructures and PAINS
Support
- Hit Confirmation: QC check, HPLC repurification, resynthesis
- Hit follow-up: analogs search from stock or REAL Database
- Fast hit exploration libraries synthesis
What We Deliver
- A number of high-quality NMR and Crystal Fragment Libraries different in size and design intention
- Comprehensive support in developing your hit compounds
- All compounds have a minimum purity of 90% assessed by 1H NMR
- Analytical data is available
BOC Sciences provides professional, rapid and high-quality services of Fragment Library design at competitive prices for global customers. Personalized and customized services of Fragment Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Blundell, T. L.; et al. Structural biology and bioinformatics in drug design: opportunities and challenges for target identification and lead discovery. Philosophical Transactions Biological Sciences. 2006. 361(1467): 413-423.
- Fischer, M.; Hubbard, R. E. Fragment-based ligand discovery. Molecular Interventions. 2009. 9(1): 22-30.
- Nikolaj, S.; et al. Library Design Strategies To Accelerate Fragment-Based Drug Discovery. Chemistry A European Journal. 2020. 26(50): 11391-11403.
