The ADMET-like Fragment Library is a specialized collection of over 17,600 fragment-like small molecules, designed to support rapid identification of high-quality fragment hits with favorable pharmacokinetic and toxicological profiles for downstream lead optimization.
This fragment-focused screening Set enables early drug discovery projects to balance chemical tractability, target engagement, and developability from the very outset. It covers low-molecular-weight fragments with high structural diversity, combined with the simplicity and flexibility required for chemical elaboration through fragment-growing, linking, and merging strategies to achieve high-affinity binding to protein targets while minimizing attrition risks associated with poor solubility, permeability, or metabolic instability.
The Screening Set distinguishing characteristics:
- Optimized for fragment-based drug discovery (FBDD)
- Designed with ADMET-property awareness to reduce downstream optimization risk
- High structural diversity with excellent chemical tractability
- Compatibility with biophysical screening, X-ray crystallography, NMR and SPR
- Seamlessly complementing our broader ADMET-like Screening Compound Library
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Representative screening compounds from the Screening Library
Fragment Design and ADMET-Driven Filtering
Our ADMET-like Fragment Library comprises over 17,600 low-molecular-weight fragments, selected from the proprietary General Fragment Library using stringent fragment-specific criteria aligned with industry best practices for FBDD and Rule of Three (Ro3) compliance:
- Molecular weight < 300 Da
- Lipophilicity (cLogP < 3)
- Hydrogen bond donors ≤ 3
- Hydrogen bond acceptors ≤ 3
- Rotatable bonds ≤ 3
These parameters are specifically chosen to enhance aqueous solubility, ligand efficiency, cell permeability, and metabolic stability, while preserving sufficient chemical space for medicinadmetal chemistry expansion.
Value in Modern Drug Discovery
ADMET-like fragments are particularly valuable for challenging and novel biological targets, including proteins with shallow, flexible, or poorly defined binding pockets. By starting with fragments with optimized physicochemical and pharmacokinetic profiles, discovery teams can reduce off-target liabilities and increase the probability of success during hit-to-lead and lead-optimization stages.
The Library is well-suited for drug discovery programs across multiple therapeutic areas, including oncology, infectious diseases, and neurodegenerative disorders, where fragment-based approaches have repeatedly demonstrated their ability to generate high-quality clinical candidates through iterative structure-guided optimization [1, 2].
Figure 1. Timeline highlighting key papers influencing the course of FBDD (blue) and important dates showing its success (orange). In an early conceptual paper, Jencks outlined the additivity of binding energies for fragments of larger molecules (picture adapted from Bon, M. et al., 2022 [3]).
Reference:
- Erlanson, D. A., et al. (2016). Twenty years on: the impact of fragments on drug discovery. Nature Reviews Drug Discovery, 15(9), 605–619.https://doi.org/10.1038/nrd.2016.109
- Shuker, S. B., et al. (1996). Discovering high-affinity ligands for proteins: SAR by NMR. Science, 274(5292), 1531–1534.https://doi.org/10.1126/science.274.5292.1531
- Bon, M., Bilsland, A., Bower, J. and McAulay, K. (2022), Fragment-based drug discovery—the importance of high-quality molecule libraries. Mol Oncol, 16: 3761-3777.https://doi.org/10.1002/1878-0261.13277