Fragment-based · ~3,200 compounds
FBL – Fragment-Based Library
About 3,200 small, structurally diverse fragments (FBL-3200) with low molecular weight and high solubility, assembled for fragment-based drug discovery.
Fragment-based drug discovery looks for highly diverse, rather small ligands that can increase binding efficiency and bioavailability once joined in a new molecule. FBDD is also a great complement to any HTS campaign for enzyme targets: it aids early hit discovery and optimization when data from both screening approaches are compared. A fragment-library screen is target-specific in fit, being comprised of minimum pharmacophores. FBDD “combines the empiricism of random screening with the rationality of structure-based design.” If available, any structural-parts match between HTS and FBDD hits is a good foundation for preliminary SAR.
TimTec Fragment-Based Library, FBL, gathers structurally diverse ligands with low molecular weight and high solubility. The set of about 3,200 fragments (FBL-3200) is intended for customized subset selection; some techniques, especially those that use fragment mixtures, can approach the full collection. Design criteria sit mid-way to accommodate structural diversity and versatility, including and going beyond Rule-of-3 restrictions, with larger fragments of up to three rings.
FBL design criteria
| Parameter | Range |
|---|---|
| MW | 110–290 |
| ClogP | ≤ 2.5 |
| HBA | ≤ 5 |
| HBD | ≤ 3 |
| Rotatable bonds | ≤ 5 |
| Heavy atoms (non-hydrogen) | ≤ 20 |
| Rings | 0–3 |
| Polar surface area | Not defined |
| LogS (calculated) | >10−3 |
| Concentration | 1.5 mM |
| Potential Ki/Kd | ~0.1–1.0 mM |
Calculations are performed using TimTec proprietary software ChemDBsoft. Compounds can be delivered in dry form in custom milligram or micromolar amounts, or as freshly prepared DMSO solution aliquots.
Published screens that used FBL
These are literature reports, not TimTec efficacy claims:
- Meiby, E.; Knapp, S.; et al. Fragment screening of cyclin G-associated kinase by weak affinity chromatography. Anal. Bioanal. Chem. 2012, 404(8), 2417–2425. doi:10.1007/s00216-012-6335-6. TimTec FBL (3,200 fragments) used for GAK / WAC–MS; ST088036 among the highest-ranked hits.
- Duong-Thi, M.-D.; Bergström, M.; et al. High-throughput fragment screening by affinity LC-MS. J. Biomol. Screen. 2013, 18(2), 160–171. doi:10.1177/1087057112459271. TimTec FBL subset; selective hit ST036785 at human α-thrombin.
- Duong-Thi, M.-D.; Bergström, M.; et al. Weak affinity chromatography for evaluation of stereoisomers in early drug discovery. J. Biomol. Screen. 2013. doi:10.1177/1087057113480391. Follow-on WAC stereoisomer work from the same FBL series.
Ask for the current SDF and subset files before designing a campaign; membership can change as lots are retired or replaced.