Fragment-based drug discovery (FBDD) projects performed with 19F NMR-assisted screening are becoming an essential and widespread method in drug discovery. Fluorine yields a strong, sharp, and distinct signal in NMR spectra. It has a wide chemical shift range and is highly sensitive to the immediate molecular environment. These factors enable an efficient application of this method even in laboratories with limited NMR capabilities.
Pooling and combining (“cocktailing”) fluorinated fragments in fragment-based screening through 19F NMR allows simultaneous screening of multiple compounds without interference, offering a high-throughput approach to identify initial hits efficiently and enabling a more streamlined and effective drug discovery process. It's an efficient way to explore a broader chemical space and identify initial starting points for subsequent drug development. The process of determining the best fragment-fit post-NMR involves analyzing the spectral changes in the presence of the protein and comparing them to the spectra of individual fragments. This comparison helps in identifying which fragments have interacted most strongly or favorably with the target protein, providing valuable insights for subsequent lead optimization.
Our expert team has designed this unique Fluorine Fragment Cocktail Library by pooling sets of 10 fragment-like screening compounds with the most dissimilar 19F chemical shifts to facilitate the interpretation of screening results. Several physicochemical parameters and medicinal chemistry structure filters were employed to guarantee the drug-likeness of the selected molecules. A careful selection of fluorinated fragments was performed to ensure structural diversity with broad coverage of chemical space, varied local environment of fluorine in the structure, as well as experimentally confirmed solubility both in DMSO and phosphate-buffered saline.
The resulting Screening Set contains 173 Fluorine Fragment Cocktails comprising 1,730 in-stock drug-like fluorine-containing fragments from our proprietary Fluorine Fragment Library that satisfy the following parameters:
- Single-type fluorine group
- Only 1 peak in the 19F NMR spectrum per compound in the majority of cases
- No reactive and unstable compounds
- DMSO soluble at 200 mM
- PBS soluble at ≥ 0.1 mM
- Purity > 90 %
Overall physicochemical parameters of the Library:
- 130 < MW < 300
- -2.6 < ClogP < 3.9
- H-bond Donors ≤ 4
- H-bond Acceptors ≤ 5
- Rotatable bonds ≤ 10
- TPSA ≤ 120 Å2
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.
Example of the fluorine-containing fragments from the Fluorine Fragment Cocktails
Cocktail #2
Cocktail #85
Cocktail #160
References
- Nagatoishi S, Yamaguchi S et al. Bioorg Med Chem. 2018 May 1; 26(8):1929-1938.
- Norton, R.; Leung, E.; Chandrashekaran, I.; MacRaild, C. Molecules 2016, 21 (7), 860.
- Nosik, P. S., Gerasov, A. O. et al. Adv. Synth. Catal. 359 (2017), 3126-3136
- Gerasov, A., Dolgonos, G. A. et al. Synthesis (Stuttg). Published online: 2020 Jan.