Fragment-based drug discovery (FBDD) allows a reduction of the screening library size and coverage of larger unexplored and underrepresented chemical space. It provides more straightforward starting points for subsequent chemical optimization of initial fragment hits.
The process of fragment synthesis obeys a heuristic rule called the Rule of Three. A state-of-the-art tuning of the Rule of Three parameters helps to generate small-molecule compounds with improved ADME profile for efficient lead identification by FBDD and high-throughput screening (HTS).
We have designed the Ultimate Fragment Library by applying the ultimately refined fragment picking approach to the Life Chemicals HTS Compound Collection and General Fragment Library. The Rule of Three and the TPSA ≤ 80 Å2 cut-off. It is known that more than 80 % of drugs on the market have an estimated logSw value greater than -4. Thus, solubility filtering was also used to design this Fragment Screening Subset. Finally, PAINS and in-house developed MedChem filters, such as toxicophore and undesired functionalities, were applied to refine this fragment-like molecule collection, resulting in around 10,300 drug-like fragments. Physicochemical parameters are summarized in the table below:
|Parameter||MW||ClogP||Fsp3||TPSA||RotB||HBD||HBA||Benzene rings||ClogS||Rings||Halogens (except F)||S atoms|
|Selection range||150 - 300||-2 - 3||> 0.4||< 80 Å2||≤ 3||≤ 3||≤ 3||≤ 1||≥ -3||1 - 3||≤ 1||≤ 1|
|Average value||219||1.2||0.5||47||2.2||1.3||2.4||≤ 1||- 1.9||2.2||≤ 1||≤ 1|
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at email@example.com for any additional information and price quotations.
Figure 1. Average values for the main physicochemical parameters for the Ultimate Fragment Library compounds
Figure 2. Representative compounds from Ultimate Fragment Library
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