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Ultimate Fragment Library

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 orders@lifechemicals.com for any additional information and price quotations.

 Figure 1. Average values for the main physicochemical parameters for the Ultimate Fragment Library compounds

 Ultimate Fragment Library  representative compounds

Figure 2. Representative compounds from Ultimate Fragment Library

 

References

  1. Erlanson, D. A.; McDowell, R. S.; O’Brien, T. Fragment-based drug discovery. J. Med. Chem. 2004, 47, 3463–3482.
  2. Rees, D. C.; Congreve, M.; Murray, C. W.; Carr, R. Fragment-based lead discovery. Nat. Rev. Drug Discovery 2004, 3, 660–672.
  3. Bian Y1,2,3, Xie XS4,5,6,7,8. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications // AAPS J. 2018 Apr 9;20(3):59. doi: 10.1208/s12248-018-0216-7.
  4. Price AJ1, Howard S1, Cons BD2. Fragment-based drug discovery and its application to challenging drug targets // Essays Biochem. 2017 Nov 8;61(5):475-484. doi: 10.1042/EBC20170029.
  5. Mello JDFRE1, Gomes RA1, Vital-Fujii DG1, Ferreira GM1,2, Trossini GHG1,2. Fragment-based drug discovery as alternative strategy to the drug development for neglected diseases // Chem Biol Drug Des. 2017 Dec;90(6):1067-1078. doi: 10.1111/cbdd.13030.
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