Low MW Fragment Library

Fragment-based screening methods have emerged in the past decades as an effective way to sample chemical diversity with a limited number of low molecular weight compounds. A key advantage of screening low MW fragments (in comparison with higher MW, HTS-like compounds) is the improved hit rate resulting from screening such small compounds. And many vendors are offering screening libraries for fragment-based drug discovery (FBDD), mainly being guided by the well-known Rule of Three in their design. However, in most of these FBDD-focused libraries, the physicochemical parameters of the fragment-like molecules tend to be closer to their upper limits (MW = 300, ClogP = 3).

Notably, recent tendencies in drug discovery shift towards aiming at leads with lower molecular weight and higher hydrophilicity. It is not surprising, therefore, that even more meticulous criteria must be applied to fragment screening libraries. In particular, lowering the upper molecular weight cut-off value (200 – 240 instead of 300) is strived for by many companies employing the FBDD approach and HTS campaigns in their research.

To meet these principles, Life Chemicals has designed its proprietary Low MW Fragment Library applying several physicochemical filters [1, 2] to its General Fragment Collection. Although the molecular weight is the main parameter which was controlled strictly, other physicochemical characteristics were also well monitored (e.g., more than 80 % of the Library has ClogP < 2). Over 7,200 small-molecule screening compounds that are low-molecular-mass fragments were selected for this Fragment Screening Set.

Parameter MW ClogP TPSA RotB HBD HBA Ring count
Selection range 100 - 225 -3 - 3 0 - 100 Å2 ≤ 3 ≤ 3 ≤ 3 1 - 3
Average value 179.5 0.9 52.1 1.4 1.3 2.4 1.7

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 fragments with low molecular weight

Figure 1. Representative compounds from Low MW Fragment Library

References

  1. Wenlock M. C. et al. J. Med. Chem. 2003, 46, 1250–1256.
  2. Hann M. M. Part of the Series: NATO Science for Peace and Security, Series A: Chemistry and Biology. 2015, 183–196.
  3. Bruns R. F.; Watson I. A. J. Med. Chem. 2012, 55, 9763–9772.
  4. Baell J. B.; Holloway G. A. J. Med. Chem. 2010, 53, 2719–2740.
  5. Thien TV et al. Dokl Biochem Biophys. 2017 Sep;476(1):316-319.
  6. Chen Y et al. Chemosphere. 2018 May;198:226-237.
  7. Lazzarino G et al. Hum Reprod. 2018 Oct 1;33(10):1817-1828.
  8. O'Reilly M. Drug Discov Today. 2019 May;24(5):1081-1086.  
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