General Fragment Library

Fragment-based lead discovery (FBLD) is an efficient modern approach to drug discovery. It is based on screening relatively small fragment libraries (typically, a few thousand compounds) and identification of potential hits that may bind only weakly to the biological target (millimolar affinities can be considered significant enough). The reduced size and complexity of those molecules allow more efficient chemical space sampling. The subsequent growing and/or combining of the fragments leaves more opportunities to produce a lead with a higher affinity and improved physicochemical properties [1-5].

The Life Chemicals General Fragment Library comprises about 49,000 fragments with MW ≤ 300 and ClogP ≤ 3.0, readily available for fragment-based drug discovery projects.

More scrupulous assay applying expanded Rule of Three parameters and additional physicochemical and structural filters enabled us to propose the Advanced Subset of over 16,700 in-stock fragments. The criteria used to design The Life Chemicals Advanced Fragment Subset are listed in the table below. Additionally, the compounds were evaluated by Substructure and PAINS structural filters [6-7].

Cherry-picking is available. Please, contact us at orders@lifechemicals.com for any details and quotations.

Parameter

Range

Average Values

MW

100 - 300

225

ClogP

-2 - 3

1.1

TPSA

 < 100 Å2

54.5 Å2

Rotatable bonds

≤ 3

2.2

H-donors

≤ 3

1.2

H-acceptors

≤ 4

2.6

logS

≥ - 3.5

-2.2

Rings count

1 - 4

2.4

-CN, -NO₂, - Br count

≤ 1

≤ 1

-S, -Cl count

≤ 2

≤ 2

Benzene ring count

≤ 1

≤ 1

 

General Fragment Library representative compounds

Figure 1. Representative fragment molecules from General Fragment Library 

References

  1. Erlanson D. A.; McDowell R. S.; O’Brien T. J. Med. Chem. 2004, 47, 3463-3482
  2. Rees D. C.; Congreve M.; Murray C. W.; Carr R. Nat. Rev. Drug Discovery 2004, 3, 660-672.
  3. Ohlson S1, Duong-Thi MD2. Fragment screening for drug leads by weak affinity chromatography (WAC-MS) // Methods. 2018 Aug 15;146:26-38. doi: 10.1016/j.ymeth.2018.01.011.
  4. Ray PC, Kiczun M, Huggett M, Lim A, Prati F, Gilbert IH, Wyatt PG. Fragment library design, synthesis and expansion: nurturing a synthesis and training platform // Drug Discov Today. 2017 Jan;22(1):43-56. doi: 10.1016/j.drudis.2016.10.005.
  5. Williams G1, Ferenczy GG2, Ulander J3, Keserű GM4. Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery // Drug Discov Today. 2017 Apr;22(4):681-689. doi: 10.1016/j.drudis.2016.11.019.
  6. Bruns R. F.; Watson I. A. Rules for identifying potentially reactive or promiscuous compounds. J. Med. Chem. 2012, 55, 9763–9772.
  7. Baell J. B.; Holloway G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays.J. Med. Chem. 2010, 53, 2719–2740.
This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. By using our website, you accept our conditions of use of cookies to track data and create content (including advertising) based on your interest. Accept