General Covalent Inhibitor Library

Life Chemicals presents the General Covalent Inhibitor Library of over 17,800 small-molecule screening compounds for covalent screening selected from the Life Chemicals HTS Compound Collection by specific structural moieties (functional groups), sometimes referred to as “warheads”, that are known to form covalent bonds with amino acid residues (e.g., Cys, Ser, Lys, Tyr) in binding sites of target proteins.

The following chemical classes and structural features were used for selection of possible covalent binding irreversible inhibitors:

  • β-lactams
  • Alkyl halides
  • Epoxides, aziridines
  • Michael acceptors:
    • α,β-unsaturated ketones,  -nitriles, -esters;
    • maleimide-like compounds;
    • activated vinyl derivatives
  • Cyanoacrylamides
  • Sulfonate esters
  • Sulfonyl fluorides

 

  • Rodanides
  • Thiourea and thioketones
  • o-quinones
  • p-quinones
  • Ketales
  • Acetales
  • Disulfides
  • Terminal acetylenes
  • Sulfoalkenes
  • Aromatic nitriles
  • Phenol benzoate derivatives

You can cherry-pick compounds or focus on a specific class of covalent modifiers. Separate focused sets of covalent binders targeting each of the indicated amino acid residues (Cysteine, Serine, Lysine, Tyrosine) can be provided on request. Please, contact us at orders@lifechemicals.com for any details and quotations.

The average values of the key physicochemical parameters in the General Covalent Inhibitor Library.

Figure 1. The average values of the key physicochemical parameters in the General Covalent Inhibitor Library.

References:

  1. K. Zhu, K. W. Borrelli, J. Greenwood, T. Day, R. Abel, R. Farid, E. Harder J. Chem. Inf. Model., June 2014. doi: 10.1021/ci500118s
  2. D. T. Warshaviak, G. Golan, K. W. Borrelli, K. Zhu, O. Kalid J. Chem. Inf. Model., March 2014. doi: 10.1021/ci500175r
  3. Q. Liu, Y. Sabnis, Z. Zhao, T. Zhang, S. J. Buhrlage, L. H. Jones, N. S. Gray Cell Press: Chem. Biol., Vol. 20 (2), 2013, pp. 146–159.
  4. R. Mah, J. R. Thomas, C. M. Shafer Bioorg. Med. Chem. Lett., Vol. 24, 2014, pp. 33–39.
  5. D. S. Johnson, E. Weerapana, B. F. Cravatt Future Med. Chem., Vol. 2 (6), 2010, pp. 949–964.
  6. E. Weerapana, G. M. Simon, B. F. Cravatt Nature Chemical Bioogyl., Vol. 4, 2008, pp. 405–407.
  7. S. G. Kathman, Z. Xu, A. V. Statsyuk J. Med Chem., Vol. 57 (11), 2014, pp. 4969–4974.
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