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New opportunities for covalent drugs published by Avila scientists
Date:4/1/2011

description of progress in the design of targeted covalent drugs with a focus on the Avila strategy is discussed.

  • Several rationally designed, targeted covalent inhibitors have recently advanced in clinical development (neratinib, afatinib, PCI-32765 and the Avlia clinical candidate, AVL-292).

  • New publications have reported on targeted covalent inhibitors to diverse drug targets where each demonstrates high specificity of covalent bond formation to its respective target.

  • The pharmacological advantages of covalent drugs are discussed including the potential to address the problem of drug-resistance mutations that often arise in cancer and in infectious diseases.

    Based on this review article, it is apparent that structural bioinformatics approaches, coupled with structure-based drug design, may enable the engineering of highly selective covalent drugs and a resurgence of interest in this important class of therapeutics.


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