Abstract：
:Cancer remains the most serious disease that threatens human health. Molecularly targeted cancer therapies, specifically small-molecule protein kinase inhibitors, form an important part of cancer therapy. Targeted covalent modification represents a proven approach to drug discovery with the recent FDA approvals of afatanib, ibrutinib, and osimertinib agents, which were designed to undergo an irreversible hetero-Michael addition reaction with a unique cysteine residue of a specific protein. Covalent inhibitors possess numerous advantages, including increased biochemical efficacy, longer duration of action, the high potential for improved therapeutic index due to lower effective dose, and the potential to inhibit certain drug resistance mechanisms. In this regard, the novel targeted anticancer agents whose activity is presumably dependent upon a hetero-Michael addition reaction with thiols are summarized in this article.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Wang L,Zhao J,Yao Y,Wang C,Zhang J,Shu X,Sun X,Li Y,Liu K,Yuan H,Ma Xdoi
10.1016/j.ejmech.2017.09.024subject
Has Abstractpub_date
2017-12-15 00:00:00pages
493-505eissn
0223-5234issn
1768-3254pii
S0223-5234(17)30738-9journal_volume
142pub_type
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