Recent development of cyclic amide (pyridone/lactam) moiety containing heterocycles as protein kinase inhibitors

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


Staurosporine, pyridone 6 and hydroxyfasudil are cyclic amide (pyridone/lactam) moiety containing heterocycles that are discovered/developed as potent protein kinase inhibitors targeting on the ATP (Adenosine-5'- triphosphate) binding pocket. Despite different molecular shapes (pentacycle, tetracycle and bicycle, respectively), they all bind to the residues of the hinge region at ATP binding pocket of protein kinases in a very similar manner: the cyclic amide moiety occupies the adenine region of ATP binding pocket and forms at least two hydrogen bonding interaction with the hinge region via its hydrogen bond acceptor/donor pair. Using a few examples of cyclic amide (pyridone/lactam) moiety containing heterocyclic protein kinase inhibitors, this review discusses their therapeutic application, structural basis of kinase inhibition, as well as their associated syntheses. It is anticipated that the design, synthesis and profiling of the kinasebiased library based upon the cyclic amide (pyridone/lactam) moiety containing core scaffolds may significantly enhance the efficiency of high-throughput screenings (HTS), accelerate hit-to-lead process and improve the success rate in the development of protein kinase inhibitors for the treatment of various diseases especially cancer.

Original languageEnglish (US)
Pages (from-to)234-253
Number of pages20
JournalCurrent Medicinal Chemistry
Issue number3
StatePublished - 2010
Externally publishedYes


  • Cancer
  • Cyclic amide (pyridone/lactam)
  • High-throughput screenings
  • Hydroxyfasudil
  • Kinase-biased library
  • Protein kinase inhibitor
  • Pyridone 6
  • Staurosporine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


Dive into the research topics of 'Recent development of cyclic amide (pyridone/lactam) moiety containing heterocycles as protein kinase inhibitors'. Together they form a unique fingerprint.

Cite this