FDA-approved small-molecule kinase inhibitors

Peng Wu; Thomas E Nielsen; Mads H Clausen

doi:10.1016/j.tips.2015.04.005

FDA-approved small-molecule kinase inhibitors

Trends Pharmacol Sci. 2015 Jul;36(7):422-39. doi: 10.1016/j.tips.2015.04.005. Epub 2015 May 12.

Authors

Peng Wu¹, Thomas E Nielsen², Mads H Clausen³

Affiliations

¹ Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark. Electronic address: penwu@kemi.dtu.dk.
² Protein and Peptide Chemistry, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
³ Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark; Center for Nanomedicine and Theranostics, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.

PMID: 25975227
DOI: 10.1016/j.tips.2015.04.005

Abstract

Kinases have emerged as one of the most intensively pursued targets in current pharmacological research, especially for cancer, due to their critical roles in cellular signaling. To date, the US FDA has approved 28 small-molecule kinase inhibitors, half of which were approved in the past 3 years. While the clinical data of these approved molecules are widely presented and structure-activity relationship (SAR) has been reported for individual molecules, an updated review that analyzes all approved molecules and summarizes current achievements and trends in the field has yet to be found. Here we present all approved small-molecule kinase inhibitors with an emphasis on binding mechanism and structural features, summarize current challenges, and discuss future directions in this field.

Keywords: cancer; crystal structure; lipid kinase; protein kinase; serine/threonine kinase; tyrosine kinase.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Drug Approval*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Models, Molecular
Molecular Structure
Phosphatidylinositol 3-Kinases / chemistry
Phosphoinositide-3 Kinase Inhibitors
Phosphotransferases / antagonists & inhibitors*
Phosphotransferases / chemistry
Protein Binding
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / chemistry
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / chemistry
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
Receptor Protein-Tyrosine Kinases / chemistry
United States
United States Food and Drug Administration

Substances

Enzyme Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors
Phosphotransferases
Protein-Tyrosine Kinases
Receptor Protein-Tyrosine Kinases
Protein Serine-Threonine Kinases