Abstract：
:The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct inhibitors of KRAS. Thus, this article provides an overview of the history and recent progress in the development of pharmacological strategies to target oncogenic KRAS with small molecule agents. Mechanistically, these KRAS-targeted agents can be classified into the following four categories. (1) Small-molecule RAS-binding ligands that prevent RAS activation by binding within or outside the nucleotide-binding motif. (2) Inhibitors of KRAS membrane anchorage. (3) Inhibitors that bind to RAS-binding domains of RAS-effector proteins. (4) Inhibitors of KRAS expression. The advantage and limitation of each type of these anti-KRAS agents are discussed.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Chuang HC,Huang PH,Kulp SK,Chen CSdoi
10.1016/j.phrs.2017.01.006subject
Has Abstractpub_date
2017-03-01 00:00:00pages
370-376eissn
1043-6618issn
1096-1186pii
S1043-6618(17)30017-8journal_volume
117pub_type
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