Abstract:
:Inhibition of Ras signalling has been a goal almost since its central role in cell signalling and its deregulation in disease were discovered. Early attempts at inhibiting its post-translational modification using peptidomimetics were successful in cell culture but failed spectacularly in clinical trials, making industry wary of targeting this critical oncoprotein. Small molecule inhibition of the protein-protein interactions involving Ras has also been difficult due to the nature of the interaction interface. Recent improvements in design, synthesis and selection of stabilised peptides, peptidomimetics and macrocycles have suggested that these biologics may represent a new hope in Ras inhibition. Here we review the various ways in which Ras has been targeted with these molecules. We also describe work on related small G proteins of the Ras superfamily, since many of the principles may be applicable to Ras, and these also provide inhibition of pathways downstream of Ras.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Mott HR,Owen Ddoi
10.1016/j.semcancer.2018.01.001subject
Has Abstractpub_date
2019-02-01 00:00:00pages
149-161eissn
1044-579Xissn
1096-3650pii
S1044-579X(17)30281-Xjournal_volume
54pub_type
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