Because prenylation is important for RAS membrane localizati...

created [InstanceEdit:9653499] Rothfels, Karen, 2019-07-11
dbId 9653498
displayName Because prenylation is important for RAS membrane localizati...
modified [InstanceEdit:9731761] Stephan, Ralf, 2021-05-24
schemaClass Summation
text Because prenylation is important for RAS membrane localization and function, inhibition of this step of RAS processing was viewed as a promising early therapeutic target for RAS-driven cancers (reviewed in Gysin et al, 2011). Farnesyltransferase inhibitors such as lonafarnib and tipifarnib are small molecule CaaX competitive inhibitors that inhibit cell growth of a range of cancer cell lines and tumor xenografts (Njoroge et al, 1998; End et al, 2001; Liu et al, 1998; Ashar et al, 2001). Unfortunately, the clinical use of these drugs is hampered by the fact that both KRAS and NRAS can be geranylgeranylated when FTase is inhibited, restoring membrane localization and function (Fiordalisi et al, 2003). FTase inhibitors may have clinical use in the treatment of HRAS driven cancers, such as bladder and thyroid cancers (reviewed in Gysin et al, 2011; Lu et al, 2016).

Lonafarnib is a farnesyltransferase inhibitor of growth factor signalling that prevented SARS-CoV-2 replication in Caco-2 and UKF-RC-2 cells at clinically achievable concentrations (Klann et al, 2020).
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