Salirasib binds to a cell membrane anchor protein thereby selectively blocking a cascade of biochemical signals known as the Ras signaling pathway. The Ras pathway plays an important role in tumor growth and is believed to be abnormally activated in one-third of human cancers, including cancers of the pancreas, colon, lung and breast. Up to 90% of human pancreatic cancers are driven by aberrant oncogenic Ras signaling.

Ras proteins are cell components that act as on/off switches to regulate enzymatic signaling pathways that control cell proliferation, differentiation, and survival. When attached to the inner cell membrane, Ras becomes biologically active, and then in turn initiates an enzyme sequence (the Ras cascade—Raf, MEK, ERK) that alters cell function (please see slide show). In cancer cells, Ras may be overstimulated by external growth factors, or may exist in mutated form that promotes tumor growth.

Salirasib's unique locus of action provides a mechanism which overcomes the limitations inherent to other Ras-targeted cancer drugs. The mechanism of salirasib action is competitive inhibition of binding of both F-Ras and F-Ras^mut from the galectin binding site, thus preventing activation of the Ras cascades (both the raf and P13K pathways) and mTOR (a tumor stimulator which can operate both through or independent of the P13K pathway).

To get a more visual idea of the Salirasib mechanism of action on the Ras pathway, please see our Salirasib slide show.