Revere Pharmaceuticals | Rac1 GTPase

The critical role of Rac1 in cancer

Rac1 and its variants are proteins that function as central signaling nodes for diverse pathways that drive various cancer promoting processes including cell growth, migration, invasion, and angiogenesis. These proteins switch between the inactive guanosine diphosphate (or GDP-bound form) and the active guanosine triphosphate (or GTP-bound form). The active GTP form recruits downstream effector proteins to activate oncogenic pathways.

While GTPases in general have been elusive drug discovery targets, our proprietary methods have enabled us to discover promising inhibitors for these signaling proteins. We have developed an industry-leading suite of biochemical and cell-based assays designed for conducting research on Rho GTPases. These assays, together with computer-aided drug design, provide the foundation for a sustainable pipeline of first-in-class drugs to address unmet needs for cancer patients.

Rac1: a critical but unexploited cancer target

Aberrant Rac1 signaling promotes cancer cell growth, migration, invasion, and tumor angiogenesis. Overexpression and activation of Rac1 correlate with inferior prognosis in multiple cancers and are associated with resistance to chemotherapy and other therapeutics.

Revere’s drug discovery efforts address cancers with overexpressed wild type Rac1, the Rac1b oncogenic splice variant, and the Rac1 P29S mutant to address cancers characterized by these aberrations. Companion diagnostics for the Rac1b and P29S programs are being developed which will enable precision oncology patient selection strategies.

Xenograft data reveals excellent in vivo single agent activity of Revere compound 32661. The combination of our compound with a standard-of-care HER2 targeted agent shows prolonged tumor growth inhibition with no toxicity.

Our novel Rac1 inhibitors show significant anti-tumor activity as single agents and in combination with standards of care in animal models of colorectal, breast, prostate, kidney, melanoma, ovarian cancers.

Targeting Rac1 GTPases: “molecular switches” that drive cancer progression

The critical role of Rac1 in cancer

Rac1: a critical but unexploited cancer target

Rac1 GTPase activation and signaling in cancer

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