2-Benzofurancarboxamide, N-[3-chloro-4-[4-(2-methyl-1-oxopropyl)-1-piperazinyl]phenyl]-

Description

Rasarfin (674359-73-0) is a dual inhibitor of Ras and ARF6 discovered by screening a library of over 115,000 small molecules employing an endosomal BRET-based assay with the prototypical GPCR angiotensin II type 1 receptor (AT1R) seeking to identify inhibitors of receptor trafficking. IC50=7 and 0.7 μM for ARF and Ras respectively with no inhibition of Rac/Cdc42 and Rho up to 100 μM. It blocks agonist-mediated internalization of AT1R and other GPCRs. It also potently inhibits agonist-induced ERK1/2 signaling by GPCRs and MAPK and AKT signaling by EGFR (IC50=4-5 μM) and prevents cancer cell proliferation. Rasarfin’s direct action on Ras was also verified using purified H-Ras in an in vitro GEF exchange assay.1

References

Giubilaro et al. (2021), Discovery of a dual Ras and ARF6 inhibitor from a GPCR endocytosis screen; Nat. Commun. 12 4688