SMIFH2

**SMIFH2** is a synthetic small molecule inhibitor of the **formin homology 2 (FH2) domain** of formin proteins, which are key actin cytoskeletal regulators. SMIFH2 inhibits formin-mediated actin polymerization by directly targeting the FH2 domain, blocking both nucleation and elongation of actin filaments. It was originally identified through a small molecule screen as an inhibitor of mouse formin mDia1 and demonstrates broad (pan-formin) inhibitory activity across a range of mammalian and non-mammalian formins, with typical IC50 values of 10–20 µM (for human formins) and ~15 µM for mouse Dia1. SMIFH2 does not affect actin polymerization independent of formin nor Arp2/3-complex-mediated assembly. However, subsequent studies have shown that SMIFH2 can also directly inhibit several classes of myosin, notably non-muscle myosin 2A and myosin 5, with some interactions being irreversible at high concentrations. This lack of absolute specificity is likely due to SMIFH2’s electrophilic nature. SMIFH2 is widely used as a research tool in cell biology to dissect formin-dependent processes, including actin cytoskeleton organization, cell migration, and cellular contractility[1][2][3][5][7][10].

Other names

Formin FH2 Domain Inhibitor