Adhibin

Adhibin is a selective allosteric inhibitor of RhoGAP class-IX myosins (Myo9a/b), with IC50 values of ~2.5 µM, disrupting ATPase and motor functions critical for RhoA/ROCK-mediated actin dynamics and contractility. It suppresses cancer cell adhesion, migration, and invasion in vitro, without significant toxicity up to 25 µM, and shows no systemic toxicity in vivo at doses up to 0.142 mg/kg (i.p.) in mice. Mechanistically, adhibin perturbs actomyosin structures, reduces active RhoA levels by up to 95%, and prevents focal adhesion formation, uniquely targeting metastasis-related processes. Additionally, adhibin induces cell rounding and detachment, delays cell cycle progression, and is effective in both single and collective migration contexts.