Adhibin is a selective and allosteric inhibitor of RhoGAP class-IX myosins that abrogates ATPase and motor function, suppressing RhoGTPase-mediated modes of cancer cell metastasis.
Adhibin effectively inhibits basal and actin-activated ATPase activity of mammalian and invertebrate Myo9s in the low micromolar range with IC50 values of 2.5 µM and 2.6 µM respectively, but not skeletal muscle myosin (skHMM), β-cardiac muscle myosin-2 (β-cardMyo2), and unconventional class-V myosins, or the three human nonmuscle myosin-2 isoforms (NM2A,−2B,−2C).
Adhibin (0-10 uM) inhibits Myo9 motor function substantially, reducing sliding velocity and motile fraction of actin filaments in a reproducible and reversible manner.
Adhibin suppresses cancer cell migration and adhesion, causes cell detachment, prevents cell spreading, and inhibits migration.
Adhibin interferes with Rho-mediated actin dynamics, actomyosin-based contractility, and cytokinesis.
Adhibin prevents stress fibre formation and interferes with cytokinesis by downregulating RhoA pathways of NM2A/B activation.
Adhibin targets the RhoA signalling cascades regulating the formation, maturation, and maintenance of cell junctions.
Adhibin prevents 3D migration and spheroid formation and retards the growth and proliferation of human colonoids.