Dock5 inhibitor C21 is a specific, direct small molecule inhibitor of guanine nucleotide exchange factor Dock5, inhibits Rac activation by Dock5, efficiently suppresses bone resorption by osteoclasts in vitro and in vivo.
C21 efficiently inhibits the activation of Rac1 by Dock5 DHR2 in HEK293T cells, but has no effect on Rac1 activation by the GEF TrioN.
C21 also affects Dock1 and Dock2 guanine nucleotide exchange factor activity at higher concentrations.
C21 (25 uM) efficiently inhibits the resorption of calcium phosphate matrices and bone resorption, as assessed by measurement of CTX concentration in the culture medium of osteoclasts (OCs).
C21 reversibly disrupts podosome organization in osteoclasts.
C21 systemic injection has no adverse effects in the mouse.
C21 (25 mg/kg/day) protects against ovariectomy-induced bone loss in C57Bl/6J mice.
C21 protects against arthritis- and metastasis-induced bone loss in in mouse models of bovine collagen-induced arthritis (CIA) and osteolytic bone metastasis.
C21 does not affect bone formation.