R992 (MERTK inhibitor) is a novel potent, selective and orally bioavailable inhibitor of Mer tyrosine kinase (MerTK) with IC50 of 18 nM in ADP-Glo assays.
R992 exhibits seven to eight-fold selectivity over AXL and TYRO3 in biochemical assays.
R992 docked in MERTK and the H-bonds R992 forms with three residues in the ATP pocket (MET-647, PRO-672, and ASP-741).
R992 blocks MERTK phosphorylation in HUVEC with EC50 of 32 nM, effectively blocks MERTK phosphorylation in human and murine cells.
R992 (60 mg/kg, orally 2x/day) dose-dependently increases bone nodule formation and increases osteoblast differentiation markers Alpl, SP7, and Runx2.
Treatment with R992 of osteoblasttumor cultures could decrease F-actin content, stress fiber formation, and promoted osteoblast spreading.
R992 inhibits multiple myeloma tumor progression and bone disease in U266 myeloma mouse models.
R992 inhibits tumor progression and cancer-induced bone loss in breast- and lung cancer bone metastasis in the lung- and breast cancer models.