PLX647 dihydrochloride is a potent and selective dual inhibitor of FMS and KIT kinases, with IC50 values of 28 nM and 16 nM, respectively. At a concentration of 1 μM, PLX647 dihydrochloride demonstrates superior selectivity against a wide range of 400 kinases, except FLT3 and KDR, where IC50 values are 91 nM and 130 nM, respectively. This orally active compound holds great potential for targeted kinase inhibition.

In vitro, PLX647 dihydrochloride demonstrates significant inhibitory effects on the proliferation of various cells. It potently halts the growth of BCR-FMS cells with an IC 50 of 92 nM, and shows similar potency towards a Ba/F3 cell line expressing BCR-KIT, presenting an IC 50 of 180 nM. This compound also effectively suppresses endogenous FMS and KIT signaling, indicated by its ability to inhibit M-NFS-60 and M-07e cell lines, which express FMS and KIT, respectively, with IC 50 values of 380 nM and 230 nM. Additionally, PLX647 dihydrochloride significantly inhibits FLT3-ITD-expressing MV4-11 cells with an IC 50 of 110 nM, but it exerts minimal inhibition on the proliferation of Ba/F3 cells expressing BCR-KDR, with an IC 50 of 5 μM. Moreover, this compound inhibits osteoclast differentiation, marked by an IC 50 of 0.17 μM.

PLX647 dihydrochloride administered at 40 mg/kg orally, twice daily for 7 days, significantly reduces macrophage accumulation in unilateral ureter obstruction (UUO) kidney and blood monocytes, as well as decreasing LPS-induced TNF-α and IL-6 release in male Swiss Webster mice. Further, dosages ranging from 20-80 mg/kg administered orally daily or twice daily from days 27 to 41 demonstrate efficacy in collagen-induced arthritis models in mice, with 20 mg/kg showing no initial effect but eventually inhibiting the macroscopic signs of arthritis by 30% on day 41, while 80 mg/kg results in a 76% reversal of disease severity by the same day. At a 30 mg/kg dosage, PLX647 dihydrochloride notably inhibits TRAP5b immunostaining and bone osteolysis, and effectively prevents bone damage caused by tumor cells. In a mouse unilateral ureter obstruction model using male C57BL/6 mice, the administration resulted in a 77% reduction in F4/80+ macrophages after 7 days. In a mouse collagen-induced arthritis model with 7-9 week old male DBA/1J mice, the compound at 20 mg/kg showed no initial therapeutic effect, but from day 33, halted further development of severe arthritis, whereas at 80 mg/kg, it delayed the onset and significantly reduced arthritic signs from day 33, achieving a noteworthy reversal by day 41.