PLX647 (C09-1164-157)

PLX647 is an orally active, highly specific dual FMS and KIT kinase inhibitor, with IC 50 s of 28 and 16 nM, respectively. PLX647 shows selectivity for FMS and KIT over a panel of 400 kinases at a concentration of 1 μM except FLT3 and KDR (IC 50 s=91 and 130 nM, respectively).In VitroIn vitro, PLX647 potently inhibits proliferation of BCR-FMS cells, with an IC 50 of 92 nM. A corresponding Ba/F3 cell line expressing BCR-KIT is also quite sensitive to PLX647, with an IC 50 of 180 nM. PLX647 also inhibits endogenous FMS and KIT, as demonstrated by inhibition of the ligand-dependent cell lines M-NFS-60 (IC 50 =380 nM) and M-07e (IC 50 =230 nM), which express FMS and KIT, respectively. PLX647 potently inhibits the growth of FLT3–ITD-expressing MV4-11 cells (IC 50 =110 nM). PLX647 displayed minimal inhibition of the proliferation of Ba/F3 cells expressing BCR–KDR (IC 50 =5 μM). PLX647 inhibits osteoclast differentiation with an IC 50 of 0.17 μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoPLX647 (40 mg/kg; p.o.; twice daily for 7 days) reduces macrophage accumulation in UUO kidney and blood monocytes . PLX647 (40 mg/kg; p.o.; male Swiss Webster mice) reduces LPS-induced TNF-α and IL-6 release . PLX647 (20-80 mg/kg; p.o.; daily or twice daily from 27-41 days) shows effects on collagen-induced arthritis . PLX647 (30 mg/kg) results in significant inhibition of TRAP5b immunostaining and bone osteolysis. PLX647 (30 mg/kg BID) is able to prevent bone damage by the tumor cells . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57BL/6 mice (mouse unilateral ureter obstruction model) Dosage: 40 mg/kg Administration: P.o.; twice daily for 7 days Result: Resulted in reduction in the levels of F4/80+ macrophages by 77%. Animal Model: 7-9 wk old Male DBA/1J mice (Mouse collagen-induced arthritis model) Dosage: 20 mg/kg, 80 mg/kg Administration: P.o.; daily (20 mg/kg) from 27-41 days, twice daily (80 mg/kg) from 27-41 days Result: 20 mg/kg PLX647 had no initial effect on the development of severe arthritis. However, starting on day 33, no further development of disease severity was recorded, and a 30% inhibition of the macroscopic signs of arthritis was evident in clinical score on day 41. Mice treated with 80 mg/kg BID PLX647 initially shows delayed development of severe arthritic signs. Starting on day 33, the signs of arthritis began to decrease in this treatment group, reaching a maximum reversal of 76% on day 41.Form:Solid. Specification: 0.99 Molecular Formula: C21H17F3N4 Molecular Weight: 382.38 EC Number: 809-725-4 PubChem CID: 11545419 Isomeric SMILES: C1=CC2=C(NC=C2CC3=CN=C(C=C3)NCC4=CC=C(C=C4)C(F)(F)F)N=C1