PLX647 dihydrochloride 是一种具有口服活性的，具有高度特异性的FMS和KIT双激酶抑制剂，IC50分别为 28 和 16 nM。PLX647 dihydrochloride (1 μM) 在 400 个激酶组中显示出对 FMS 和 KIT 有选择性，但 FLT3 和 KDR 除外 (IC50= 91 和 130 nM)。
| 生物活性 | PLX647 dihydrochloride is an orally active, highly specific dualFMSandKITkinase inhibitor, withIC50s of 28 and 16 nM, reapectively. PLX647 dihydrochloride shows selectivity for FMS and KIT over a panel of 400 kinases at a concentration of 1 μM exceptFLT3and KDR (IC50s=91 and 130 nM, respectively)[1]. |
体外研究
(In Vitro) | In vitro, PLX647 dihydrochloride potently inhibits proliferation of BCR-FMS cells, with an IC50of 92 nM. A corresponding Ba/F3 cell line expressing BCR-KIT is also quite sensitive to PLX647 dihydrochloride, with an IC50of 180 nM. PLX647 dihydrochloride also inhibits endogenous FMS and KIT, as demonstrated by inhibition of the ligand-dependent cell lines M-NFS-60 (IC50=380 nM) and M-07e (IC50=230 nM), which express FMS and KIT, respectively[1].
PLX647 dihydrochloride potently inhibits the growth of FLT3-ITD-expressing MV4-11 cells (IC50=110 nM). PLX647 dihydrochloride displays minimal inhibition of the proliferation of Ba/F3 cells expressing BCR-KDR (IC50=5 μM). PLX647 dihydrochloride inhibits osteoclast differentiation with an IC50of 0.17 μM[1].
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体内研究
(In Vivo) | PLX647 dihydrochloride (40 mg/kg; p.o.; twice daily for 7 days) reduces macrophage accumulation in UUO kidney and blood monocytes[1].
PLX647 dihydrochloride (40 mg/kg; p.o.; male Swiss Webster mice) reduces LPS-induced TNF-α and IL-6 release[1].
PLX647 dihydrochloride (20-80 mg/kg; p.o.; daily or twice daily from 27-41 days) shows effects on collagen-induced arthritis[1].
PLX647 dihydrochloride (30 mg/kg) results in significant inhibition of TRAP5b immunostaining and bone osteolysis. PLX647 dihydrochloride (30 mg/kg BID) is able to prevent bone damage by the tumor cells[1].
| Animal Model: | Male C57BL/6 mice (mouse unilateral ureter obstruction model)[1] | | 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)[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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