| 產品描述： | PLX647 is an orally active, highly specific dual FMS and KIT kinase inhibitor, with IC50s 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 (IC50s=91 and 130 nM, respectively) |
| 靶點： |
c-Fms;c-Kit |
| 體外研究： |
In vitro, PLX647 potently inhibits proliferation of BCR-FMS cells, with an IC50 of 92 nM. A corresponding Ba/F3 cell line expressing BCR-KIT is also quite sensitive to PLX647, with an IC50 of 180 nM. PLX647 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. PLX647 potently inhibits the growth of FLT3–ITD-expressing MV4-11 cells (IC50=110 nM). PLX647 displayed minimal inhibition of the proliferation of Ba/F3 cells expressing BCR–KDR (IC50=5 μM). PLX647 inhibits osteoclast differentiation with an IC50 of 0.17 μM |
| 體內研究： |
PLX647 (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. 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. |
| 參考文獻： |
1. Zhang C, et al. Design and pharmacology of a highly specific dual FMS and KIT kinase inhibitor. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5689-94. 2. Louvet C, et al. Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18895-900. |
| 溶解性： |
soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.615 ml |
13.076 ml |
26.152 ml |
| 5 mM |
0.523 ml |
2.615 ml |
5.23 ml |
| 10 mM |
0.262 ml |
1.308 ml |
2.615 ml |
| 50 mM |
0.052 ml |
0.262 ml |
0.523 ml |
|
| 注意： |
部分產品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。 |
上海工商
危險品化學品經營許可證（不帶存儲）
營業執照(三證合一)
北京