N/A
中文名称:
N/A
中文同义词:
FMS/KIT双重抑制剂(PLX647)
英文名称:
PLX647
英文同义词:
PLX647;PLC647;5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-N-[[4-(trifluoromethyl)phenyl]methyl]-2-pyridinamine;2-Pyridinamine, 5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-N-[[4-(trifluoromethyl)phenyl]methyl]-;PLX 647;PLX-647;CS-1696;[5-[(1H-Pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-yl](4-trifluoromethylbenzyl)amine
CAS号:
873786-09-5
分子式:
C21H17F3N4
分子量:
382.38
EINECS号:
相关类别:
细胞生物学试剂;小分子抑制剂;小分子抑制剂，天然产物;Inhibitors
Mol文件:
873786-09-5.mol
储存条件
2-8°C
溶解度
DMSO: soluble20mg/mL, clear
形态
powder
颜色
white to beige
生物活性
PLX647 是一种高度特异性的，具有口服活性的 FMS 和 KIT 双激酶抑制剂，IC50 分别为 28 和 16 nM。PLX647 (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)。
体外研究
In 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.
体内研究
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.
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.
危险品标志
Xi
危险类别码
36/37/38
安全说明
36/37/39
WGK Germany
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