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)。
| 生物活性 | PLX647 is an orally active, highly specific dualFMSandKITkinase inhibitor, withIC50s 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 exceptFLT3and KDR (IC50s=91 and 130 nM, respectively)[1]. |
体外研究
(In Vitro) | In vitro, PLX647 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, with an IC50of 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[1].
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 IC50of 0.17 μM[1].
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体内研究
(In Vivo) | PLX647 (40 mg/kg; p.o.; twice daily for 7 days) reduces macrophage accumulation in UUO kidney and blood monocytes[1].
PLX647 (40 mg/kg; p.o.; male Swiss Webster mice) reduces LPS-induced TNF-α and IL-6 release[1].
PLX647 (20-80 mg/kg; p.o.; daily or twice daily from 27-41 days) shows effects on collagen-induced arthritis[1].
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[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 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 25 mg/mL(65.38 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.6152 mL | 13.0760 mL | 26.1520 mL | | 5 mM | 0.5230 mL | 2.6152 mL | 5.2304 mL | | 10 mM | 0.2615 mL | 1.3076 mL | 2.6152 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.54 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.54 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.54 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.54 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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