Lifirafenib (BGB-283) is a novel and potent Raf Kinase and EGFR inhibitor with IC₅₀ values of 23 and 29 nM for recombinant BRaf^V600E and EGFR, respectively.

Lifirafenib (BGB-283) potently inhibits BRaf^V600E-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harboring BRaf^V600E and EGFR mutation/amplification. In BRaf^V600E colorectal cancer cell lines, Lifirafenib (BGB-283) effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Lifirafenib (BGB-283) treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell line-derived and primary human colorectal tumor xenografts bearing BRaf^V600E mutation^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

478.42

C₂₅H₁₇F₃N₄O₃

1446090-79-4

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL (209.02 mM)

* “≥” means soluble, but saturation unknown.

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

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 (5.23 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.23 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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.23 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.23 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。

• [1]. Tang Z, et al. BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97.

Melanoma, colon, breast, and lung cancer cells are left to attach for 16 hours and then treated with a 10-point dilution series in duplicate. CellTiter-Glo reagent is added in each well. Mixture is mixed on an orbital shaker for 2 minutes to allow cell lysing, followed by 10 minutes incubation at room temperature to allow development and stabilization of luminescent signal. Luminescent signal is measured using PHERAstar FS reader. EC₅₀ values for cell viability are determined^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice: When the average tumor size reaches 110 to 200 mm³, mice are randomized to treatment groups and treated twice per day or once daily by oral gavage (p.o.) with vehicle alone or 2.5 to 30 mg/kg of BGB-283. As control, mice are treated with erlotinib (100 mg/kg qd) or cetuximab (40 mg/kg twice weekly). Lifirafenib (BGB-283) and erlotinib are formulated at the desired concentration as a homogenous suspension in 0.5% (w/v) methylcellulose in purified water. Cetuximab is formulated by diluting the injection solution with saline before dosing^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Tang Z, et al. BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97.