LY3009120 (DP-4978) is a panRAFinhibitor which inhibitsBRAF^V600E,BRAF^WTand CRAF^WTwithIC₅₀s of 5.8, 9.1 and 15 nM, respectively.

In the whole-cell based KiNativ assay, LY3009120 shows affinity to each RAF isoform with the IC₅₀of 44, 31-47 and 42 nM for ARAF, BRAF and CRAF respectively. LY3009120 exhibits anti-proliferative effects on cell lines harboring BRAF^V600E, KRAS^G13and KRAS^G12mutations. LY3009120 (1 μM) inhibits the phosphorylation of both MEK1/2 and ERK1/2 in cell lines with high basal levels of pMEK1/2 and pERK1/2 (RKO and HCT 116)^[1]. LY3009120 shows inhibitory effect on tumor cells such as BxPC-3, NCI-H2405 and OV-90 cell lines. LY3009120 (0.01 μM) demonstrates potent and dose-dependent inhibition of phospho-MEK and ERK in all three cell lines. LY3009120 demonstrates a concentration-dependent cell growth inhibition with IC₅₀values of 0.04, 0.087, and 0.007 μM against H2405, BxPC-3, and OV-90 cells, respectively^[2]. LY3009120 inhibits BRAF^WT, CRAF^WT, BRAF^V600E, and BRAF^V600E+G468Awith the IC₅₀values of 9.1, 15, 5.8, and 17 nM, respectively. LY3009120 induces BRAF-CRAF dimerization but inhibits the phosphorylation of downstream MEK and ERK. LY3009120 also inhibits various forms of RAF dimers including BRAF or CRAF homodimers^[3]. LY3009120 gives only very minor activation at very low doses, with near complete inhibition of phospho-ERK at concentrations above 100 nM^[4].

LY3009120 (20 mg/kg bid) displays significant activity in in vivo BRAF^mutand KRAS^mutCRC xenograft models. In Colo 205 xenografts (BRAF^mut), LY3009120 results in statistically significant tumor regression, while treatment of HCT 116 xenografts (KRAS^mut) results in statistically significant inhibition of tumor growth. LY3009120 treatment reduces pMEK1/2 in all HT-29 xenografts and reduces pERK1/2 in the majority of HT-29 xenografts^[1]. LY3009120 (15 or 30 mg/kg) achieves almost complete tumor growth regression, and inhibits downstream phospho-MEK and ERK by approximately 70% and 60%, respectively, in the H2405 model^[2].

424.51

Solid

C₂₃H₂₉FN₆O

1454682-72-4

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 38 mg/mL(89.51 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℃, 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。

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： 5% DMSO    95% (20%SBE-β-CDin saline)

  Solubility: 2.5 mg/mL (5.89 mM); Suspended solution; Need ultrasonic