LY3009120 (Synonyms: DP-4978)

目录号: HY-12558 纯度: 98.66%: Data Sheet SDS COA 产品使用指南
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LY3009120 (DP-4978) 是泛 RAF 抑制剂，其抑制BRAF^V600E，BRAF^WT 和CRAF^WT 的 IC₅₀ 分别为 5.8，9.1和15 nM。

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LY3009120 Chemical Structure

CAS No. : 1454682-72-4

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规格	价格	是否有货
10 mM * 1 mL in DMSO	￥794	In-stock
1 mg	￥386	In-stock
5 mg	￥850	In-stock
10 mg	￥1350	In-stock
25 mg	￥2430	In-stock
50 mg	￥3645	In-stock
100 mg	￥5285	In-stock
200 mg	现货	询价
500 mg		询价
1 g		询价

or 大包装询价

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Customer Review

MCE 顾客使用本产品发表的 14 篇科研文献

: LY3009120 purchased from MCE. Usage Cited in: Clin Sci (Lond). 2019 Apr 16;133(8):919-932. [Abstract]; Colonic proteins on day 7 are tested by immunoblotting to detect p-MLKL, MLKL and cleaved caspase-3 with corresponding antibodies. GAPDH is used as an internal control. Three individual mice from each group are shown.

: LY3009120 purchased from MCE. Usage Cited in: Clin Sci (Lond). 2019 Apr 16;133(8):919-932. [Abstract]; LY3009120 decreases phosphorylation of RIPK1, RIPK3 and MLKL in T/S/Z treated HT-29 cells. HT-29 cells are pretreated with DMSO or LY3009120 for 1 hour, then treated with T/S/Z for 0, 2, 4 and 6 hours, respectively.

: LY3009120 purchased from MCE. Usage Cited in: Oncogene. 2018 Oct;37(43):5719-5734. [Abstract]; BRAF mutants with in-frame β3-αC loop deletions have approximate sensitivities to RAF dimer inhibitor, LY3009120.

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B-Raf C-Raf Raf

生物活性
实验参考方法
纯度 & 产品资料
参考文献

生物活性

LY3009120 (DP-4978) is a pan RAF inhibitor which inhibits BRAF^V600E, BRAF^WT and CRAF^WT with IC₅₀s of 5.8, 9.1 and 15 nM, respectively.

IC₅₀ & Target^[1]

BRaf^V600E

5.8 nM (IC₅₀)

Braf

9.1 nM (IC₅₀)

CRAF

15 nM (IC₅₀)

细胞效力
(Cellular Effect)

Cell Line	Type	Value	Description	References
A-375	IC₅₀	0.0092 μM Compound: 13, LY3009120	Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay	[PMID: 25965804]
A-375	IC₅₀	0.037 μM Compound: 13, LY3009120	Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay	[PMID: 25965804]
A-375	IC₅₀	0.3 μM Compound: LY3009120	Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
A-375	IC₅₀	100 nM Compound: 13, LY3009120	Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	20 nM Compound: 13, LY3009120	Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	28.3 nM Compound: 1; LY3009120	Antiproliferative activity against human A-375 cells harboring BRAF mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay Antiproliferative activity against human A-375 cells harboring BRAF mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay	[PMID: 33780623]
A-375	IC₅₀	290 nM Compound: 13, LY3009120	Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	31 nM Compound: 13, LY3009120	Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	310 nM Compound: 13, LY3009120	Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	380 nM Compound: 13, LY3009120	Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	39 nM Compound: 13, LY3009120	Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	390 nM Compound: 13, LY3009120	Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	EC₅₀	4.36 mg/kg Compound: 13, LY3009120	In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as inhibition of ERK phosphorylation by ELISA In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as inhibition of ERK phosphorylation by ELISA	[PMID: 25965804]
A-375	IC₅₀	42 nM Compound: 13, LY3009120	Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	44 nM Compound: 13, LY3009120	Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	450 nM Compound: 13, LY3009120	Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	470 nM Compound: 13, LY3009120	Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	61 nM Compound: 13, LY3009120	Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	800 nM Compound: 13, LY3009120	Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	91 nM Compound: 13, LY3009120	Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	970 nM Compound: 13, LY3009120	Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	98 nM Compound: 13, LY3009120	Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A549	IC₅₀	45.6 nM Compound: 1; LY3009120	Synergistic antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs in presence of 100 nM cobimetinib by Click-iT EdU cell proliferation imaging assay Synergistic antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs in presence of 100 nM cobimetinib by Click-iT EdU cell proliferation imaging assay	[PMID: 33780623]
A549	IC₅₀	545 nM Compound: 1; LY3009120	Antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay Antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay	[PMID: 33780623]
HCT-116	IC₅₀	0.15 μM Compound: 13, LY3009120	Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA	[PMID: 25965804]
HCT-116	IC₅₀	0.22 μM Compound: 13, LY3009120	Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay	[PMID: 25965804]
HepG2	IC₅₀	2.6 μM Compound: LY3009120	Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
HT-29	IC₅₀	0.9 μM Compound: LY3009120	Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
MV4-11	IC₅₀	0.1 μM Compound: LY3009120	Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
SK-MEL-2	IC₅₀	0.2 μM Compound: LY3009120	Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]

体外研究
(In Vitro)

在基于全细胞的 KiNativ 测定中，LY3009120 对每种 RAF 亚型均表现出亲和力，对 ARAF、BRAF 和 CRAF 的 IC₅₀ 分别为 44、31-47 和 42 nM。LY3009120 对携带 BRAF^V600E、KRAS^G13 和 KRAS^G12 突变的细胞系表现出抗增殖作用。LY3009120 (1 μM) 可抑制 pMEK1/2 和 pERK1/2 基础水平较高的细胞系 (RKO 和 HCT 116) 中 MEK1/2 和 ERK1/2 的磷酸化^[1]。 LY3009120 对肿瘤细胞（如 BxPC-3、NCI-H2405 和 OV-90 细胞系）有抑制作用。LY3009120 (0.01 μM) 在这三种细胞系中均表现出对磷酸化 MEK 和 ERK 的强效和剂量依赖性抑制作用。LY3009120 对 H2405、BxPC-3 和 OV-90 细胞表现出浓度依赖性的细胞生长抑制作用，IC₅₀ 值分别为 0.04、0.087 和 0.007 μM^[2]。 LY3009120 抑制 BRAF^WT、CRAF^WT、BRAF^V600E 和 BRAF^V600E+G468A，IC₅₀ 值分别为 9.1、15、5.8 和 17 nM。LY3009120 诱导 BRAF-CRAF 二聚化，但抑制下游 MEK 和 ERK 的磷酸化。LY3009120 还抑制各种形式的 RAF 二聚体，包括 BRAF 或 CRAF 同型二聚体^[3]。 LY3009120 在极低剂量下仅产生非常轻微的激活作用，而当浓度高于 100 nM^[4] 时几乎完全抑制磷酸化 ERK。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

LY3009120 (20 mg/kg bid) 在体内 BRAF^mut 和 KRAS^mut CRC 异种移植模型中表现出显著活性。在 Colo 205 异种移植瘤 (BRAF^mut) 中，LY3009120 可显著降低肿瘤生长，且具有统计学意义；而在 HCT 116 异种移植瘤 (KRAS^mut) 中，LY3009120 可显著抑制肿瘤生长，且具有统计学意义。LY3009120 可降低所有 HT-29 异种移植瘤中的 pMEK1/2，并降低大多数 HT-29 异种移植瘤中的 pERK1/2^[1]。
在 H2405 模型中，LY3009120（15 或 30 mg/kg）可使肿瘤生长几乎完全消退，并分别抑制下游磷酸化 MEK 和 ERK 约 70% 和 60%^[2]。 mg/kg) 会产生缓慢发展的高热症，注射后 130 min 时最高升高 1.8°C。SR59230A (0.5 mg/kg) 对 MDMA 引起的缓慢发展的高热症有轻微但明显的减弱作用。SR59230A (5 mg/kg) 对 MDMA 表现出明显的早期低温反应^[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

424.51

Formula

C₂₃H₂₉FN₆O

CAS 号

1454682-72-4

性状

固体

颜色

Light yellow to khaki

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	2 years
	-20°C	1 year

溶解性数据

细胞实验：

DMSO 中的溶解度 : ≥ 38 mg/mL (89.51 mM; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

* "≥" means soluble, but saturation unknown.

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.3557 mL	11.7783 mL	23.5566 mL
5 mM	0.4711 mL	2.3557 mL	4.7113 mL
10 mM	0.2356 mL	1.1778 mL	2.3557 mL

查看完整储备液配制表

* 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, 2 years; -20°C, 1 year。-80°C储存时，请在2年内使用， -20°C储存时，请在1年内使用。

摩尔计算器
稀释计算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

浓度 _(start)

体积 _(start)

浓度 _(final)

体积 _(final)

动物实验：

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

方案一

请依序添加每种溶剂： 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.89 mM); 悬浊液; 超声助溶

动物溶解方案计算器

请输入动物实验的基本信息：

给药剂量

mg/kg

动物的平均体重

每只动物的给药体积

μL

动物数量

只

由于实验过程有损耗，建议您多配一只动物的量

请输入您的动物体内配方组成：

DMSO +

Tween-80 +

Saline

如果您的动物是免疫缺陷鼠或者体弱鼠，建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。

方案所需 助溶剂 包括：DMSO，，均可在 MCE 网站选购。，Tween 80，均可在 MCE 网站选购。

计算结果

工作液所需浓度 : mg/mL

储备液配制方法 : mg 药物溶于 μL DMSO（母液浓度为 mg/mL）。

您所需的储备液浓度超过该产品的实测溶解度，以下方案仅供参考，如有需要，请与 MCE 中国技术支持联系。

动物实验体内工作液的配制方法 : 取 μL DMSO 储备液，加入 μL 。 μL ，混合均匀至澄清，再加 μL Tween 80，混合均匀至澄清，再加 μL 生理盐水。

连续给药周期超过半月以上，请谨慎选择该方案。

请确保第一步储备液溶解至澄清状态，从左到右依次添加助溶剂。您可采用超声加热（超声清洗仪，建议频次 20-40 kHz），涡旋吹打等方式辅助溶解。

纯度 & 产品资料

纯度: 98.66%

选择批次：

Data Sheet (642 KB) SDS (393 KB)

COA (282 KB)

产品使用指南 (1538 KB)

参考文献

[1]. Vakana E, et al. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251-9266 [Content Brief]

[2]. Chen SH, et al. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov. 2016 Mar;6(3):300-15 [Content Brief]

[3]. Peng SB, et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384-98 [Content Brief]

[4]. Henry JR, et al. Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumo [Content Brief]

Cell Assay ^[4]	Briefly, cells are grown in McCoy’s 5A supplemented with 10% characterized fetal bovine serum at 37°C, 5% CO₂, and 95% humidity. Cells are allowed to expand until 75-90% confluency at which point they are subcultured or harvested for assay use. A serial dilution of test compound is dispensed into a 384-well black clear bottom plate in triplicate. Six-hundred-twenty-five cells are added per well in 50 μL of complete growth medium in the 384-well plate. Plates are incubated for 67 h at 37°C, 5% CO₂, and 95% humidity. At the end of the incubation period, 10 μL of a 440 μM solution of resazurin in PBS is added to each well of the plate and plates are incubated for an additional 5 h at 37°C, 5% CO₂, and 95% humidity. Plates are read on a Synergy2 reader using an excitation of 540 nm and an emission of 600 nm. Data are analyzed using Prism softwareto calculate IC₅₀ values. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	Briefly, 5×10⁶ to 10×10⁶ tumor cells in a 1:1 Matrigel mix (0.2 mL total volume) are injected subcutaneously into the right hind flank of female NIH nude rats. After tumors reach a desired size of approximately 300 mm³, animals are randomized into groups of 8 for efficacy studies. Drugs (LY3009120 or PLX4032) are administered orally (gavage) in 0.6-mL volume of vehicle with the dose schedules. Tumor growth and body weight are monitored over time to evaluate efficacy and signs of toxicity. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献	[1]. Vakana E, et al. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251-9266 [Content Brief] [2]. Chen SH, et al. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov. 2016 Mar;6(3):300-15 [Content Brief] [3]. Peng SB, et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384-98 [Content Brief] [4]. Henry JR, et al. Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumo [Content Brief]

LY3009120 相关分类

完整储备液配制表

可选溶剂	浓度溶剂体积质量	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.3557 mL	11.7783 mL	23.5566 mL	58.8914 mL
	5 mM	0.4711 mL	2.3557 mL	4.7113 mL	11.7783 mL
	10 mM	0.2356 mL	1.1778 mL	2.3557 mL	5.8891 mL
	15 mM	0.1570 mL	0.7852 mL	1.5704 mL	3.9261 mL
	20 mM	0.1178 mL	0.5889 mL	1.1778 mL	2.9446 mL
	25 mM	0.0942 mL	0.4711 mL	0.9423 mL	2.3557 mL
	30 mM	0.0785 mL	0.3926 mL	0.7852 mL	1.9630 mL
	40 mM	0.0589 mL	0.2945 mL	0.5889 mL	1.4723 mL
	50 mM	0.0471 mL	0.2356 mL	0.4711 mL	1.1778 mL
	60 mM	0.0393 mL	0.1963 mL	0.3926 mL	0.9815 mL
	80 mM	0.0294 mL	0.1472 mL	0.2945 mL	0.7361 mL

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

LY30091201454682-72-4DP-4978LY 3009120LY-3009120DP4978DP 4978RafAutophagyRaf kinasesInhibitorinhibitorinhibit

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LY3009120 (Synonyms: DP-4978)

Customer Review

MCE 顾客使用本产品发表的 14 篇科研文献

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生物活性

实验参考方法

纯度 & 产品资料

参考文献

摩尔计算器

稀释计算器

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LY3009120 (Synonyms: DP-4978)

Customer Review

LY3009120 相关抗体

MCE 顾客使用本产品发表的 14 篇科研文献

LY3009120 相关产品

•相关化合物库:

•同靶点产品:

•同靶点蛋白产品:

查看 Raf 亚型特异性产品:

生物活性

实验参考方法

纯度 & 产品资料

参考文献

LY3009120 相关抗体:

摩尔计算器

稀释计算器

LY3009120 相关分类

完整储备液配制表

Keywords:

您最近查看的产品:

Request for HNMR Report

Request for HNMR Report

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z