LY3009120

別名：DP-4978

製品コード：S7842 純度：99.08%

LY03009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. LY03009120 induces autophagy. Phase 1.

CAS No. 1454682-72-4

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 71500	国内在庫あり
100mg	JPY 149500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（52）

製品安全説明書

現在のバッチを見る：純度： 99.08%

99.08

LY3009120関連製品

関連ターゲット	C-Raf/Raf-1 B-Raf A-raf	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library Anti-alzheimer Disease Compound Library	もっと見る

シグナル伝達経路

Rafシグナル伝達経路

Raf阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
HCT116	Function assay	<100 nM		Paradoxical activation of RAS/RAF/MEK signaling pathway in human HCT116 cells expressing wild type BRAF assessed as ERK phosphorylation at <100 nM	25965804
A375	Function assay		15 mins	Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.042μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.039μM.	25965804
A375	Function assay		72 hrs	Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay, IC50=0.037μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.031μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.02μM.	25965804
A375	Antiproliferative assay		72 hrs	Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay, IC50=0.0092μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.044μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.061μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.091μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.098μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.1μM.	25965804
HCT116	Antiproliferative assay		67 hrs	Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay, IC50=0.22μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.29μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.31μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.38μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.39μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.45μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.47μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.8μM.	25965804
A375	Function assay		15 mins	Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.97μM.	25965804
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.1μM.	30529543
SK-MEL-2	Antiproliferative assay		72 hrs	Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.2μM.	30529543
A375	Antiproliferative assay		72 hrs	Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.3μM.	30529543
SW579	Antiproliferative assay		72 hrs	Antiproliferative activity against human SW579 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM.	30529543
HT-29	Antiproliferative assay		72 hrs	Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM.	30529543
HepG2	Antiproliferative assay		72 hrs	Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay, IC50=2.6μM.	30529543
HCT116	Function assay			Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA, IC50=0.15μM.	25965804
A375	Function assay			In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as plasma concentration required to inhibit ERK phosphorylation by 50%, INH=0.165μM.	25965804
A375	Function assay			Inhibition of desthiobiotin-ATP acylphosphate probe binding to B-Raf in human A375 cells by MS analysis, IC50=0.031μM.	30529543
A375	Function assay			Inhibition of desthiobiotin-ATP acylphosphate probe binding to C-Raf in human A375 cells by MS analysis, IC50=0.042μM.	30529543
A375	Function assay			Inhibition of desthiobiotin-ATP acylphosphate probe binding to A-Raf in human A375 cells by MS analysis, IC50=0.044μM.	30529543
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生物活性

製品説明

LY03009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. LY03009120 induces autophagy. Phase 1.

Targets

C-Raf ^[1] (Cell-free assay)	BRAF(V600E) ^[1] (Cell-free assay)	BRAF WT ^[1] (Cell-free assay)
4.3 nM	5.8 nM	15 nM

In Vitro
In vitro	LY3009120 inhibits the cell growth of A375 and HCT116 cells with the IC50 of 9.2 and 220 μM, respectively. LY3009120 inhibits the tyrosine kinase KDR with the IC50 of 3.9 μM.^[1]
Kinase Assay	Kinase activity measurement using KiNativ assays
Kinase Assay	Compounds are screened in A375 cell lysates using the ATP-based probe at 5 µM. IC50 values are reported in micromolar units. Cell pellets are resuspended in four volumes of lysis buffer [25 mM Tris pH 7.6, 150 mM NaCl, 1% CHAPS, 1% Tergitol NP-40 type, 1% v/v phosphatase inhibitor cocktail II], sonicated using a tip sonicator, and dounce homogenized. Lysates are cleared by centrifugation at 100,000 g for 30 min. The cleared lysates are filtered through a 0.22 μM syringe filter, and gel filtered into reaction buffer [20 mM Hepes pH 7.8, 150 mM NaCl, 0.1% triton X-100, 1% v/v phosphatase inhibitor cocktail II]. MnCl2 is then added to the lysate to a final concentration of 20 mM prior to inhibitor treatment and probe labeling. Final inhibitor concentrations used for IC50 determinations are 10, 1, 0.1, and 0.01 μM. ATP competition experiments are performed at 1,000, 100, 10, and 1 μM ATP. All inhibitor treatments are performed at room temperature.
細胞実験	細胞株	A375 and HCT116 cells
	濃度	0.51 μM
	反応時間	67 h
	実験の流れ	Brieﬂy, cells are grown in DMEM high glucose supplemented with 10% characterized fetal bovine serum and 1% penicillin/streptomycin/L -glutamine at 37℃, 5% CO₂, and 95% humidity. Cells are allowed to expand until 70-95% conﬂuency. A serial dilution of test compound is dispensed into a 384-well black clear bottom plate. 625 cells are added per well in 50 μL of complete growth medium. Plates are incubated for 67 h at 37℃, 5% CO2 , and 95% humidity. Then, 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℃, 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 software to calculate IC 50 values.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	Beclin-1 / Mcl-1 / LC3 / p62 p-EGFR / EGFR / p-BRAF / BRAF / p-CRAF / CRAF / p-MEK / MEK / p-AKT / AKT		28382170

In Vivo
In Vivo	In rats bearing BRAF V600E ST019VR PDX tumors, LY3009120 (15 or 30 mg/kg, p.o.) shows a dose-dependent tumor growth inhibition. In nude rats bearing A375 xenograft, single dose oral treatment with LY3009120 (3 to 50 mg/kg, p.o.) shows a dose dependent inhibition of phospho-ERK, with a dose for 50% inhibition of phospho-ERK (EC50) of 4.36 mg/kg, with plasma concentration to achieve 50% inhibition of phospho-ERK (EC50) of 68.9 ng/mL or 165 nM.^[1]
動物実験	動物モデル	Female NIH nude rats bearing BRAF V600E ST019VR PDX tumors
	投与量	30 mg/kg
	投与経路	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT02014116	Terminated	Neoplasms\|Neoplasm Metastasis\|Melanoma\|Carcinoma Non-Small-Cell Lung\|Colorectal Neoplasms	Eli Lilly and Company	November 26 2013	Phase 1

参考
[1] Henry JR, et al. J Med Chem. 2015, 58(10), 4165-4179. [2] Patricelli MP, et al. Chem Biol.?011, 18(6), 699-710.

参考

化学情報

分子量	424.51	化学式	C₂₃H₂₉FN₆O
CAS No.	1454682-72-4	SDF	Download LY3009120 SDFをダウンロードする
Smiles	CC1=CC(=C(C=C1C2=C(N=C3C(=C2)C=NC(=N3)NC)C)NC(=O)NCCC(C)(C)C)F
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 20 mg/mL ( (47.11 mM)； Warmed with 50℃ water bath; 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

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Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

質問1:
I am trying to figure out solubility of the drug LY3009120 Catalog #7842 for in vivo studies. I need some details on the formulation and how it is made to dissolve the chemical?

回答
It can dissolve in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O at 1 mg/ml clearly, and in 0.5% CMC Na at 30 mg/ml as a suspension.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):