Ralimetinib (LY2228820) dimesylate

製品コード：S1494 純度：99.66%

Ralimetinib (LY2228820) dimesylate is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM in a cell-free assay, does not alter p38 MAPK activation. Phase 1/2.

CAS No. 862507-23-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 42900	国内在庫あり
5mg	JPY 25500	国内在庫あり
10mg	JPY 48000	国内在庫あり
50mg	JPY 145500	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

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製品安全説明書

現在のバッチを見る：純度： 99.66%

99.66

Ralimetinib (LY2228820) dimesylate関連製品

関連ターゲット	p38α p38β	もっと見る
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シグナル伝達経路

p38 MAPKシグナル伝達経路

p38 MAPK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	活性情報	PMID
U-87-MG	Function assay	1 μM	reduces tumor-driven cord formation	23335506
CD14+	Function assay	~800 nM	inhibits osteoclastogenesis from CD14 positive cells	18397345
INA-6	Cytoxicity assay	~1000 nM	no significant cytotoxicity	18397345
RPMI-LR5	Cytoxicity assay	~1000 nM	no significant cytotoxicity	18397345
RPMI-Dox40	Cytoxicity assay	~1000 nM	no significant cytotoxicity	18397345
MM.1S	Cytoxicity assay	~1000 nM	no significant cytotoxicity	18397345
U266	Cytoxicity assay	~1000 nM	no significant cytotoxicity	18397345
RPMI-8226	Cytoxicity assay	~1000 nM	no significant cytotoxicity	18397345
INA-6	Kinase assay	~800 nM	inhibits phosphorylation of HSP27	18397345
RPMI-LR5	Kinase assay	~800 nM	inhibits phosphorylation of HSP27	18397345
RPMI-Dox40	Kinase assay	~800 nM	inhibits phosphorylation of HSP27	18397345
MM.1S	Kinase assay	~800 nM	inhibits phosphorylation of HSP27	18397345
U266	Kinase assay	~800 nM	inhibits phosphorylation of HSP27	18397345
RPMI-8226	Kinase assay	~800 nM	inhibits phosphorylation of HSP27	18397345
MDA-MB-231	Function assay	1 μM	reduces tumor-driven cord formation	23335506
A-2780	Function assay	1 μM	reduces tumor-driven cord formation	23335506
SK-OV-3	Function assay	1 μM	reduces tumor-driven cord formation	23335506
LXFA-629	Function assay	1 μM	reduces tumor-driven cord formation	23335506
NCI-H1650	Function assay	1 μM	reduces tumor-driven cord formation	23335506
PC-3	Function assay	1 μM	reduces tumor-driven cord formation	23335506
RAW264.7	Function assay	~20 μM	inhibits Anisomycin-stimulated MK2 phosphorylation with IC50 of 35.3 nM	24356814
mouse peritoneal macrophages	Function assay	~20 μM	LPS/IFN-γ–stimulated TNF-α production with IC50 of 6.3 nM	24356814
A549	Function assay	~20 μM	inhibits LPS-induced CXCL8 production with IC50 of 144.9 nM	24356814
MDA-231	Function assay	~10 μM	suppresses DKK-1 expression	26407843
MCF-7	Function assay	~10 μM	suppresses DKK-1 expression	26407843
MDA-435	Function assay	~10 μM	suppresses DKK-1 expression	26407843
PC3	Function assay	~10 μM	suppresses DKK-1 expression	26913608
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
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生物活性

製品説明

Ralimetinib (LY2228820) dimesylate is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM in a cell-free assay, does not alter p38 MAPK activation. Phase 1/2.

Targets

p38α ^[1]
(Cell-free assay)

7 nM

In Vitro
In vitro	LY2228820 inhibits p38α, as well as the level of phosphoMAPKAPK-2 (pMK2) in RAW 264.7 cells, with IC50 values of 7 nM and 34.3 nM, respectively. Furthermore, LY2228820 inhibits lipopolysaccharide (LPS)-induced TNFα formation in murine peritoneal macrophages, with IC50 of 5.2 nM. ^[1] In multiple myeloma (MM) cells, including INA6, RPMI-8226, U266, and RPMI-Dox40, LY2228820 (200 nM–800 nM) significantly blocks p38MAPK signaling, as revealed by its inhibition on phosphorylation of HSP27, a downstream target of p38MAPK, without affecting the expression level of HSP27. LY2228820 (200 nM–400 nM) enhances cytotoxicity and apoptosis, but LY2228820 alone doesn't inhibit the growth of MM.1S cells. LY2228820 (200 nM–800 nM) also inhibits secretion of IL-6 and MIP-1α in long-term BM stromal cells (LT-BMSCs), BM mononuclear cells (BMMNCs), peripheral blood (PB) CD138⁺, CD138⁻ or PB CD14⁺ cells. LY2228820 (400 nM–800 nM) also blocks osteoclastogenesis from CD14⁺ cells. ^[2]
Kinase Assay	Inhibition of p38α
Kinase Assay	Inhibition of p38α is determined using recombinant human p38α in a standard filter binding protocol using ATP[γ-³³P] and EGFR 21-mer peptide as substrate. Functional inhibition of TNFα in murine peritoneal macrophages is determined using LPS stimulation in the presence of LY2228820. To assess p38α activity in cells more directly, RAW 264.7 cells are treated with LY2228820 and then stimulated with anisomycin. The level of p38α activity is detected using a phosphoMAPKAPK-2 (pMK2) (Thr 334) antibody which reacts with a residue specifically phosphorylated by p38α.
細胞実験	細胞株	MM cells, including INA6, RPMI-8226, U266, and RPMI-Dox40
	濃度	200 nM–800 nM
	反応時間	48 hours
	実験の流れ	MTT assays and APO 2.7 staining are performed to assess cellular proliferation and induction of apoptosis, respectively. Viability is expressed as percent viable cells. Apoptosis in cells is evaluated by APO 2.7 staining. For detection of mitochondrial membrane protein 7A6 expressed in apoptotic cells, cells are incubated with APO 2.7 reagent for 20 min. Expression of APO 2.7 is determined using an EPICS XL flow cytometer.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	p-p38 / p38α / p38β / p-MK2 / MK2 / p-HSP27 / HSP27 p-S6K		23335506

In Vivo
In Vivo	In LPS-induced mice, LY2228820 effectively inhibits the formation of TNFα with a threshold minimum 50% effective dose (TMED₅₀) less than 1 mg/kg. In a rat model of collagen-inducedarthritis (CIA), LY2228820 displays potent effects on paw swelling, bone erosion, and cartilage destruction, with a threshold minimum 50% effective dose (TMED₅₀)of 1.5 mg/kg. ^[1]
動物実験	動物モデル	Lipopolysaccharide (LPS)-induced Balb/c mice
	投与量	0–20 mg/kg
	投与経路	Oral bid dosing for 14 days

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT02860780	Completed	Advanced Cancer\|Metastatic Cancer\|Colorectal Cancer\|Non-small Cell Lung Cancer	Eli Lilly and Company	August 10 2016	Phase 1
NCT02364206	Completed	Adult Glioblastoma	Centre Jean Perrin\|National Cancer Institute France\|ARC Foundation for Cancer Research	June 8 2015	Phase 1\|Phase 2
NCT02322853	Terminated	Postmenopausal\|Metastatic Breast Cancer	Centre Francois Baclesse\|National Cancer Institute France\|ARC Foundation for Cancer Research	January 2015	Phase 2
NCT01393990	Completed	Advanced Cancer	Eli Lilly and Company	September 4 2008	Phase 1

参考
[1] Mader M, et al. Bioorg Med Chem Lett, 2008, 18(1), 179-183. [2] Ishitsuka K, et al. Br J Haematol, 2008, 141(5), 598-606. [3] Ishitsuka K, et al. Oncogene, 2005, 24(38), 5888-5896.

参考

化学情報

分子量	612.74	化学式	C₂₄H₂₉FN₆.2CH₄O₃S
CAS No.	862507-23-1	SDF	Download Ralimetinib (LY2228820) dimesylate SDFをダウンロードする
Smiles	CC(C)(C)CN1C2=C(C=CC(=N2)C3=C(N=C(N3)C(C)(C)C)C4=CC=C(C=C4)F)N=C1N.CS(=O)(=O)O.CS(=O)(=O)O
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:

Water : 100 mg/mL

Ethanol : 20 mg/mL

DMSO : 4 mg/mL ( (6.52 mM)；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。)

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。

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