Ralimetinib (LY2228820) dimesylate

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.

Ralimetinib (LY2228820) dimesylate化学構造

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
JPY 25500 国内在庫あり
JPY 48000 国内在庫あり
JPY 145500 国内在庫あり
JPY 448500 国内在庫なし(納期7~10日)

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Ralimetinib (LY2228820) dimesylate関連製品

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 Incubation Time 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 bortezomib-induced 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
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
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
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

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

In vitro
Batch:

Water : 123 mg/mL

DMSO : 35 mg/mL ( (57.12 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。)

Ethanol : 3 mg/mL

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

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)

mg/kg g μL

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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