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Ralimetinib dimesylate
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Ralimetinib dimesylate图片
CAS NO:862507-23-1
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品名称
LY2228820 dimesylate
产品介绍
Ralimetinib dimesylate (LY2228820 dimesylate) 是一种选择性,ATP竞争性的p38 MAPK α/β抑制剂,IC50分别为5.3 和 3.2 nM。
生物活性

Ralimetinib dimesylate (LY2228820 dimesylate) is a selective, ATP-competitive inhibitor ofp38 MAPKα/βwithIC50s of 5.3 and 3.2 nM, respectively. Ralimetinib (LY2228820) selectively inhibits phosphorylation of MK2 (Thr334), with no effect on phosphorylation of p38a MAPK,JNK, ERK1/2, c-Jun, ATF2, orc-Myc.

IC50& Target[3]

p38β MAPK

3.2 nM (IC50)

p38α MAPK

5.3 nM (IC50)

体外研究
(In Vitro)

Ralimetinib dimesylate inhibits p38α, as well as the level of phosphoMAPKAPK-2 (pMK2) in RAW 264.7 cells, with IC50values of 7 nM and 34.3 nM, respectively. Furthermore, Ralimetinib dimesylate inhibits lipopolysaccharide (LPS)-induced TNFα formation in murine peritoneal macrophages, with IC50of 5.2 nM[1]. In multiple myeloma (MM) cells, including INA6, RPMI-8226, U266, and RPMI-Dox40, Ralimetinib dimesylate (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. Ralimetinib dimesylate (200 nM-400 nM) enhances bortezomib-induced cytotoxicity and apoptosis, but Ralimetinib dimesylate alone doesn't inhibit the growth of MM.1S cells. Ralimetinib dimesylate (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. Ralimetinib dimesylate (400 nM-800 nM) also blocks osteoclastogenesis from CD14+cells[2].

体内研究
(In Vivo)

In LPS-induced mice, Ralimetinib dimesylate 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), Ralimetinib dimesylate 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]. Ralimetinib dimesylate inhibits tumor phospho-MK2 in a dose-dependent manner (TED50=1.95 mg/kg, TED70=11.17 mg/kg) in mice implanted with B16-F10 melanoma. Ralimetinib dimesylate inhibits MK2 phosphorylation: mouse in vivo TED50=1.01 mg/kg (compound exposure approximately 100 nM) and human ex vivo IC50=0.12 μM with either mouse or human PBMC[3].

Clinical Trial
分子量

612.74

性状

Solid

Formula

C26H37FN6O6S2

CAS 号

862507-23-1

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据
In Vitro: 

DMSO : 61 mg/mL(99.55 mM;Need ultrasonic and warming)

H2O : ≥ 33.33 mg/mL(54.40 mM)

*"≥" means soluble, but saturation unknown.

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.6320 mL8.1601 mL16.3201 mL
5 mM0.3264 mL1.6320 mL3.2640 mL
10 mM0.1632 mL0.8160 mL1.6320 mL
*

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 (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

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: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (4.08 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.08 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20%SBE-β-CDin saline)

    Solubility: ≥ 2.5 mg/mL (4.08 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.08 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90%corn oil

    Solubility: ≥ 2.5 mg/mL (4.08 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.08 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在本网站选购。