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My CartCAS：862507-23-1
Storage：Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year
Purity：≥98%
Appearance：White to yellow Solid
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| CAS | 862507-23-1 |
| Name | Ralimetinib Dimesylate |
| Molecular Formula | C26H37FN6O6S2 |
| Molecular Weight | 612.74 |
| Solubility | Soluble in Water/DMSO ≥1mg/mL(Need ultrasonic or Water bath) |
| Purity | ≥98% |
| Appearance | White to yellow Solid |
| Storage | Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| MDL | MFCD22572532 |
| SMILES | FC1=CC=C(C=C1)C2=C(NC(C(C)(C)C)=N2)C3=NC4=C(C=C3)N=C(N)N4CC(C)(C)C.OS(C)(=O)=O.OS(C)(=O)=O |
| Target Point | p38 MAPK |
| Passage | MAPK |
| Background | Ralimetinib dimesylate is a selective, ATP-competitive inhibitor of p38 MAPK α/β. |
| Biological Activity | Ralimetinib dimesylate (LY2228820) 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。[1-4] |
| In Vitro | Ralimetinib dimesylate(LY2228820)抑制RAW 264.7细胞中的p38α以及磷酸化MAPKAPK-2(pMK2)的水平，IC50值分别为7 nM和34.3 nM。此外，Ralimetinib dimesylate(LY2228820)抑制脂多糖(LPS)诱导的小鼠腹腔巨噬细胞中TNFα的形成，IC50为5.2 nM [1]。在多发性骨髓瘤(MM)细胞中，包括INA6，RPMI-8226，U266和RPMI-Dox40，Ralimetinib dimesylate(LY2228820)(200 nM-800 nM)显著阻断p38MAPK信号传导，正如其对HSP27磷酸化的抑制所揭示的，p38MAPK的下游靶标，不影响HSP27的表达水平。Ralimetinib dimesylate(LY2228820)(200nM-400nM)增强硼替佐米诱导的细胞毒性和细胞凋亡，但单独的Ralimetinib dimesylate(LY2228820)不抑制MM.1S细胞的生长。 Ralimetinib dimesylate(LY2228820)(200 nM-800 nM)也抑制长期BM基质细胞(LT-BMSCs)，BM单核细胞(BMMNCs)，外周血(PB)CD138 +中IL-6和MIP-1α的分泌，CD138-或PB CD14 +细胞。 Ralimetinib dimesylate(LY2228820)(400 nM-800 nM)也可阻断CD14 +细胞的破骨细胞生成[2]。 |
| In Vivo | 在LPS诱导的小鼠中，Ralimetinib dimesylate(LY2228820)有效抑制TNFα的形成，阈值最小50％有效剂量(TMED50)小于1mg/kg。在胶原诱导的关节炎(CIA)的大鼠模型中，Ralimetinib dimesylate(LY2228820)对爪肿胀，骨侵蚀和软骨破坏显示出有效作用，阈值最小50％有效剂量(TMED50)为1.5 mg/kg [1] 。Ralimetinib dimesylate(LY2228820)在植入B16-F10黑素瘤的小鼠中以剂量依赖性方式(TED50 = 1.95mg/kg，TED70 = 11.17mg/kg)抑制肿瘤磷酸化-MK2。 Ralimetinib dimesylate(LY2228820)抑制MK2磷酸化：小鼠体内TED50 = 1.01 mg/kg(化合物暴露约100 nM)，人体外PC50 =0.12μM与小鼠或人PBMC [3]。 |
| Animal Experiment | 在补充有1-谷氨酰胺，高葡萄糖和10％FBS(GIBCO 11965-092)的Dulbecco's改良Eagle培养基中培养鼠B16-F10黑素瘤细胞。 C57/bl6小鼠在后侧植入B16-F10细胞(2×106)，当肿瘤大小达到约200mm3时，在1％羧甲基纤维素/0.25%吐温80中口服Ralimetinib dimesylate 。给药后2小时，切除肿瘤。 |
| Kinase Experiment | 在LY2228820存在下使用LPS刺激测定鼠腹膜巨噬细胞中TNFα的功能性抑制。为了更直接地评估细胞中的p38α活性，用LY2228820处理RAW 264.7细胞，然后用茴香霉素刺激。使用磷酸MTAPAPK-2(pMK2)(Thr 334)抗体检测p38α活性水平，该抗体与p38α特异性磷酸化的残基反应。 |
| Data Literature Source | [1]. Mader M，et al. Imidazolyl benzimidazoles and imidazo[4，5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties. Bioorg Med Chem Lett，2008，18(1)，179-183. [2]. Ishitsuka K，et al. p38 mitogen-activated protein kinase inhibitor LY2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications. Br J Haematol，2008，141(5)，598-606. [3]. Campbell RM，et al. Characterization of LY2228820 dimesylate，a potent and selective inhibitor of p38 MAPK with antitumor activity. Mol Cancer Ther. 2014 Feb;13(2):364-74. [4]. Zhang Y，et al. PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. EBioMedicine. 2015 Nov 19;2(12):1944-56. |
| Unit | Bottle |
| Specification | 5mg 10mg 25mg |
Ralimetinib dimesylate是一种选择性，ATP竞争性的 p38 MAPK α/β 抑制剂。
Remark：These protocols are for reference only. Solarbio does not independently validate these methods.
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