Ralimetinib (LY2228820)
Catalog No.S1494
Molecular Weight(MW): 612.74
Ralimetinib (LY2228820) 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.
6 Customer Reviews
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Relationship of JNK, p38 MAPK, and PI3K activation in TNF-α-induced signaling. Western blot analysis of the effect of another p38 MAPK inhibitor, LY2228820, on TNF-α signaling. HUVECs were pretreated with LY2228820 (10 umol/L) or wortmannin (1 umol/L) for 1 h, followed by stimulation with TNF-α (5 ng/mL) for 15 min (n=2).
Acta Pharmacol Sin 2014 35, 339-50. Ralimetinib (LY2228820) purchased from Selleck.
CD34 expression after 14 days of culture of CB CB CD34+ cells treated with the P38α inhibitor Ly2228820 or vehicle (DMSO; n=3). Error bars represent SEM.
Blood 2012 119, 6255-8. Ralimetinib (LY2228820) purchased from Selleck.
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Cell cycle phase distributions were determined on U87EV and U87PTEN cell treated with B, +/- rapamycin and +/- LY2228820 as shown. Percent apoptotic cells as determined via annexin V staining is also shown below each graph. D were identical to B, except LN229MER-AKT and LN229EV cells induced with 4OHT were used.
Mol Cancer Ther 2011 10, 2244-56. Ralimetinib (LY2228820) purchased from Selleck.
For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of LY2228820 by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 mM HCl and 0.1% Nonidet-40) was added to dissolve the formazan. The absorbance of each well was measured by ELx808 (BioTek, Winooski, VT) or Wallac Victor2 (Perkin-Elmer Life Sciences, Boston, MA) Microplate Reader. Viable cells are presented as percent of control, vehicle-treated cells.
Dr. Yong-Weon Yi from Georgetown University Medical Center. Ralimetinib (LY2228820) purchased from Selleck.
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Cells were treated with 100-mU/mL bTSH with or without 1μM LY2228820. After 5 days, OPN expression (C) was determined by RT-qPCR. OPN secretion was determined by ELISA in cell culture medium. The bars represent the mean ± SEM of 3 experiments with at least 2 biological replicates.
Endocrinology, 2016, 157(5):2173-81. Ralimetinib (LY2228820) purchased from Selleck.
Neuroscience, 2018, 374:61-69. Ralimetinib (LY2228820) purchased from Selleck.
Purity & Quality Control
Choose Selective p38 MAPK Inhibitors
Biological Activity
| Description | Ralimetinib (LY2228820) 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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] |
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| Cell Data |
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| 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] |
Protocol
| Kinase Assay:[1] |
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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. |
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| Cell Research:[2, 3] |
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| Animal Research:[1] |
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Solubility (25°C)
| In vitro | Water | 100 mg/mL warmed (163.2 mM) |
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| DMSO | 4 mg/mL warmed (6.52 mM) | |
| Ethanol | 3 mg/mL (4.89 mM) | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): Saline For best results, use promptly after mixing. |
30 mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 612.74 |
|---|---|
| Formula | C24H29FN6.2CH4O3S |
| CAS No. | 862507-23-1 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
Bio Calculators
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Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02364206 | Active not recruiting | Adult Glioblastoma | Centre Jean Perrin|National Cancer Institute France|ARC Foundation for Cancer Research | June 8 2015 | Phase 1|Phase 2 |
| NCT02364206 | Active not recruiting | 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 |
| NCT02322853 | Terminated | Postmenopausal|Metastatic Breast Cancer | Centre Francois Baclesse|National Cancer Institute France|ARC Foundation for Cancer Research | January 2015 | Phase 2 |
| NCT01663857 | Completed | Epithelial Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Cancer | Eli Lilly and Company | July 2012 | Phase 1|Phase 2 |
| NCT01663857 | Completed | Epithelial Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Cancer | Eli Lilly and Company | July 2012 | Phase 1|Phase 2 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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