Antibodies
LY2228820
- 貨號 Cat. No.
- S1494
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
LY2228820
LY2228820 is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM, does not alter p38 MAPK activation. Phase 1/2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | LY2228820 is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM, does not alter p38 MAPK activation. Phase 1/2. | |||||
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| Targets | p38α | |||||
| IC50 | 7 nM [1] | |||||
| 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] | |||||
| 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] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| 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 Assay: [2, 3]
| Cell lines | MM cells, including INA6, RPMI-8226, U266, and RPMI-Dox40 |
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| Concentrations | 200 nM–800 nM |
| Incubation Time | 48 hours |
| Method | 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. |
Animal Study: [1]
| Animal Models | Lipopolysaccharide (LPS)-induced Balb/c mice |
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| Dosages | 0–20 mg/kg |
| Administration | Oral bid dosing for 14 days |
| Solubility | Saline, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01393990 | Active, not recruiting | Advanced Cancer | Eli Lilly and Company | 2008-08 | Phase 1 |
| NCT01663857 | Recruiting | Epithelial Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Cancer | Eli Lilly and Company | 2012-09 | Phase 1|Phase 2 |
Chemical Information
| Molecular Weight (MW) | 612.74 |
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| Formula | C24H29FN6.2CH4O3S |
| CAS No. | 862507-23-1 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 35 mg/mL (57 mM) |
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| Water | 123 mg/mL (200 mM) | ||
| Ethanol | 3 mg/mL (4 mM) | ||
| In vivo | Saline, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * 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 Name | 5-(2-tert-butyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-neopentyl-3H-imidazo[4,5-b]pyridin-2-amine dimethanesulfonate |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.61274 | 6.1274 | 12.2548 | 18.3822 |
Customer Reviews (2)
 Click to enlarge | Rating | |
| Source | Dr. Yong-Weon Yi from Georgetown University Medical Center.LY2228820 purchased from Selleck | |
| Method | MTT assays | |
| Cell Lines | SUM149PT cells | |
| Concentrations | 0.12-10 μM | |
| Incubation Time | 72 h | |
| Results |
Product Citations (5)
RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion. [Baudet A, et al. Blood 2012;119(26):6255-8]
Inhibition of SAPK2/p38 enhances sensitivity to mTORC1 inhibition by blocking IRES-mediated translation initiation in glioblastoma. [Cloninger C, et al. Mol Cancer Ther 2011;10(12):2244-56]
Acyl-CoA Synthetase 1 is Induced by Gram-Negative Bacteria and Lipopolysaccharide and is Required for Phospholipid Turnover in Stimulated Macrophages. [Rubinow KB, et al. J Biol Chem 2013;288(14):9957-70]
