My cart
In the shopping cart is not goods, to choose and buy!
  • Product Name
  • Size
  • Quantity
  • Amount
    Selected items : 0 pieces Total : CHECK OUT()
    Ralimetinib dimysylate (LY2228820 dimysylate)
    Ralimetinib dimysylate (LY2228820 dimysylate)

    Price:
    Market Price:

    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V0479
    CAS #: 862507-23-1 Purity ≥98%

    Description: Ralimetinib dimysylate (also known as LY-2228820; LY2228820) is a novel, potent and selective ATP-competitive inhibitor of p38 MAPK with IC50 of 7 nM in a cell-free assay, it does not alter p38 MAPK activation. In cell-based assays, LY2228820 potently and selectively inhibited phosphorylation of MK2 (Thr334) in anisomycin-stimulated HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse RAW264.7 macrophages (IC(50) = 35.3 nmol/L) with no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc ≤ 10 μmol/L. 

    References: Bioorg Med Chem Lett. 2008 Jan 1;18(1):179-83; Br J Haematol. 2008 May;141(5):598-606.

    Related CAS: 862505-00-8 (free base)

    Customer Validation
    Official Supplier of
    • VE
    • OF
    • YALE
    • hhmi
    • 香港大学
    Related Products
    Publications Citing InvivoChem Products
    • Citation of InvivoChem venetoclax and S63845
    • Citation of InvivoChem KD025 (SLx-2119)
    • Citation of InvivoChem Tubastatin A HCl
    • Citation of InvivoChem Paclitaxel
    • Citation of InvivoChem Colchicine
    • Citation of InvivoChem CA-170
    • Physicochemical and Storage Information
    • Protocol
    • Quality Control Documentation
    • Related Biological Data
    • Customer Review

    =

    Molecular Weight (MW)612.74
    FormulaC24H29FN6.2CH4O3S
    CAS No.862507-23-1
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 4 mg/mL warmed (6.5 mM)
    Water: 100 mg/mL (163.2 mM)
    Ethanol: 3 mg/mL (4.9 mM)
    Solubility (In vivo)Saline: 30 mg/mL
    Synonyms

    Ralimetinib; LY2228820; LY-2228820; LY 2228820; LY2228820 dimesylate

    Chemical Name: 5-(2-(tert-butyl)-5-(4-fluorophenyl)-1H-imidazol-4-yl)-3-neopentyl-3H-imidazo[4,5-b]pyridin-2-amine

    InChi Key: XPPBBJCBDOEXDN-UHFFFAOYSA-N

    InChi Code: InChI=1S/C24H29FN6/c1-23(2,3)13-31-20-17(28-22(31)26)12-11-16(27-20)19-18(14-7-9-15(25)10-8-14)29-21(30-19)24(4,5)6/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30)

    SMILES Code: NC1=NC2=CC=C(C3=C(C4=CC=C(F)C=C4)NC(C(C)(C)C)=N3)N=C2N1CC(C)(C)C 



    • Molarity Calculator
    • Dilution Calculator
    • The molarity calculator equation

      Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

      • Mass
      • Concentration
      • Volume
      • Molecular Weight *
      • =
      • ×
      • ×
    • The dilution calculator equation

      Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

      This equation is commonly abbreviated as: C1V1 = C2V2

      • Concentration (start)
      • ×
      • Volume (start)
      • =
      • Concentration (final)
      • ×
      • Volume (final)
      • ×
      • =
      • ×
      • C1
      •  
      • V1
      •  
      • C2
      •  
      • V2
    In Vitro

    In vitro activity: 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. 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.


    Kinase Assay: 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.


    Cell Assay: 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.

    In VivoIn 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.
    Animal modelLipopolysaccharide (LPS)-induced Balb/c mice
    Formulation & DosageDissolved in 1% CMC/0.25% Tween 80 in water;  0–20 mg/kg; Administered via p.o.
    References

    Bioorg Med Chem Lett. 2008 Jan 1;18(1):179-83; Br J Haematol. 2008 May;141(5):598-606.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    LY2228820

    LY2228820


    评论

      Home Prev Next Last page / pices

      发评论

      ×
      Your information is safe with us. * Required Fields.
      Products are for research use only;  We do not sell to patients
      Tel: 1-708-310-1919
      Fax: 1-708-557-7486
      Email: sales@invivochem.com
      Subscribe to our E-newsletter
      • Name*
      • *
      • E-mail*
      • *
      • instructions:
      • *
      Copyright 2020 InvivoChem LLC | All Rights Reserved