Ralimetinib (LY2228820)

Catalog No.S1494

Ralimetinib (LY2228820) Chemical Structure

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.

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5 Customer Reviews

  • 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.

    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.

  • 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.

    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.

  • 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.

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.
Targets
p38α [1]
(Cell-free assay)
7 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
RPMI-8226 MWnLbY5ie2ViYYPzZZk> MnHZglgxOCCwTR?= NFLKR|RFVVOR M4nlVolvcGmkaYTzJJBpd3OyaH;yfYxifGmxbjDv[kBJW1B{Nx?= MlnHNVg{QTd|NEW=
U266 M37Wc2tqdmG|ZTDhd5NigQ>? MXL+PFAxKG6P M2ft[GROW09? MYfpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? M3HLPFE5Ozl5M{S1
MM.1S NH;5XVNMcW6jc3WgZZN{[Xl? MVz+PFAxKG6P NXnUZXJ[TE2VTx?= Mn3ubY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGhUWDJ5 NGrGbnQyQDN7N{O0OS=>
RPMI-Dox40 NWHnTFk2U2mwYYPlJIF{e2G7 M{\VUZ45ODBibl2= MX3EUXNQ NYrPZm9FcW6qaXLpeJMheGixc4Doc5J6dGG2aX;uJI9nKEiVUEK3 NGjq[YEyQDN7N{O0OS=>
RPMI-LR5 NIDqZmFMcW6jc3WgZZN{[Xl? MUf+PFAxKG6P MV7EUXNQ NE\PNpBqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhUFOSMke= M1XkflE5Ozl5M{S1
INA-6 MVrLbY5ie2ViYYPzZZk> MWL+PFAxKG6P MUTEUXNQ MXvpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? M2fYVlE5Ozl5M{S1
RPMI-8226 NFrKOphEgXSxeHnjbZR6KGG|c3H5 M4jK[Z4yODByIH7N MXXEUXNQ M{HLXY5wKHOrZ37p[olk[W62IHP5eI91d3irY3n0fS=> MnrRNVg{QTd|NEW=
U266 NXLlbmhWS3m2b4jpZ4l1gSCjc4PhfS=> NHL4Rot,OTByMDDuUS=> MVzEUXNQ NVXONnF5dm9ic3nncolncWOjboSgZ5l1d3SxeHnjbZR6 NIfmfVgyQDN7N{O0OS=>
MM.1S M2rUcWN6fG:6aXPpeJkh[XO|YYm= MWP+NVAxOCCwTR?= MW\EUXNQ MnTYco8he2mpbnnmbYNidnRiY4n0c5RwgGmlaYT5 MnLCNVg{QTd|NEW=
RPMI-Dox40 MorKR5l1d3irY3n0fUBie3OjeR?= MUP+NVAxOCCwTR?= M1PhOGROW09? M2POeY5wKHOrZ37p[olk[W62IHP5eI91d3irY3n0fS=> MXSxPFM6PzN2NR?=
RPMI-LR5 NUPQfmlpS3m2b4jpZ4l1gSCjc4PhfS=> M3Xsd54yODByIH7N Mk\2SG1UVw>? M3O2UY5wKHOrZ37p[olk[W62IHP5eI91d3irY3n0fS=> NIe3[|cyQDN7N{O0OS=>
INA-6 M17tWGN6fG:6aXPpeJkh[XO|YYm= MX;+NVAxOCCwTR?= NHPEOmlFVVOR NIG5c49vdyC|aXfubYZq[2GwdDDjfZRwfG:6aXPpeJk> Ml7GNVg{QTd|NEW=
CD14+ MV\GeY5kfGmxbjDhd5NigQ>? NYGzRmxQhjhyMDDuUS=> NWnVNFEzTE2VTx?= M1PrWYlvcGmkaYTzJI9{fGWxY3zhd5Rw\2WwZYPpd{Bnem:vIFPENVQheG:|aYTpeoUh[2WubIO= MkDrNVg{QTd|NEW=
U-87-MG M2PxNWZ2dmO2aX;uJIF{e2G7 M1O5d|Eh|ryP M1PIRWROW09? MkHSdoVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= MW[yN|M{PTVyNh?=
MDA-MB-231 MWHGeY5kfGmxbjDhd5NigQ>? NUnk[ZY1OSEQvF2= MWnEUXNQ M{HrZ5Jm\HWlZYOgeJVud3JvZILpeoVvKGOxcnSg[o9zdWG2aX;u NXrnXmJPOjN|M{W1NFY>
A-2780 M{jH[mZ2dmO2aX;uJIF{e2G7 NFnQSXQyKM7:TR?= Ml;oSG1UVw>? NVXPVllpemWmdXPld{B1fW2xcj3kdol3\W5iY3;y[EBnd3KvYYTpc44> MXeyN|M{PTVyNh?=
SK-OV-3 M2\Q[2Z2dmO2aX;uJIF{e2G7 NFrxW4UyKM7:TR?= MVXEUXNQ MXjy[YR2[2W|IIT1cY9zNWS{aY\lckBkd3KmIH\vdo1ifGmxbh?= NGXTSY0zOzN|NUWwOi=>
LXFA-629 MW\GeY5kfGmxbjDhd5NigQ>? NVXtPJpUOSEQvF2= M4WyPGROW09? MmKxdoVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= M3\veFI{OzN3NUC2
NCI-H1650 NHvnbpJHfW6ldHnvckBie3OjeR?= M4LIWlEh|ryP NX3jUmJuTE2VTx?= NVHzdohMemWmdXPld{B1fW2xcj3kdol3\W5iY3;y[EBnd3KvYYTpc44> NG\4R5YzOzN|NUWwOi=>
PC-3 M{LHeWZ2dmO2aX;uJIF{e2G7 NF\MVXgyKM7:TR?= NWnlV2NDTE2VTx?= NGi1TIFz\WS3Y3XzJJR2dW:{LXTybZZmdiClb4LkJIZwem2jdHnvci=> MXGyN|M{PTVyNh?=
RAW264.7 MXjGeY5kfGmxbjDhd5NigQ>? NXHscW1yhjJyIN88US=> MYHEUXNQ MXXpcohq[mm2czDBcol{d227Y3nuMZN1cW23bHH0[YQhVUt{IIDoc5NxcG:{eXzheIlwdiC5aYToJGlEPTBib3[gN|UvOyCwTR?= NVfPc2Y5OjR|NU[4NVQ>
mouse peritoneal macrophages Ml\pSpVv[3Srb36gZZN{[Xl? MoLEglIxKM7:TR?= M1TMbGROW09? M3PaXWxRWy:LRl6t{tPjiJO|dHnteYxifGWmIGTOSk3PuSCycn;keYN1cW:wIIfpeIghUUN3MDDv[kA3NjNibl2= NYPDW3hOOjR|NU[4NVQ>
A549 Ml7wSpVv[3Srb36gZZN{[Xl? M{HJTp4zOCEQvF2= Mm\wSG1UVw>? MYPpcohq[mm2czDMVHMucW6mdXPl[EBEYEOOODDwdo9lfWO2aX;uJJdqfGhiSVO1NEBw\iBzNESuPUBvVQ>? Mo[0NlQ{PTZ6MUS=
MDA-231 MlPRSpVv[3Srb36gZZN{[Xl? NHvkbpZ,OTBizszN M17UbJN2eHC{ZYPz[ZMhTEuNLUGg[ZhxemW|c3nvci=> M{TMfFI3PDB5OESz
MCF-7 NGqwTVVHfW6ldHnvckBie3OjeR?= MUT+NVAh|ryP MYTzeZBxemW|c3XzJGRMUy1zIHX4dJJme3Orb36= NIPBcoIzPjRyN{i0Ny=>
MDA-435 NEHpe25HfW6ldHnvckBie3OjeR?= NU\ae4tKhjFyIN88US=> M{C3c5N2eHC{ZYPz[ZMhTEuNLUGg[ZhxemW|c3nvci=> NEC0eo8zPjRyN{i0Ny=>
PC3 NVzDN5FmTnWwY4Tpc44h[XO|YYm= MlXVglExKM7:TR?= NV\0fXR{TE2VTx?= M2fYWZN2eHC{ZYPz[ZMhTEuNLUGg[ZhxemW|c3nvci=> NUfPdmo{OjZ7MUO2NFg>

... Click to View More Cell Line Experimental Data

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]
+ Expand

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.
Cell Research:[2, 3]
+ Expand
  • Cell lines: MM cells, including INA6, RPMI-8226, U266, and RPMI-Dox40
  • 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Lipopolysaccharide (LPS)-induced Balb/c mice
  • Formulation: Dissolved in 1% CMC/0.25% Tween 80 in water
  • Dosages: 0–20 mg/kg
  • Administration: Oral bid dosing for 14 days
    (Only for Reference)

Solubility (25°C)

In vitro Water 100 mg/mL warmed (163.2 mM)
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:
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

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02364206 Recruiting Adult Glioblastoma Centre Jean Perrin|National Cancer Institute, France|ARC Foundation for Cancer Research June 2015 Phase 1|Phase 2
NCT02322853 Recruiting Postmenopausal|Metastatic Breast Cancer Centre Francois Baclesse|National Cancer Institute, France|ARC Foundation for Cancer Research January 2015 Phase 2
NCT01663857 Active, not recruiting Epithelial Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Cancer Eli Lilly and Company July 2012 Phase 1|Phase 2
NCT01393990 Completed Advanced Cancer Eli Lilly and Company August 2008 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID