Ralimetinib dimesylate

For research use only.

Catalog No.S1494 Synonyms: LY2228820 dimesylate

50 publications

Ralimetinib dimesylate Chemical Structure

CAS No. 862507-23-1

Ralimetinib (LY2228820) dimesylate 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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Selleck's Ralimetinib dimesylate has been cited by 50 publications

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Description Ralimetinib (LY2228820) dimesylate 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 NIHEXWdMcW6jc3WgZZN{[Xl? MWD+PFAxKG6P M3fVPGROW09? NGfSV2lqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhUFOSMke= M2e2blE5Ozl5M{S1
U266 MULLbY5ie2ViYYPzZZk> MoD1glgxOCCwTR?= MXLEUXNQ M3PLXIlvcGmkaYTzJJBpd3OyaH;yfYxifGmxbjDv[kBJW1B{Nx?= MlL0NVg{QTd|NEW=
MM.1S NW[2PXlrU2mwYYPlJIF{e2G7 MWH+PFAxKG6P NEHRU5VFVVOR MWHpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? MYWxPFM6PzN2NR?=
RPMI-Dox40 NUHuSVlzU2mwYYPlJIF{e2G7 NFHL[mZ,QDByIH7N NFj5eFlFVVOR MUXpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? MXqxPFM6PzN2NR?=
RPMI-LR5 MlfoT4lv[XOnIHHzd4F6 NFyzW5Z,QDByIH7N MVHEUXNQ M13ORYlvcGmkaYTzJJBpd3OyaH;yfYxifGmxbjDv[kBJW1B{Nx?= M3nzZlE5Ozl5M{S1
INA-6 MkLET4lv[XOnIHHzd4F6 NUn3NXhyhjhyMDDuUS=> MYDEUXNQ MlXGbY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGhUWDJ5 MYOxPFM6PzN2NR?=
RPMI-8226 MV3DfZRwgGmlaYT5JIF{e2G7 M{fGdJ4yODByIH7N MVzEUXNQ NYP0eHM{dm9ic3nncolncWOjboSgZ5l1d3SxeHnjbZR6 M3HBWlE5Ozl5M{S1
U266 NI[ySGZEgXSxeHnjbZR6KGG|c3H5 M3PxNJ4yODByIH7N MkT1SG1UVw>? MWXuc{B{cWewaX\pZ4FvfCCleYTveI95cWOrdIm= MmrjNVg{QTd|NEW=
MM.1S NILFXnFEgXSxeHnjbZR6KGG|c3H5 NIDk[mt,OTByMDDuUS=> NITqTVRFVVOR NFv3cmhvdyC|aXfubYZq[2GwdDDjfZRwfG:6aXPpeJk> NWXTcFlzOTh|OUezOFU>
RPMI-Dox40 MWrDfZRwgGmlaYT5JIF{e2G7 M{SxUJ4yODByIH7N M3TnW2ROW09? MnHIco8he2mpbnnmbYNidnRiY4n0c5RwgGmlaYT5 MUSxPFM6PzN2NR?=
RPMI-LR5 MkC2R5l1d3irY3n0fUBie3OjeR?= NFLxdG9,OTByMDDuUS=> NEm0dFNFVVOR NHXrRXFvdyC|aXfubYZq[2GwdDDjfZRwfG:6aXPpeJk> M2P2RVE5Ozl5M{S1
INA-6 NX;rcpk5S3m2b4jpZ4l1gSCjc4PhfS=> MUP+NVAxOCCwTR?= MmntSG1UVw>? M1HmW45wKHOrZ37p[olk[W62IHP5eI91d3irY3n0fS=> Mo\5NVg{QTd|NEW=
CD14+ NGLzOVFHfW6ldHnvckBie3OjeR?= M4Xre545ODBibl2= MnHJSG1UVw>? NFvxN2NqdmirYnn0d{Bwe3Snb3PsZZN1d2enbnXzbZMh\nKxbTDDSFE1KHCxc3n0bZZmKGOnbHzz M{K0N|E5Ozl5M{S1
U-87-MG NIr5SJdHfW6ldHnvckBie3OjeR?= MXmxJO69VQ>? M13VdmROW09? MoD6doVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= NGDG[ZIzOzN|NUWwOi=>
MDA-MB-231 NX;Xb|VyTnWwY4Tpc44h[XO|YYm= MoPoNUDPxE1? M2T4dGROW09? MljTdoVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= NX2wZ2E1OjN|M{W1NFY>
A-2780 NVrlc3pVTnWwY4Tpc44h[XO|YYm= Mm\JNUDPxE1? NHjMbFlFVVOR M2rhS5Jm\HWlZYOgeJVud3JvZILpeoVvKGOxcnSg[o9zdWG2aX;u MoKzNlM{OzV3ME[=
SK-OV-3 M37UXGZ2dmO2aX;uJIF{e2G7 MX6xJO69VQ>? MljnSG1UVw>? NGXBXINz\WS3Y3XzJJR2dW:{LXTybZZmdiClb4LkJIZwem2jdHnvci=> NXHmNFVYOjN|M{W1NFY>
LXFA-629 NVn2eZJ7TnWwY4Tpc44h[XO|YYm= M363ZVEh|ryP M1\0bmROW09? M3HTe5Jm\HWlZYOgeJVud3JvZILpeoVvKGOxcnSg[o9zdWG2aX;u NGTSdFIzOzN|NUWwOi=>
NCI-H1650 NF7ZVmhHfW6ldHnvckBie3OjeR?= NFu4[GIyKM7:TR?= MUXEUXNQ MULy[YR2[2W|IIT1cY9zNWS{aY\lckBkd3KmIH\vdo1ifGmxbh?= NXXrUoJCOjN|M{W1NFY>
PC-3 MmnXSpVv[3Srb36gZZN{[Xl? NXXDfG5{OSEQvF2= NXzaWoRMTE2VTx?= MYfy[YR2[2W|IIT1cY9zNWS{aY\lckBkd3KmIH\vdo1ifGmxbh?= M{LoNVI{OzN3NUC2
RAW264.7 NXzQN3h3TnWwY4Tpc44h[XO|YYm= NXG4[oNQhjJyIN88US=> MULEUXNQ MYPpcohq[mm2czDBcol{d227Y3nuMZN1cW23bHH0[YQhVUt{IIDoc5NxcG:{eXzheIlwdiC5aYToJGlEPTBib3[gN|UvOyCwTR?= NGW2d|AzPDN3NkixOC=>
mouse peritoneal macrophages MVPGeY5kfGmxbjDhd5NigQ>? MoDhglIxKM7:TR?= NX3lfFdQTE2VTx?= MlzlUHBUN0mITj5Ot-KBm3O2aX31cIF1\WRiVF7GMe6yKHC{b3T1Z5Rqd25id3n0bEBKSzVyIH;mJFYvOyCwTR?= NYPFeIYyOjR|NU[4NVQ>
A549 M3nE[WZ2dmO2aX;uJIF{e2G7 M3\GT54zOCEQvF2= M2LzOWROW09? NUPF[pA2cW6qaXLpeJMhVFCVLXnu[JVk\WRiQ2jDUFgheHKxZIXjeIlwdiC5aYToJGlEPTBib3[gNVQ1Njlibl2= MXKyOFM2PjhzNB?=
MDA-231 M3\o[WZ2dmO2aX;uJIF{e2G7 M{DzWZ4yOCEQvF2= MWTzeZBxemW|c3XzJGRMUy1zIHX4dJJme3Orb36= MWqyOlQxPzh2Mx?=
MCF-7 NH33NFdHfW6ldHnvckBie3OjeR?= MUX+NVAh|ryP M3LDNJN2eHC{ZYPz[ZMhTEuNLUGg[ZhxemW|c3nvci=> MUWyOlQxPzh2Mx?=
MDA-435 MXLGeY5kfGmxbjDhd5NigQ>? M{m0[Z4yOCEQvF2= NHTaZld{fXCycnXzd4V{KESNSz2xJIV5eHKnc4Ppc44> MXuyOlQxPzh2Mx?=
PC3 NGjqVW5HfW6ldHnvckBie3OjeR?= NX\ITY55hjFyIN88US=> NIDEOZJFVVOR M1\ydpN2eHC{ZYPz[ZMhTEuNLUGg[ZhxemW|c3nvci=> M3zT[lI3QTF|NkC4

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-p38 / p38α / p38β / p-MK2 / MK2 / p-HSP27 / HSP27; 

PubMed: 23335506     


whole cell protein extracts were isolated from ECFCs or ADSCs following pretreatment with DMSO (−) or 1 μm LY2228820 dimesylate (+) for 30 min prior to the addition of 10 ng/ml VEGF, bFGF, EGF, or 100 ng/ml IL-6, and then the extracts were subjected to Western blot analysis using antisera directed against p-p38, p38α, p38β, p-MK2, total MK2, p-HSP27, total HSP27, and β-actin as a loading control.

p-S6K ; 

PubMed: 26844273     


CRC cells were treated with 4 μM LY2228820, 10 μM BIRB796 or 10 μM SB202190 for 2 h and p38 and mTORC1 signaling was analyzed by immunoblot.

23335506 26844273
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.
Cell Research:[2, 3]
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  • 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]
- Collapse
  • Animal Models: Lipopolysaccharide (LPS)-induced Balb/c mice
  • 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(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 LY2228820 dimesylate
Smiles CC(C)(C)CN1C2=C(C=CC(=N2)C3=C(N=C(N3)C(C)(C)C)C4=CC=C(C=C4)F)N=C1N.CS(=O)(=O)O.CS(=O)(=O)O

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID