ChemicalBook Product Catalog Biochemical Engineering Inhibitors Mitogen-activated protein kinase (MAPK) p38 MAPK inhibitor LY2228820

LY2228820

Product NameLY2228820
CAS862507-23-1
MFC26H37FN6O6S2
MW612.7369832
EINECS
MOL File862507-23-1.mol

Chemical Properties

storage temp.	Store at -20°C
solubility	≥30.65 mg/mL in DMSO; ≥45 mg/mL in H2O with ultrasonic; ≥9.9 mg/mL in EtOH with ultrasonic
form	solid
color	White to yellow
InChIKey	CQTHGFJRTIZYQG-UHFFFAOYSA-N
SMILES	C12N(CC(C)(C)C)C(N)=NC1=CC=C(C1NC(C(C)(C)C)=NC=1C1=CC=C(F)C=C1)N=2.CS(O)(=O)=O

Safety Information

HS Code

2933998090

Usage And Synthesis

Uses

LY2228820 is a novel and potent p38MAPK inhibitor with potent antiinflammatory activity. LY2228820 significantly inhibited phosphorylation of MAPKAPK2 and/or HSP27, down stream targets of p38MAPK, in both multiple myeloma (MM) cell lines and LT-BMSCs. LY2228820 is a potential candidate to improve MM patient outcome both by enhancing the effect of Bortezomib (B675700) and by reducing osteoskeletal events.

Biological Activity

ly2228820 is a potent, selective, atp-competitive small-molecule inhibitor inhibiting α- and β-isoforms of p38 mapk with ic(50) values of 5.3nm and 3.2 nm, respectively1.in multiple myeloma (mm) cell lines, ly2228820 enhanced the cytotoxicity of bortezomiba via reducing bortezomib-induced phosphorylation of heat shock protein 27 (hsp27). ly2228820 significantly reduced il-6 secretion from bm mononuclear cells (bmmncs) and long term cultured-bm stromal cells (lt-bmscs). besides, ly2228820 can also inhibit secretion of macrophage inflammatory protein-1a (mip-1a) in bmmncs, cd138+ patient mm cells and normal cd14+ osteoclast cells 2.studies in mice implanted with b16-f10 melanoma showed that orally administered ly2228820 can effectively suppress the tumor-phospho-mk2 expression. treatment of ly2228820 caused a significant tumor growth delay in a549 nsclc xenograft models1.

in vivo

In LPS-induced mice, Ralimetinib dimesylate 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), Ralimetinib dimesylate 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]. Ralimetinib dimesylate inhibits tumor phospho-MK2 in a dose-dependent manner (TED₅₀=1.95 mg/kg, TED₇₀=11.17 mg/kg) in mice implanted with B16-F10 melanoma. Ralimetinib dimesylate inhibits MK2 phosphorylation: mouse in vivo TED₅₀=1.01 mg/kg (compound exposure approximately 100 nM) and human ex vivo IC₅₀=0.12 μM with either mouse or human PBMC^[3].

target

p38α

IC 50

p38β MAPK: 3.2 nM (IC₅₀); p38α MAPK: 5.3 nM (IC₅₀)

References

1. campbell rm1, anderson bd, brooks na, brooks hb, chan em, de dios a, gilmour r, graff jr, jambrina e, mader m, mccann d, na s, parsons sh, pratt se, shih c, stancato lf, starling jj, tate c, velasco ja, wang y, ye xs.characterization of ly2228820 dimesylate, a potent and selective inhibitor of p38 mapk with antitumor activity. mol cancer ther. 2014 feb;13(2):364-74.2. ishitsuka k1, hideshima t, neri p, vallet s, shiraishi n, okawa y, shen z, raje n, kiziltepe t, ocio em, chauhan d, tassone p, munshi n, campbell rm, dios ad, shih c, starling jj, tamura k, anderson kc. p38 mitogen-activated protein kinase inhibitor ly2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications. br j haematol. 2008 may;141(5):598-606.

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