LY2228820

Ralimetinib dimesylate (LY2228820) is a selective, ATP-competitive inhibitor of p38 MAPK α/β with IC50s of 5.3 and 3.2 nM, respectively.

Ralimetinib Mesylate is the dimesylate salt form of LY2228820, a tri-substituted imidazole derivative and orally available, p38 mitogen-activated protein kinase (MAPK) inhibitor with potential anti-inflammatory and antineoplastic activities. Upon administration, ralimetinib inhibits the activity of p38, particularly the alpha and beta isoforms, thereby inhibiting MAPKAPK2 phosphorylation and preventing p38 MAPK-mediated signaling. This may inhibit the production of a variety of cytokines involved in inflammation, cellular proliferation and angiogenesis such as tumor necrosis factor alpha (TNFa), interleukin (IL)-1, -6 and -8, vascular endothelial growth factor, and macrophage inflammatory protein-1 alpha. Ultimately this induces apoptosis and reduces tumor cell proliferation. In addition, inhibition of the p38 MAPK pathway by LY2228820 increases the antineoplastic activity of certain chemotherapeutic agents. p38 MAPK, a serine/threonine protein kinase that is often upregulated in cancer cells, plays a crucial role in tumor cell proliferation, angiogenesis and metastasis.

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.

Molecular Weight:612.7
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:11
Rotatable Bond Count:5
Exact Mass:612.22000343
Monoisotopic Mass:612.22000343
Topological Polar Surface Area:211
Heavy Atom Count:41
Complexity:701
Covalently-Bonded Unit Count:3
Compound Is Canonicalized:Yes