talmapimod-hcl

Description: Talmapimod, formerly known as SCIO-469, is a novel, orally bioavailable, and selective p38 mitogen-activated protein kinase (MAPK) inhibitor with an IC50 of 9 nM and has potential immunomodulating, anti-inflammatory, and antineoplastic activities. It shows about 10-fold selectivity over p38beta, andat least 2000-fold selectivity over a panel of 20 other kinases, including other MAPKs. Talmapimod specifically binds to and inhibits the phosphorylation of p38 MAPK, which may result in the induction of tumor cell apoptosis, the inhibition of tumor cell proliferation, and the inhibition of tumor angiogenesis. This agent may also enhance proteasome inhibitor-induced apoptosis.

References:

1. HideshimaT et al. p38 MAPK inhibition enhances PS-341 (bortezomib)-inducedcytotoxicity against multiple myeloma cells. Oncogene. 2004 Nov 18, 23(54), 8766-76.

2. NavasT, et al. Inhibition of p38alpha MAPK disrupts the pathological loop ofproinflammatory factor production in the myelodysplastic syndrome bonemarrow microenvironment. Leuk Lymphoma. 2008 Oct; 49(10):1963-75.

3. VanderkerkenK et al. Inhibition of p38alpha mitogen-activated protein kinaseprevents the development of osteolytic bone disease, reduces tumorburden, and increases survival in murine models of multiple myeloma.Cancer Res. 2007 May 15; 67(10):4572-7.

4. MedicherlaS, et al. p38alpha-selective MAP kinase inhibitor reduces tumor growthin mouse xenograft models of multiple myeloma. Anticancer Res. 2008Nov-Dec; 28(6A):3827-33.