talmapimod hydrochloride

Talmapimod hydrochloride is a selective and ATP-competitive p38α inhibitor (IC50: 9 nM). It also shows about 10-fold selectivity over p38β, and at least 2000-fold selectivity over a panel of 20 other kinases, including other MAPKs.

Talmapimod (SCIO-469) is a selective, orally active, ATP-competitive p38α inhibitor with IC50 values of 9 nM for p38α and 90 nM for p38β. Talmapimod exhibits at least 2000-fold selectivity over a panel of 20 kinases, including other MAPKs.

Selective, ATP-competitive p38 inhibitor (IC50 = 9 nM for p38α in vitro). Displays approximately 10-fold selectivity for p38α over p38β and 2000-fold selectivity for p38α over 20 other kinases. Reduces p38α phosphorylation in multiple myeloma cells in vitro and in vivo; activity results in decreased tumor burden and angiogenesis in murine models of multiple myeloma. Also enhances bortezomib-induced cytotoxicity against multiple myeloma cells. Hideshima et al (2004) p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells. Oncogene. 23 8766 PMID:15480425 |Giafis et al (2006) Role of the p38 mitogen-activated protein kinase pathway in the generation of arsenic trioxide-dependent cellular responses. Cancer Res. 66 6763 PMID:16818652 |Vanderkerken et al (2007) Inhibition of p38α mitogen-activated protein kinase prevents the development of osteolytic bone disease, reduces tumor burden, and increases survival in murine models of multiple myeloma. Cancer Res. 67 4572 PMID:17495322