K145 HCl

Description: K145 is a novel, potent and selective SphK2 (sphingosine kinase-2) inhibitor with an IC50 of 4.30+/-0.06 uM and without inhibition of SphK1 at concentrations up to 10 uM. As a selective sphingosine kinase-2 (SphK2) inhibitor, K145 has anticancer activity and inhibited the activity of SphK2 in a dose-dependent manner. Biochemical assay results indicate that K145 is a selective SphK2 inhibitor. Molecular modeling studies also support this notion. In vitro studies using human leukemia U937 cells demonstrated that K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of down-stream ERK and Akt signaling pathways. K145 also significantly inhibited the growth of U937 tumors in nude mice by both intraperitoneal and oral administration, thus demonstrating its in vivo efficacy as a potential lead anticancer agent. The antitumor activity of K145 was also confirmed in a syngeneic mouse model by implanting murine breast cancer JC cells in BALB/c mice. Collectively, these results strongly encourage further optimization of K145 as a novel lead compound for development of more potent and selective SphK2 inhibitors.

References: PLoS One. 2013; 8(2):e56471.

Related CAS #: 1449240-68-9 (HCl); 1309444-75-4 (free base)