IC50: 3.14 μM for glioma cells

Vacquinol-1 is a MAPK kinase 4 (MKK4) activator.

Mitogen-activated protein kinase (MAPK) is a type of protein kinase that is specific to the amino acids serine, threonine, and tyrosine. MAPKs regulate cell functions such asgene expression, mitosis, proliferation, differentiation, cell survival, as well as apoptosis.

In vitro: Previous study showed that vacquinol-1 displayed high cytotoxicity against glioma cells, resulting in a complete loss of viability as measured by ATP depletion. Vacquinol-1 could selectively target GCs in mixed cocultures with human fibroblasts. Moreover, vacquinol-1 had no effect on caspase activity at any concentration or time point, which was unlike that of staurosporin. In addition, the fluorescence staining and western blot analyses of GCs for activating MKK4 phosphorylation revealed a rapid and pronounced activation by vacquinol-1 at 7.5 μM [1].

In vivo: The ability of vacquinol-1 to attenuate tumor progression was previously tested in a mouse model for human GBM. Vacquinol-1 or vehicle (DMSO) were intracranially administered into the site of original cell deposit 6 weeks after engraftment. Results showed that tumors were invariantly smaller, and the area of necrosis and hGFAP and hNestin immunoreactivity was significantly reduced. Moreove, only tumor cells in vacquinol-1-treated mice showed a massive LAMP1 staining [1].

Clinical trial: Up to now, vacquinol-1 is still in the preclinical development stage.

Reference:
[1] Kitambi SS et al.  Vulnerability of glioblastoma cells to catastrophic vacuolization and death induced by a small molecule. Cell. 2014 Apr 10;157(2):313-28.