T-1101 tosylate (TAI-95 tosylate) is a Hec1/Nek2 (Highly expressed in cancer 1 / NIMA-related kinase 2) inhibitor with antitumor activity. T-1101 tosylate is inactive toward normal cells, kinases and hERGIC50 & Target: Hec1/Nek2In Vitro: T-1101 tosylate shows potent in vitro antiproliferative activity (IC50: 14.8-21.5 nM).
T-1101 tosylate disrupts the Hec1/Nek2 protein–protein interaction in the cells.
T-1101 tosylate (1μM; 3-24 24 hours) decreases the level of Nek2 in a time-dependent manner.
T-1101 tosylate (1 μM; 24 hours) induces apoptosis.
T-1101 tosylate reduces amounts of cell-cycle related proteins cyclin A1, cyclin B1, and cyclin D1.
In Vivo: T-1101 tosylate shows good oral bioavailability and thermal stability .
Oral co-administration of T-1101 tosylate (2.5 mg/kg; p.o.; twice per day) halves the dose of sorafenib (25 mg/kg to 12.5 mg/kg) required to exhibit comparable in vivo activity towards Huh-7 xenografts .
T-1101 tosylate (2.5 mg/kg; p.o.; twice per day) shows significant in vivo activity in mice bearing various human cancer xenografts.