KX2-361 (KX-02) is a Src-kinase and tubulin polymerization inhibitor. KX2-361 shows good oral bioavailability and readily crosses the BBB in mice. KX2-361 shows anti-tumor activity and induces apoptosis of Glioblastoma (GBM) cell.
KX2-361 (0-200 nM, 24-72 h) reduces autophosphorylation of Src in GL261 cells[1].KX2-361 (0-270 nM) promotes cell cycle arrest at the G2/M phase in U87 cells. Note the dose dependent effect and virtual complete arrest at 270 nM[1]. KX2-361 (0-800 nM) induces apoptosis of U87, GL261 and T98G cell lines[1].KX2-361 (5 µM) inhibits the in vitro assembly of tubulin polymers[1].
KX2‑361 significantly delays progression of orthotopic GL261 brain tumors and produces long‑term survival[1].KX2-361 demonstrates appreciable brain penetration when dosed orally to mice (20 mg/kg), with a brain Cmax of 4025±319 ng/g observed 15 min post-dosing and an overall exposure (AUClast) of 5044±355 h ng/g[1].
References:
[1]. Ciesielski MJ, et al. KX2-361: a novel orally bioavailable small molecule dual Src/tubulin inhibitor that provides long term survival in a murine model of glioblastoma. J Neurooncol. 2018 Dec;140(3):519-527.