Crinobulin is a novel small molecule vascular disruption agent and apoptosis inducer for the treatment of patients with advanced solid tumors. Crinobulin has shown promising vascular targeting activity with potent anti-tumor activity in pre-clinical in vitro and in vivo studies. The molecule has been shown to induce tumor cell apoptosis and selectively inhibit growth of proliferating cell lines, including multi-drug resistant cell lines. Murine models of human tumor xenografts demonstrated Crinobulin inhibits growth of established tumors of a number of different cancer types. Two manuscripts on this compound were published in the November 2004 issue of Molecular Cancer Therapeutics.

Pre-clinical studies suggest that the anti-tumor effects of Crinobulin may be the result of a dual mechanism, a direct effect on disruption of tumor vascular endothelial cells leading to hypoxia and central tumor necrosis, as observed with vascular disruption agents, and a second effect on tumor apoptosis.

Stage of Development

In Q1 2009, EpiCept announced that it had completed the first study in man for Crinobulin.  EpiCept identified the maximum tolerated dose of Crinobulin in the Phase I study after 1 hour and 4 hour infusion. Crinobulin was administered as a single agent in increasing doses to small cohorts of patients with advanced solid tumors. A total of 33 patients were enrolled in the study. EpiCept intends to initiate a Phase 1B combination trial for the compound with other chemotherapeutic agents in 2009.