EntreMed preclinical compounds prevent tumor growth

Results of the studies demonstrated a potent, dose-dependent inhibition of tumor growth following the administration of the compound ENMD-1420 in two distinct preclinical models of metastatic lung and colorectal carcinoma. At maximally tolerated doses, tumor growth inhibition ranged from 80-90%.

Part of the mechanism by which ENMD-1420 exerted an antitumor effect involved the inhibition of angiogenesis, in addition to its antiproliferative activity. In vivo angiogenesis assays showed that the administration of ENMD-1420 at maximally tolerated doses led to the disruption of established blood vessels. Previous studies showed that ENMD-1420 inhibits tubulin polymerization and TNF-alpha production, contributing to its antiproliferative activity through apoptosis.

Carolyn Sidor, EntreMed vice president, stated: “These compounds have proven to be potent inhibitors of tumor growth and have both antiproliferative and antiangiogenic activities. We continue to evaluate ENMD-1420 and related compounds with the goal of identifying a lead molecule within the next twelve months.”

These compounds bind to tubulin protein and prevent cancer cell proliferation by interfering with the microtubule dynamics required for cell division. This interference blocks the cell cycle sequence, leading to cell death. ENMD-1420 and multiple compounds of a similar class are licensed from Celgene Corporation.