EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics primarily for the treatment of cancer and inflammatory diseases, has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute to evaluate the role of HIF-1á inhibition in the treatment of cancer.
Under the terms of the three-year agreement, the NCI’s Developmental Therapeutics Program Screening Technologies Branch (DTP-STB) and EntreMed will combine expertise and resources to investigate the mechanism of action by which EntreMed’s lead compound, 2-methoxyestradiol (2ME2) and a second generation analog of 2ME2, ENMD-1198, inhibits tumour hypoxia factor-1 alpha (HIF- 1á) in human cell lines. Additionally, animal tumour models will be used to establish the relationship between levels of 2ME2 in blood or tumour tissue and the inhibition of tumour growth.
The Tumour Hypoxia Laboratory within the NCI-DTP-STB has developed significant expertise in defining the role of HIF-1á inhibition in the development of novel anticancer and antiangiogenic agents. This expertise will help to further clarify and define the antiangiogenic and anti-tumour properties of 2ME2 and its analog, ENMD-1198.
It has been demonstrated in preclinical studies that 2ME2 is a potent inhibitor of HIF-1á, and its down-regulation is closely associated with 2ME2’s tubulin inhibitor properties. HIF-1á is over expressed in more than 70% of human tumours and HIF-1á over-expression correlates with tumour aggressiveness, metastases and poor prognosis. 2ME2 attacks tumours on multiple fronts – directly by disrupting microtubules, an intracellular matrix necessary for the rapid division of cancer cells (mitosis), by inducing programmed cell death (apoptosis), and by blocking blood vessels that feed tumours (angiogenesis inhibition).
Carolyn F. Sidor, EntreMed vice president and chief medical officer, commented on the CRADA, “We are pleased to have the opportunity to work with the National Cancer Institute and their team of experts in the field of tumour hypoxia. We believe that 2ME2 has the potential to be a unique cancer therapy by attacking tumours that are dependent on the pro-angiogenic activity of HIF-1á. The NCI collaboration will provide EntreMed with access to well-established in vitro and in vivo models of HIF-1á inhibition.”
EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation.