(18th Oct 2005) MerLion Pharmaceuticals announces collaborative research agreement with the National Cancer Institute.
MerLion Pharmaceuticals Pte Ltd, a Singapore-based drug discovery company today announced the establishment of a research collaboration with the National Cancer Institute (NCI) of the USA.
The overall goal of this agreement is the discovery and development of novel small molecule inhibitors of the hypoxic signaling pathway from MerLion’s proprietary library of natural products. Under the agreement with the Screening Technologies Branch (STB) of the NCI MerLion has been granted access to assays and cell lines developed at in the laboratories of Dr Robert Shoemaker and Dr. Giovanni Melillo for the molecular marker, Hypoxia Inducible Factor-1 α (HIF-1α), which is over-expressed in many human cancers.
HIF-1α over-expression in biopsies of brain, breast, cervical, esophageal, oropharyngeal and ovarian cancers is correlated with resistance to chemotherapy, radiotherapy and mortality. In addition, over-expression is associated with increased vascularity and tumor progression and has been observed in more than 70% of human cancers and their metastases including bladder, breast, colon, glial, hepatocellular, ovarian, pancreatic, prostate, lung, renal and head and neck cancers
“We are delighted to have entered into this agreement with the Screening Technologies Branch of NCI”, said Dr Tony Buss, CEO of MerLion. “Naturally produced compounds often inhibit specific protein-protein interactions which may be of particular importance in this modulation of HIF-1 expression. The prospect of screening for inhibitors of this pathway against such a diverse set of natural product chemistry offers a unique opportunity of identifying genuinely novel, active chemistry in this target area”
Under this Cooperative Research and Development Agreement (CRADA), MerLion will perform initial screening and identification of candidate molecules. Both parties may then further investigate and develop these drug candidates for use in potential clinical investigations.
The NCI-STB has a long and well-documented track record in lead discovery from natural products as well as small molecule chemical libraries. More recently the STB has developed a number of cell-based high throughput assays used to identify small molecule inhibitors of molecular targets relevant to cancer growth and angiogenesis.
“This agreement with the NCI is in keeping MerLion’s goal, which is to partner with premier academic groups and pharmaceutical companies worldwide, and to identify candidate molecules against validated drug targets” said Dr. Buss.
MerLion Pharma works in partnership with large pharmaceutical and biotech companies worldwide. The company’s current partners include Abbott Laboratories, Arpida SA, Astellas Pharma Inc, Cancer Research Technologies, Dow AgroSciences, the Institute of Molecular and Cell Biology (Singapore), Johns-Hopkins (USA), KuDOS Pharmaceuticals, Merck and Co, NovImmmune SA, Nura Inc, Sankyo Co Ltd and Schering-Plough Inc.
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Notes for editors:
Hypoxia Inducible Factor-1 (HIF-1) is a protein composed of two subunits, HIF-1α and HIF-1β. HIF-1 mediates tumor cell responses to changes in oxygen concentration and belongs to a class of molecules termed transcription factors. As such, a transcription factor recognizes and binds to specific regions of DNA. In the case of HIF-1, binding results in the activation of >60 genes encoding for proteins involved in cell proliferation and survival, angiogenesis, energy metabolism e.g. glucose transporters and glycolytic enzymes and invasion and metastasis. HIF-1 represents a mechanism whereby tumor cells can react to stress and continue to survive. These survival, migration and invasion factors are particularly relevant for cancer progression. HIF-1 is thus recognized as an attractive target for development of novel cancer therapeutics.
HIF-1 can only turn on genes when both protein subunits, HIF-1α and HIF-1β come together. The HIF-1α subunit, in contrast to HIF-1β, is highly regulated within the cell, being formed in response to growth factor stimulation or when oxygen levels drop. Under normal oxygen conditions, the levels of HIF-1α and therefore HIF-1 transcription activity, are absent or low. When oxygen concentrations are low (hypoxia), the levels of HIF-1α are high and HIF-1 transcription activity is initiated. In addition to increased HIF-1α expression in tumor lesions as a result of hypoxia, genetic mutations can also lead to active levels of HIF-1α These genetic mutations include both gain-of-function mutations in oncogenes as well as loss-of-function in tumor suppressor genes. As a result of hypoxia and genetic mutations, HIF-1α protein is therefore over-expressed in many human cancers