Anavex Life Sciences Corp. today announced that ANAVEX 7-1037 has been shown to kill human HCT116 colon cancer cells in advanced pre-clinical studies. In addition, ANAVEX 7-1037 demonstrated its ability to significantly suppress tumor growth in immune-deficient mice. ANAVEX 7-1037 is the company's lead drug candidate for the treatment of colorectal cancer and other types of solid tumors.
"These results are very encouraging, particularly regarding the therapeutic signals from the significant in vivo anti-cancer activity against HCT116 xenografts at low nanomolar level," said Dr. Kontzalis, Chief Executive Officer for ANAVEX. "We are committed to further exploring the benefits of ANAVEX 7-1073 as we aim to develop first-class therapeutics to fight various types of cancer."
A novel small synthetic sigma ligand, ANAVEX 7-1037 is a member of a new class of drugs designed to treat colorectal and other types of human cancer. Toxicological studies in mice have shown no evidence of the side effects that are usually observed with anti-cancer drugs available today. In pre-clinical lab tests, ANAVEX 7-1037 has demonstrated its ability to kill cancer cells.
Preclinical testing of ANAVEX 7-1037 also reveals that the drug candidate:
- exhibits high affinity for sigma-1 (nanomolar) and moderate (micromolar) affinity for sigma-2 and sodium channels;
- induces initially detachment of cells as early as 6 hours after the addition of 20 micromolars to the culture and subsequent apoptosis that was accompanied by activation of both caspases -8 and -9 and subsequent activation of caspase 3, as this was estimated by FACS and western blot analysis; and
- causes growth delay when administrated i.p. to SCID mice, suggesting a significant in vivo anticancer activity against HCT116 xenografts, according to NCI criteria.
As such, pre-clinical studies so far suggest that ANAVEX 7-1037 may possess chemotherapeutic potential for the treatment of colorectal and other types of human cancer.
Ongoing pre-clinical studies are being conducted in collaboration with Universite Montpellier in France. These studies on immune-deficient mice are designed to assess and analyze ANAVEX 7-1037's ability to slow down and prevent tumor growth, stop cancer cells from spreading, enable the growth of new blood vessels and increase the number of cells through cell growth and division.
Published results were presented at the 15th Euroconference on Apoptosis (Portoroz, Slovenia).
About Colorectal Cancer
Colorectal cancer is an extremely common form of cancer. It has the second highest mortality rate of all cancers in the western world. By 2010, it is predicted that over 480,000 people will be diagnosed with colorectal cancer in the seven major pharmaceutical markets (France, Germany, Italy, Spain, UK, USA and Japan), with a prevalent population of 1.6 million individuals.
Colorectal cancer originates in the epithelial cells, which line the gastrointestinal tract. Cancer of the colon occurs when there are abnormal cells that result in a tumor. Many of the abnormal cells first develop as polyps inside the colon or rectum and with time can become cancerous and spread to secondary sites. The major classes of cancer therapies available today include antineoplastics, immunostimulants, immunosuppressants and cytostatic hormone therapies. However, these currently available drugs are insufficient to treat the disease; instead, they have some effect in treating the symptoms and are accompanied by significant side effects.
Drugs that act on the underlying cause of the disease and/or slow/reverse the progression of the disease, which have a novel mode of action that could fulfill some of the most urgent medical needs like efficacy, drug resistance, side effects, administration and affordability, are needed and have blockbuster potential. ANAVEX is developing drug candidates demonstrating the above properties.
About Sigma Receptors
Sigma receptors are a unique family of proteins, present mainly in the central nervous system (CNS) but also in various peripheral tissues. The receptors are classified into two subtypes: the sigma-1 and sigma-2. These subtypes are distinguishable pharmacologically, functionally and by molecular size. Sigma-1 receptors have been cloned and shown to be distinct from any known receptor class.
Both sigma receptor subtypes are highly expressed in tumor cell lines from various tissues. These include neuroblastomas, glioma, melanoma and carcinoma cell lines of breast, prostate and lung. Interestingly, sigma receptors are more highly expressed in rapidly proliferating cells and are down-regulated when cells become inactive. Their high density in various tumor cell types, and particularly in proliferating cells, makes sigma receptors a potential target for diagnostic imaging as well as therapeutic agents. Recent data suggest that sigma-2 receptor agonists induce cell death in various tumor cell lines including prostate and breast carcinoma, with features consistent with apoptosis. Sigma-2 receptor agonists are reported to induce apoptosis by a novel mechanism, exhibiting similar potency in tumors with wild-type or mutant p53 gene, unlike other agents such as DNA-damaging agents. The mechanism of sigma-2 receptor-mediated apoptosis differs from that of agents that trigger DNA damage, based on observations with inhibitors of caspases. The involvement of distinct apoptotic pathways is further supported by the ability of sigma agonists to potentiate the cytotoxicity of DNA-damaging antineoplastics in various tumor cell lines.
Anavex Life Sciences Corp. is an emerging biopharmaceutical company engaged in the discovery and development of novel drug targets for the treatment of cancer and neurological diseases. The company's proprietary SIGMACEPTOR™ Discovery Platform involves the rational drug design of compounds that fulfill specific criteria based on unmet market needs and new scientific advances. Selected drug candidates demonstrate high, non-exclusive affinity for sigma receptors, which are involved in the modulation of multiple cellular biochemical signaling pathways.
ANAVEX's SIGMACEPTOR™ -N program involves the development of novel and original drug candidates, targeting neurological and neurodegenerative diseases (Alzheimer's disease, epilepsy, depression, etc.). The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for anti-amnesic, neuroprotective, anti-apoptotic, anti-oxidative, anti-inflammatory, anti-convulsive, anti-depressant and anxiolytic properties.
ANAVEX SIGMACEPTOR™ -C program involves the development of novel and original drug candidates targeting cancer. The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for selective pro-apoptotic, anti-metastatic and low toxicity properties in various types of solid cancers such as colon, prostate, breast, lung, etc.
CONTACT: Anavex Life Sciences Corp., Research & Business Development; Shareholder & Media Relations, Toll-free: 1-866-505-2895, Outside North America