Anavex has developed seven cancer leading product candidates in four major cancer areas, (colon, prostate, breast and lung), in which there is a crucial need for innovative medicines.

The unique properties of sigma receptors turn sigma ligands to a class of novel promising drug candidates against cancer.

Sigma receptors of periphery tissues are found in endocrine, immune, and reproductive tissues and in high density in liver and kidney. Thus, it is likely that sigma receptors have important functions outside the nervous system and subserve a more general role than a neurotransmitter receptor.It has been shown that 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. In the human breast, sigma receptors were virtually absent in normal tissue but were present in high density in breast tumor biopsy tissue. Their high density in various tumor cell types, and particularly in proliferating cells, makes sigma receptors potential therapeutic agents. Anavex 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 and to exhibit similar potency in tumors with wild-type or mutant p53, 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.

ANAVEX, taking advantage of these unique drug-binding receptors, is now testing compounds, characterized as sigma-ligands, for their anticancer activity using state of the art technology. So far, more than twenty compounds have demonstrated significant activity (i.e. to inhibit the growth of cancer cells at low micromolar level concentrations), while a couple of them have demonstrated very high activity, inhibiting growth of the cells at the nanomolar level of concentrations. All these compounds are now extensively tested in vitro against the most common types of cancer that is leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney using the very same approach and criteria used for this purpose from NCI/NIH, USA. Additionally, compounds with unique novel chemical structures and significant in vitro activity (growth inhibition of cancer cells at concentrations <10μΜ) are further tested for their efficacy to inhibit tumor growth in in vivo models. Toxicity tests done so far, have demonstrated that the compounds are not harmful when administered in naive mice even at fairly high doses. Compounds selected for in vivo testing have being found in in vitro assays to activate apoptosis in cell lines and interfere with the phases of the cell cycle in a dose, time and structure dependent manner. Experiments are currently in progress to further study and unravel the apoptotic mechanism that is activated by those compounds. The compounds will be further studied in vivo as well as in vitro in a more extensive and detailed way, in an attempt to fully elucidate their activity against various cancers and to study their effects in critical aspects for the tumor and disease development, such as angiogenesis and metastasis.