Searching for individual active compounds in OxBC
The promise and the nature of the biological activity shown by OxBC raised the question as to the molecular origin(s) of the activity within the mixture of oxidation products. A chemical separation scheme was devised, which focused upon ultimately isolating, identifying and testing low molecular weight compounds that would be amenable to small-molecule drug development. Fractions and single compounds were screened in a battery of antiproliferative (i.e., inhibition of cell division) and differentiation cell culture-based assays and in a mouse mammary antitumour assay. Subsequently, individual bioactive compounds were identified and isolated from OxBC. In particular, a very low molecular weight compound (OCL-1) was identified as a particularly promising candidate compound and was subsequently synthesized by independent means.
Anticancer Activity
In standard animal and cell-culture tests, OCL-1 has been shown to inhibit the growth of a broad range of tumour cell types, including colon, breast, lung, brain, neuroblastoma, ovary and leukemia. Furthermore, the compound shows promise for inhibiting the spread of cancer cells, i.e., metastasis. Of fundamental importance, tumour inhibition in animals is achieved in all cases without any sign of toxicity. Also, the compound shows promising chemopreventive anticancer activity at low concentrations.
OCL-1 is Chemaphors' primary cancer drug candidate for the following reasons:
• Non-toxic inhibition of growth in mice of tumours derived from human cell lines
• Wide therapeutic range of activity
• Available orally
• Rapid tissue distribution and penetration predicted by low molecular weight (<150 Da) and fat-soluble nature
• Antimetastatic activity
• Chemopreventive anticancer activity
• Novel - although a carotenoid oxidation product, it is virtually an unknown compound
• No known reports of biological activity of any kind prior to Chemaphor's studies
• Unusual chemical structure with potential to elaborate into a distinct chemical class with a spectrum of biological activities
• Non-classical, non-toxic mechanism of anti-tumour action, e.g. enhanced gap junction intercellular communication
• Low manufacturing cost based on simplicity of chemical structure.
Cancer Tumour Management – The Urgent Need For New Drugs
In Canada and the US cancer is the second leading cause of death, after heart disease, accounting for one in every four deaths. Canada and the US represent roughly half of the global cancer drug market with four major cancers, lung, breast, prostate and colon, together accounting for more than half of all cancer deaths. The individual markets for the major cancers are estimated to be roughly $1-3 billion each.
Why OCL-1?
OCL-1 is an excellent candidate compound for development as a lead cancer drug, showing a broad range of anticancer activity in in vitro and in vivo assays. First, it is active against representatives of at least three of the four major cancers (colon, lung, breast; prostate remains to be tested), and others (brain, ovary, skin and some leukemias). Very importantly, the activity against mouse tumours grown in mice is entirely without any overt sign of toxicity. Second, our studies indicate OCL-1 is expected to have a broad spectrum of activity, ranging from prevention of cancer through to treatment of tumours and, in the most advanced cases, inhibiting cancer spread via metastasis. Using simple chemicals and as few steps as possible, we have developed an economical synthesis of the compound suitable for industrial scale-up.
OCL-1 has a wide spectrum of activity with respect to
cancer cell type and stage of cancer progression
The promise of
OCL-1 is threefold:
1. As a standalone drug and as a lead component of a drug
treatment combination for growth control and management of
various cancerous tumours
2. As a cancer chemopreventive, also most likely as part of
a drug treatment combination
3. Other disease application of restoring gap junctional
intercellular communication.