I was always under the impression that it was Prof Kelly's work mostly, that lead to some of the lead candidates that MEIP now has , not so , it was Dr Andrew Heaton that was responsible for the design
and execution that gave rise to the lead compounds ME128, ME196, ME143, and ME344, he was also the instigator in forming the company Triaxial, so we get the person who founded Novogen initially, with it's drug Phenoxodiol and we also get the person who went on to develop that platform into these other compounds, what do they have install for us now with this new drug CS6 for the treatment of Brain Cancer it is part of the family called Super Zopyrans, so MEI got what we once had but we still get to keep a lot more for NRT it seems, we still have another few shots in the locker, no wonder the US is excited.
I hope these new drugs developed by Triaxial will just be extensions of the existing compounds that MEI have? for it may mean less testing in the long run?
Novogen’s New Technology Explained
December 5, 2012
Our first post is an attempt to explain a key part of Novogen’s newly-acquired technology. This is the so-called ‘Stealth’ technology……. created specifically to improve the chances of our drugs reaching their cancer target in a fully active state.
First, a bit of terminology that we need to clear up. You might be used to hearing Novogen’s anti-cancer drugs being referred to as isoflavonoids. That is a chemical term. It simply means a particular molecular shape with hydrogen, oxygen and carbon atoms in the appropriate places. All the drugs that Novogen was working on some years ago were all variations of the basic isoflavone molecular scaffold.
The drugs that Novogen is working on now still have an isoflavone heritage, but are so much more complex than the Company was able to produce before that they have become an entirely new family of chemical compounds, only distantly related to isoflavonoids. We refer to these as super benzopyrans.
But the one bit of critical heritage that super benzopyran molecules such as CS-6 have and which is shared by simple isoflavonoid anti-cancer drugs is a particular shape of the head of the molecule that is crucial to binding to the cancer cell target. Where they differ is in the shape of the tail of the molecule, that part of the molecule that delivers the anti-cancer action.
A good analogy is to imagine the molecule as a scorpion….two claws up-front grabbing hold of the prey and a tail then delivering the killer blow. The two ‘claws’ of the isoflavone molecule is how the molecule binds to a particular protein either externally on the cancer cell’s outer membrane or internally on its mitochondrial membrane, with the tail of the molecule then blocking certain functions within the cancer cell leading to its death or malfunction.
The isoflavone ‘claws’ are in fact terminal hydroxyl (OH) groups that are highly chemical reactive. That high reactivity ensures that once they get to a cancer cell they will home in on the target and attach firmly. The problem, however, is that this high chemical reactivity also means that they are prone to binding to a range of substances before they get to the cancer cell. And in this form the isoflavone is inactive…unable to bind to the cancer cell. To use our scorpion analogy again, it would be like putting boxing gloves on the scorpion’s claws, making it impossible for it to grab its prey.
Virtually all isoflavone drug injected into the blood of a patient ends up being bound in this way. The process is called conjugation, with the two main reactive substances being a sugar (glucuronide) or a salt (sulfate). Conjugated isoflavones have no anti-cancer activity and rely on the presence of specific enzymes in the end tissue to cleave off the sugar or the salt in order to release the active isoflavone drug. Normal, healthy tissues are well served with the necessary enzymes to undertake this cleaving; cancer tissues, on the other hand, less so. It’s a lottery….some cancer tissues contain the necessary enzymes, whereas others (probably the majority) don’t, or at best, don’t contain much.
Enter Triaxial’s Stealth technology. We have developed a technology that allows the creation of super benzopyran structures in which the fundamental isoflavone cancer binding site (scorpion claws) is retained, but the tail has been expanded to the point that its anti-cancer potency is considerably enhanced. We have increased the potency of the scorpion’s sting. But in creating the super benzopyran structure, it also emerged that we substantially reduced the susceptibility of the molecule to conjugation. CS-6 is a prime example of this …. a molecule with an exceptionally potent anti-cancer sting in its tail, but two claws that in the laboratory, anyway, are showing a much reduced susceptibility to conjugation.
That’s the promise of this technology. We now proceed to the job of testing this promise in pre-clinical studies