Replies to post #97682 on Innovation Pharmaceuticals Inc (IPIX)

[rr50]

SLC - Thanks again for your research. When I see a post by you I automatically click on it to gain additional in-depth info relating to our products. The process is so automatic & easy that I forget to state my appreciation for what you provide for this board. We all benefit through your research & observational comments. Keep it coming!

[frrol]

SLC: Old post from OrionNebula on MDMX and Kevetrin. Kevetrin isn't an MDMx down-regulator, that's not its MOA.

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=93253954

[To infinity and beyond!]

calling kmbjn, or whatever the letters are.

the PNAS paper is an attempt to better characterize the interaction of MDMX with p53. MDMX is an inhibitor of p53. They are saying that protein fragments that mimic parts of p53 will block this inhibition.

So, as you can see, I cannot understand it not very far, after reading it several times....

[farrell90]

Biochemical geniuses can design proteins and other agents based on the 3D structure of the molecule. Determining the structure can be an important step in drug design and development.

https://www.cs.princeton.edu/courses/archive/fall05/cos597A/lectures/design.pdf

Good luck Farrell

[KMBJN]

I agree with what others have said about this paper. One, that regulation of proteins and pathways in the cell is very complex, and two, that this paper just talks about the conformational states of the complex MDMX protein - how it can fold in different shapes that then either inhibit or activate (remove inhibition) p53.

An attempt at a simple? re-telling:

MDMX is another molecule (like MDM2) that inhibits p53 activity.
Normally, MDMX inhibits p53 when the p53-similar part of MDMX binds to the p53 binding pocket (the part of MDMX that binds to p53 and inhibits it), actually causing a change in the shape of MDMX to better enable it to bind to and inhibit p53.

MDMX inhibition of p53 is turned off (i.e. p53 is activated) when DNA damage causes CK1a to disrupt MDMX from sticking to itself (the p53 mimic portion no longer binds to the p53 binding pocket), thus hiding the p53 binding pocket so it no longer interacts with p53. So, when DNA is damaged, MDMX changes from its normal shape, inhibits p53 less, p53 is activated, and the DNA damage is dealt with.

I suppose this would be another way to activate p53 besides kevetrin MOA and besides the MDM2 inhibitors (which make p53 more stable and slow to be broken down). If one can mimic CK1a or otherwise alter MDMX so it no longer inhibits p53, this is an additional route of p53 activation. The authors also claim this paper validates their protein fragment release (PFR) method of studying how different portions of a large protein interact with the other portions.