New cancer drug target discovered: HDAC3-IP4

[Techne]

New cancer drug target discovered

Scientists at the University of Leicester have identified a new molecule that could serve as a target for an entire family of future cancer drugs.

Future cancer drugs may work by targeting the interaction between DNA (orange) and histones (blue)​

Cancer research has been booming in the last decade with an estimated global annual spend of over €14,000 million (£11,600 million). While more than 800 drugs are currently in development, a failure rate of 95%[1] means that new target molecules are always welcome.

Future cancer drugs may work by targeting the interaction between DNA (orange) and histones (blue)
Cancer can be caused by over-expression of growth-promoting genes (oncogenes) or under-expression of growth-suppressors (tumour suppressors). Genes are not always readily available for transcription into messenger RNA molecules – their accessibility is tightly controlled by DNA packaging mechanisms.

Within the nucleus, DNA is tightly wrapped around molecules called histones. Histone tails largely carry positive charge due to amine groups on the lysine and arginine amino acids. These positive charges interact with the negatively charged phosphate groups on the sugar-phosphate backbone of DNA. Eight histone molecules form a core around which DNA is wrapped to form a nucleosome, and several nucleosomes are needed to package a single strand of DNA.

Adding acetyl groups, ‘acetylation’, neutralises positive charges, weakening the DNA-histone interactions. This allows parts of the DNA to unwind and become more accessible to transcription enzymes. Histone deacetylases are enzymes that remove these acetyl groups, returning the DNA to its tightly packed structure. They therefore silence or supress the expression of genes.

A team lead by Prof. John Schwabe[2] recently discovered a surprising link between histone deacetylases and the inositol phosphate signalling pathway. They showed that IP4 (inositol 1,3,4,5 – tetrakisphosphate) molecules regulate histone deacetylases, and hence the gene silencing mechanism.

Prof. Schwabe suggests that new drugs that manipulate this interaction, for example by regulating IP4 production within the body, or by inhibiting IP4 interactions with histone deacetylases, may have potential as novel anti-cancer agents.

Written by Architha Srinivasan

[1] http://www.discoverymedicine.com/Jennifer-Arrondeau/2010/10/26/development-of-anti-cancer-drugs/

[2] http://www2.le.ac.uk/news/blog/2012...ries-of-gene-expression-can-help-treat-cancer

I thought this was quite interesting. After reading some of the comments in this thread about "evil-Big-Pharma", this is a good opportunity to stick it to those "evil overlords" by designing your own drugs using freely available software.

Here is how:
1) Here is the peer-reviewed article.
2) Here is the actual structure of the protein:

3) Notice that in the center of the picture there is a binding pocket for the IP4 molecule which plays an activation role in the activity of HDAC3. The aim is to find or design compounds that can bind to that pocket and thus prevent its HDAC3 activity.

It's not rocket science. There is good, freely available software out there that can be used.
E.g.
1) Chimera and MGLTools for molecule editing.
2) Autodock and Autodock Vina for fast and efficient docking of compounds into proteins to see how they potentially bind.
3) The ZINC database for a library of ligands to test. Or you can design your own 3D molecules here.

I am sure the IT boffins and science enthusiasts here at MyBB can get it going. I can help.

Have fun .

 

[RiaX]

lol yeah thats not going to happen

 

[Techne]

Why not?

 

[RiaX]

Its one thing being a boffin and its another pretending you a boffin with huge amounts of reading.

Plus I assume people surfing @ work will have that stuff blocked and in your free time it be more entertaining playing xbox or something

 

[Techne]

Like I said, it's not rocket science and anybody that is interested can do it with a little guidance.