Friday, March 20, 2009

The rule 2-0

Recently Aronov from Vertex pharmaceuticals proposed (JMC, 2008, 51,1214) a general ‘rule of thumb’ termed the 2-0 rule of kinase likeness to discriminating kinase compound from general compound .

For kinase activity the molecule should have

1) One or more hetero aromatic nitrogen’s
2) One or more hetero aromatic NH group
3) It contain one or more aniline
4) And it contain one or more nitriles



78 % of the kinase compound pass the 2-0 rule.

Saturday, March 14, 2009

Are Protein Kinase Drug Targets ?

20 –25% of druggable genome consists of kinase and this target account 20-30% of the drug discovery program of many companies.


Chem Med Chem 2007, 2,1116

Kinase inhibitors in the market include Tykerb® , Sprycel®, Sutent®,Nexavar®, Tarceva®, Iressa®, and of course Gleevec®.
D&MD Report 2005 shows that, Kinase targeted therapies 12.7bn 2005 to 58.6bn 2010, The key word search for kinase inhibitors 1281 patent filed in 2007 alone.



So what is the problem with kinase? Staurosporine that hits almost every kinase out there is going to be undoubtedly gratuitously toxic, Is "lake of selectivity" is the problem?
The real problem with kinase inhibitors is that toxic outcome may be the result of tissue distribution of orally administered kinase inhibitors.

The Answer is Yes! but,difficult one..