Published Paper 1

This is my first published paper review (its gonna need some updating) and I have to admit, I had no idea of the complexity of enzymes and …my head hurts now so I shall not be going in depth to this article. Ofcourse you are free to read it on your own.

Have you ever heard of a Kinase Inhibitor Disease? I haven’t!

Firstly what is a kinase?

A kinase is an enzyme which “modifies” a molecule by means of transfer of a phosphate from an ATP molecule to the molecule which takes part in the catalysed reaction.

According to the abstact of the article, Kinases have important roles when it comes to signalling pathways and cell regulation….. So what does this mean for humans, kinases….kinase inhibitirs….cell regulation?

I’m not sure what you are thinking but I do believe if you have a kinase inhibitor, you are basically not going to have proper metabolic mechanisms and therefore you are pretty much dying slowly 😦

Ok that may have been a little harsh.

The article goes on to mention that diseases (cancers, neurological and metabolic) often characterize the ability to deregulate kinase functions and it is expected that these may be a particular target when dealing with drugs. Meaning inhibitors are good…when using them AGAINST the diseases. However problems arise:

They are large in numbers
The lack selectivity/ specificity
They tend to unintentionally interact with multiple protein kinases
They are unbiased and so would react with the kinases which belong to the body (these are what cause side effects from drugs)

Yi-Yuan Chiu and associates have created a database on a mass number of kinases and inhibitors in order to find which would have been useful. This database is referred to as KIDFamMap.

KIdFamMap is the first database to explore the relationship between kinase-inhibitor-families (KIF’s) andKinase-inhibitor-disease (KID) with reference to the selectivity between enzyme and inhibitor.

SOME OUTSIDE INFO:

“A protein kinase inhibitor is one in which specifally blocks activity of one or more protein kinases.” Most of the kinases known today act on both serine and thysorine. I.e. they have a dual specificity. Kinases cause the phosphorylation of their complementary amino acids and since they can also react with histidine, a kinase may possess the ability to alter, interfere or even repair DNA. The fact that a kinase can affect DNA makes its inhibitor useful in the treatment of cancer.

Here is a list of drugs I found which target kinase inhibitors:

Name	Target	Company	Class	FDA Approval
Bevacizumab	VEGF	Genentech	Monoclonalantibody	2004 Colorectal
BIBW 2992	EGFR/Erb2	Boehringer Ingelheim	Small molecule	Not yet
Cetuximab	Erb1	Imclone/BMS	Monoclonal antibody	2006 Mar (SCCHN)
Imatinib	Bcr-Abl	Novartis	Small molecule	2001 (CML)
Trastuzumab	Erb2	Genentech/Roche	Monoclonal antibody	1998
Gefitinib	EGFR	AstraZeneca	Small molecule	2003
Ranibizumab	VEGF	Genentech	Monoclonal antibody	2006 (AMD)
Pegaptanib	VEGF	OSI/Pfizer	RNA Aptamer	2004 (AMD)