The subsets of
approximately 30,000 genes in the human genome that can bind to drug like
molecules by expressing proteins are called as “The Druggable Genome”. This concept is raised because of the
limitation of molecular targets for which commercially viable compounds can be
developed. This means that “The Druggable
Genome” which has the ability to produce proteins to bind
with drugs.
Commercially viable
drug means an orally bioavailable compound. Physico-chemical properties are
necessary to improve the oral bioavailability of drug which can be formalized
by the Lipinski “rule of five” analysis. Most successful drug achieves their
activity by searching for a binding site on protein with a small endogenous molecule.
It is necessary that a drug must bind to its target molecule with a reasonable
potency, to be more effective.
Survey has been taken
to find the molecular targets for a drug to bind on its binding site. Analysis
of International Drug Database and the
Pharmaprojects Database recognise
399 non-redundant molecular
targets. In that, several proteins are targeted by
experimental drugs and some are eliminated because of its inactivity according
to the rule of five analysis. Most of the drugs identified in this survey are
competitive. Those targets fall into the six gene families:
·
G-protein Coupled Receptors (GPCRs)
·
Serine/Threonine and Tyrosine protein
kinases
·
Zinc metallo-peptidases
·
Serine proteases
·
Nuclear hormone receptors
·
Phosphodiesterases
New methods such as
protein drugs, antibody
therapies, DNA vaccines and non-oral drug delivery systems,
could expand the range of potential targets those which can’t be identified by
rule of five analyses. The limited number of molecular targets for the drug
suggest that the druggable genome to be produced in a cost-effective manner.
This will be the major innovation for the pharmaceutical industry, not just in
the case of science, but also in the case of business.
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