A novel functional approach toward identifying definitive drug targets.
The process of developing drugs dates to antiquity. The herbal formulations during the old days were more traditional than with any scientific rationale. As different branches of physics, chemistry and biology started revealing the physiological processes in molecular details and as the sophisticated methods for probing into these phenomena were innovated, the processes of drug development changed significantly. However, the very first step in the process which is defining a drug target remains a major hurdle. The classical methods that predate the functional genomics and proteomics involve a cumbersome, painstaking detailing of a given enzyme or a receptor, followed by its validation as a target. The sophisticated methods in the post-genomic and proteomic era reduced the time taken to define targets, but the speed of drug discovery is not necessarily as quick as it promised. This is primarily due to prolific predictions pressing validation too hard, although both non-robotic and robotic high throughput screenings match with the requirement. Since these drugs target pathogens, a serious disadvantage with these methodologies is the emergence of drug resistance. Therefore, we propose a functional approach whereby the host-pathogen interaction is studied to find out the alterations in immune responses, the profile of host gene expression and activation of cell signaling molecules, the kinases in particular. Such interactions often induce the expression of those genes and activation of those proteins which are required for their survival. We demonstrate that reversal of such profiles of gene expression and protein activation ameliorates the infection. Therefore, those gene products and the kinases with pro-parasitic functions can serve as targets.
Dey
Ranadhir
R
National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
Khan
Srijit
S
Saha
Bhaskar
B
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004351:Drug Resistance; D020536:Enzyme Activators / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D023281:Genomics / Q000379:methods; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D004364:Pharmaceutical Preparations; D040901:Proteomics / Q000379:methods; D034741:RNA, Small Interfering / Q000235:genetics
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D034741:RNA, Small Interfering