RAS GTPase AS THE DRUG TARGET FOR ANTI-CANCER DESIGNING OF DRUG FROM TEMPLATE
AbstractRas proteins in association with GTP and GDP act as a bio-molecular switch for signaling cell growth, cell survival and signal transduction. The presence of mutated Ras proteins is found to vary in different cancer types and the highest occurrence of about 90% is observed in pancreatic cancer. The Ras GTPase binding site is mainly involved in signal cell proliferation. Hence, this binding site has been considered as a major target. At the same time, targeting a specific protein and designing the drug molecule with respect to that is practically of no use as the target proteins are fast mutating. In this scenario, designing the template from the hot spot of proteins and fitting the template for all the target protein molecules seem to be a promising technique. The templates are initially screened on the basis of pharmacokinetic and pharmacodynamic requirements. Six templates are found to be satisfying conditions like IC50, lipophilic efficiency, ligand efficiency etc. and their efficiencies are compared with standard reference molecules. The computed enrichment factors support these templates to be leads for effective anti-cancer drugs subject to further in vitro and in vivo evaluation.
Article Information
48
4457-4461
399KB
1156
English
IJPSR
A.S. Krishnapriya and P.K. Krishnan Namboori*
Computational Chemistry Group, Amrita Molecular Modeling and Synthesis (AMMAS) Research Laboratory, Computational Engineering and Networking, AMRITA Vishwa Vidyapeetham, Amritanagar, Coimbatore-641 112, Tamil Nadu, India
n_krishnan@cb.amrita.edu
27 June, 2013
31 July, 2013
25 October, 2013
http://dx.doi.org/10.13040/IJPSR.0975-8232.4(11).4457-61
01 November, 2013
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