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Abnormal expression or mutations in Rasproteins has been found in upto 30% of cancer cell types, making them excellent protein models to probestructure-function relationships of cell-signaling processes that mediate celltransformtion. Yet, there has been very little development of therapies to helptackle Ras-related diseased states. The development of small molecules totarget Ras proteins to potentially inhibit abnormal Ras-stimulated cellsignaling has been conceptualized and some progress has been made over the last 16 or so years. Here, we briefly review studiescharacterizing Ras protein-small molecule interactions to show the importanceand potential that these small molecules may have for Ras-related drug discovery.We summarize recent results, highlighting small molecules that can bedirectly targeted to Ras using Structure-Based Drug Design SBDD andFragment-Based Lead Discovery FBLD methods. The inactivation of Ras oncogenicsignaling in vitro by small moleculesis currently an attractive hurdle to try to and leap over in order to attack the oncogenic state. In thisregard, important features of previously characterized properties of small molecule Ras targets, as well as a currentunderstanding of conformational and dynamics changes seen for Ras-related mutants,relative to wild type, must be taken into account as newer small moleculedesign strategies towards Ras are developed.


Ras Rat Sarcoma; Small Molecule Target; Structure-Based Drug Design; Fragment-Based Drug Design; GTP Hydrolysis; Guanine Nucleotide Exchange Factors GEF

Cite this paper

Chandrashekar, R. and Adams, P. 2013 Prospective Development of Small Molecule Targets to Oncogenic Ras Proteins. Open Journal of Biophysics, 3, 207-211. doi: 10.4236-ojbiphy.2013.34025.

Autor: Reena Chandrashekar, Paul D. Adams



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