Design and synthesis of phosphate based Inositol & Mannose: Potential ras inhibitors

Rat sarcoma virus, RAS, the name originated from the Sarcoma viruses developed during the extensive study of transforming retrovirus isolated from Rat, mice, cats, monkeys and responsible for the highly oncogene properties of RNA tumor viruses. It is the family of GTPase (HRAS, NRAS, and KRAS) protein kinase that are highly conserved in humans and its plays critical role in basic cellular functions such as apoptosis, cell proliferation, cell growth and differentiation. It has G domain consist of 170 amino acids having weight about 20KDa, which binds guanosine nucleotides. RAS genes constitutes the most frequently mutated oncogene family in human cancer, mutation in RAS is found in 20% to 30% of all human tumors and up to 90% in some specific cancers such as pancreatic cancer. Therefore it is necessary to explore small molecule inhibitors that could hamper GDP binding to stop mutant RAS activity which in turn inhibit certain types of cancer. It is very challenging job to make GDP competitive inhibitor as compared to the ATP competitive because it has more energy and strong binding affinity in comparison with ATP. It would be highly appreciable if we synthesize those molecules which selectively inhibit the RAS pathway. Considering these facts our preliminary aim is to synthesize few derivatives of pyrophosphate Inositol and mannose as RAS inhibitor, also designing the novel inhibitor for RAS based on molecular docking studies.