KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.

Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that specifically inhibit the KRAS isoform by binding to an allosteric site encompassing the region around KRAS-specific residue histidine 95 at the helix α3/loop 7/helix α4 interface. We show that these DARPins specifically inhibit KRAS/effector interactions and the dependent downstream signalling pathways in cancer cells. Binding by the DARPins at that region influences KRAS/effector interactions in different ways, including KRAS nucleotide exchange and inhibiting KRAS dimerization at the plasma membrane. These results highlight the importance of targeting the α3/loop 7/α4 interface, a previously untargeted site in RAS, for specifically inhibiting KRAS function

Review of the Economy 2010/11

The Economic Advisory Council in its review of the economy has predicted a continued high growth but has suggested steps to sustain this growth, chief among them:Containing inflation by focusing both on monetary and fiscal policies and supply side management; the pace of infrastructure creation has to be stepped up with renewed focus on the power sector; continue efforts to contain Current Account Deficit (CAD) at 2-2.5 per cent of GDP and in parallel encourage flow of external investments into the country; and greater attention to agriculture including on seed development, management of water and soil fertility and improving delivery http://eac.gov.in/reports/revieweconomic_201011.pdfgrowth, inflation, power, agriculture, infrastructure