全国医药经济信息发布会-新药研发中和结构优化策略.ppt

Del-1 (E746-A750) and Del-2 (L747-T751) occur right after catalytic K745 and before helix C. This deletion will certainly interfere the salt bridge between K745 and E762 by either shifting the helix C position or changing the helix turn. Also in those deletions, the newly formed structure in this region has the potential to make contact with P-loop, and therefore change the P-loop conformation, (P-loop is a Gly rich loop and has extremely high mobility, and F723 in the P-loop make flip when the loop shifts and make new hydrophobic interactions. Inhibitor Lys 突变部位 EGFR Mutation Increase Iressa