TM608 is a novel, highly potent and selective c-MET inhibitor with anticancer activity, it targets Mitochondrial and Kills Erlotinib-Resistant Lung Cancer Cells. TM608 is the first TPP-TKI conjugate, can rapidly accumulates in mitochondria and suppresses the activation of MET in high MET expressing, erlotinib-resistant HCC827B cells (total cell lysates and mitochondrial fractions). TM608 was as potent and apoptogenic as PHA665752 in abrogating NSCLC cell viability. Directed accessibility to the mitochondria as afforded by a targeting moiety like TPP could conceivably compensate for deficient activity if uptake is rapid, cumulative, and selective.