Abstract

Triphenylphosphonium analogs of the MET kinase inhibitor PHA 665752 : An approach to the targeting of mitochondrial MET in lung cancer cell lines

Mei Lin Go, Associate Professor, National University of Singapore

There is evidence to implicate the translocation of MET kinase from the plasma membrane to the mitochondria of cancer cells. The triphenylphosphonium (TPP) moiety is widely acknowledged as a mitochondrial targeting warhead. We hypothesized that MET kinase inhibitors that are tagged to TPP would be preferentially directed to mitochondria of cancer cells. This would result in disruption of mitochondrial functions resulting in cell death. Here, the design and synthesis of a TPP -conjugated MET kinase inhibitor PHA 665752 is described and their comparative effects on isogenic lung cancer cells with normal / overexpression of MET kinase levels are presented.