Platinum(II) <i>N</i> -heterocyclic carbene complexes arrest metastatic tumor growth
Pui‐Ki Wan, Ka‐Chung Tong, Chun‐Nam Lok, Chunlei Zhang, Xiaoyong Chang, Kong‐Hung Sze, Alice S.T. Wong, Chi‐Ming Che
Abstract
-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 µM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)‒NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers.