Pui-Ki Wan,Ka-Chung Tong,Chun-Nam Lok,Chunlei Zhang,Xiao-Yong Chang,Kong-Hung Sze,Alice Sze Tsai Wong,Chi-Ming Che
Metastasis is a common cause of cancer mortality yet a daunting challenge in oncology. We have discovered a cytotoxic platinum(II) N -heterocyclic carbene complex that not only suppressed primary tumor growth in mice but also impeded metastatic growth of breast cancer and melanoma with long-term tolerance attributable to its eventual biotransformation into less-toxic, excretable products. It directly engages the cytoskeletal protein vimentin that plays pivotal roles in cancer stemness, survival, and invasion. It binds vimentin noncovalently via the distinct structural scaffold with a dissociation constant of 1 μM as determined by surface plasmon resonance, NMR, and molecular dynamics simulations, revealing the significance of harnessing noncovalent interactions of metal compounds with important molecular targets in the development of new anticancer metal medicines.
X-ray crystallographic data have been deposited in The Cambridge Crystallographic Data Centre,
(accession nos. , , and ). All study data are included in the article and/or [ SI Appendix ].