| 摘要 |
Described are mitochondria-targeted anti-tumor agents, and methods of making and using the same for the treatment of disorders associated with unwanted cell proliferation. The present invention is based, at least in part, on the discovery that the molecular chaperones Hsp90, Hsp60, and TRAP-I are found at increased levels in mitochondria of tumor cells as compared to normal cells, and that inhibition of molecular chaperones in tumor cell mitochondria ?sing mitochondrial-targeted chaperone inhibitors results in tumor cell death. In one aspect, the invention provides compositions having the formula: A-B, wherein A is a molecular chaperone inhibitor and B is a mitochondria-penetrating moiety and A and B are linked, optionally by a linking moiety; or a pharmaceutically acceptable salf thereof. However, if A is Shepherdin or a fragment thereof, then B is not Antennapedia helik Ui homeodomain cell-penetrating peptide (ANT) or a fragment thereof. |
