University of Pittsburgh

Bennett Van Houten

Wei Qian

Peter Wipf

Chaemin Lim

Compounds are provided that are useful in treating cancer and neurodegeneration. The compounds comprise a &#x3b2;-lapachone or &#x3b2;-lapachone derivative tricyclic ortho-naphthoguinone moiety linked to a mitochondria-targeting moiety, for example as defined with respect to Formula (I): or a pharmaceutically-acceptable salt thereof. Pharmaceutical compositions are provided comprising the composition. Methods of treatment of cancer and neurodegenerative disorders also are provided.

Substituted &#x3b2;-lapachones for treating cancer

The present invention relates to compositions and methods for reducing cell proliferation and/or promoting cell death. It is based, at least in part, on the discovery that in platinum drug-resistant cell lines, certain compounds, together with a second antiproliferative agent (e.g., cisplatin), act synergistically to promote apoptosis. Accordingly, the present invention provides for novel anticancer strategies.

Combination therapy to enhance the anticancer efficacy of platinum drugs

Provided herein are compounds having the general formula compositions, and methods useful for treating cancer and neurodegeneration. The compounds comprise a mitochondria-targeting moiety linked to &#x3b2;-lapachone or a &#x3b2;-lapachone derivative.

The present invention relates to compositions and methods for reducing cell proliferation and/or promoting cell death by inhibiting Drp1. It is based, at least in part, on the discoveries that (i) Drp1 disruption-induced mitochondrial hyperfusion is functionally linked to the cell cycle regulation apparatus, so that Drp1 inhibition results in a disruption of the cell cycle and DNA aberrancies; (ii) inhibition of both Drp1 and ATR are synthetic lethal causing increased DNA damage and apoptotic cell death; and (iii) even in resistant cell lines, Drp1 inhibitor (e.g., mdivi-1) together with a second antiproliferative agent (e.g., cisplatin or carboplatin) act synergistically to promote apoptosis. Accordingly, the present invention provides for novel anticancer strategies.

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Pittsburgh, PA, United States of America

Bennett Van Houten