Inhibition Of Dynamin Related Protein 1 To Promote Cell Death

Abstract

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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Document History
  • Publication: Jun 24, 2014
  • Application: Apr 18, 2012
    US US 201213450345 A
  • Priority: Apr 18, 2012
    US US 201213450345 A
  • Priority: Apr 19, 2011
    US US 201161476759 P

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