INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin

Invest New Drugs. 2008 Feb;26(1):1-5. doi: 10.1007/s10637-007-9072-5. Epub 2007 Jul 13.


Poly(ADP-ribose) synthetase inhibitor, INO-1001, is known to sensitize cells to radiation in vitro by inhibiting the repair of DNA damage. Recent evidence has suggested that PARP inhibition may also be a way of selectively targeting p53 deficient cancer cells. The present study tested INO-1001 for its in vivo effect on the chemoresponse of two p53 deficient tumors, human breast cancer MDA-MB-231 and murine mammary carcinoma MCa-K. Doxorubicin was used as the DNA damaging agent and tumor growth delay assay was used as the endpoint. Results showed that INO-1001 was highly effective in enhancing the anti-tumor effects of Doxorubicin for both MDA-MB-231 (EF=1.88) and MCa-K (EF=1.64). We conclude that PARP inhibitor INO-1001 has high potential for enhancing the anti-tumor effects of chemotherapy agents such as Doxorubicin against p53 deficient breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control
  • Cell Line, Tumor
  • Doxorubicin / pharmacology*
  • Doxorubicin / therapeutic use
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / prevention & control*
  • Mice
  • Mice, Inbred C3H
  • Mice, Nude
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Tumor Burden / drug effects
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays*


  • Antibiotics, Antineoplastic
  • INO 1001
  • Indoles
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Tumor Suppressor Protein p53
  • Doxorubicin