Activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARP) has been implicated in the process of recovery from radiation induced cell injury. Consequently, inhibitors of PARP or cells deficient from PARP exhibit enhancements in their radiation sensitivity. The principle of this radiosensitizing effect of PARP inhibition can be exploited for the development of novel radiosensitizing agents for cancer therapy. The applicants are developing a series of novel, proprietary PARP inhibitors, with a high potency, good water-solubility and optimal cell penetration characteristics. The goal of the present application, supported by preliminary data, is to confirm that the applicants' proprietary, novel PARP inhibitors act as potent radiosensitizers in vivo, and to select a lead candidate for further preclinical development (i.e. toxicity and safety studies). The results of the present application will permit application for Phase 2 funding to support: completion of pre-clinical pharmaceutical testing (additional advanced toxicity determinations, pathology, stability, pharmacokinetics), preparation of investigational drug application to the FDA, and a Phase I and II clinical trials.

Proposed Commercial Applications

The annual anticipated revenues for an effective therapeutic to safely enhance radiation therapy is over $100 million in the US alone.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43CA090016-02
Application #
6498028
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (M1))
Program Officer
Stone, Helen B
Project Start
2001-07-18
Project End
2004-01-31
Budget Start
2002-08-01
Budget End
2004-01-31
Support Year
2
Fiscal Year
2002
Total Cost
$205,022
Indirect Cost
Name
Inotek Pharmaceuticals Corporation
Department
Type
DUNS #
City
Beverly
State
MA
Country
United States
Zip Code
01915
Brock, William A; Milas, Luka; Bergh, Sherry et al. (2004) Radiosensitization of human and rodent cell lines by INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase. Cancer Lett 205:155-60