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Abstract

Abstract: DESCRIPTION (provided by applicant): 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 APPLICATION: The annual anticipated revenues for an effective therapeutic to safely enhance radiation therapy is over $100 million in the US alone.

Thesaurus Terms:
drug design /synthesis /production, enzyme inhibitor, neoplasm /cancer radiation therapy, pentosyltransferase, radiosensitizer
DNA repair, apoptosis, drug screening /evaluation, water solubility
cell line, laboratory mouse

Institution:	INOTEK PHARMACEUTICALS CORPORATION
	100 CUMMINGS CTR, STE 419E
	BEVERLY, MA 01915
Fiscal Year:	2002
Department:
Project Start:	18-JUL-2001
Project End:	31-JUL-2003
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZCA1