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Abstract

Abstract: DESCRIPTION: (Applicant's Description) ProIX Pharmaceuticals, Inc. has demonstrated that thioredoxin has an important role in maintaining the transformed phenotype of some human cancers as well as their resistance to chemotherapeutic drugs and thioredoxin is, a highly rational target for novel cancer drug development. The studies described herein suggest that a human anti-apoptosis oncogene that is overexpressed by a number of human cancers. ProIX Pharmaceuticals Inc. has the exclusive worldwide rights to develop the thioredoxin target and is dedicated to exploiting these observations and rapidly developing agents that selectively disrupt this novel signal transduction pathway. The objective of our initial Phase I proposal was to develop novel inhibitors of thioredoxin redox system based on a new class of selective inhibitors we had identified. Our Phase I studies have provided a promising clinical candidate, PX-12, as well as second and third generation agents. The objective of this Phase II proposal is to move our novel inhibitor of thioredoxin redox system, PX-12, through more extensive preclinical development and into a Phase I clinical trial. Secondary to this, we intend to continue the preclinical development of the second and third generation thioredoxin inhibitors. The Specific Aims of the proposal are as follows: 1) to complete Preclinical Evaluation of PX-12 including toxicologic, pharmaceutic and pharmacokinetic evaluation; 2) to complete GMP manufacture and formulation of PX-12; 3) to initiate a Phase I clinical trail of PX-12; 4) to conclude preclinical evaluation of second generation drugs, and to carry out parallel preclinical evaluation on novel third generation water soluble derivatives. ProIX Pharmaceuticals will have the exclusive world-wide license to develop these compounds as novel inhibitors of redox regulation and as potential anticancer agents by patents obtained from founding members of the company. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

Thesaurus Terms:
antineoplastic, drug design /synthesis /production, drug screening /evaluation, imidazole, inhibitor /antagonist, neoplasm /cancer pharmacology, sulfide, thioredoxin
breast neoplasm, clinical trial phase I, colon neoplasm, disulfide bond, dosage, gene expression, kidney neoplasm, leukemia, oncogene, pharmacokinetics
cell line, clinical research, dog, human subject, laboratory rat, neoplastic cell

Institution:	PROLX PHARMACEUTICALS, LP
	1401 FORBES AVE, STE 231
	PITTSBURGH, PA 15219
Fiscal Year:	2002
Department:
Project Start:	30-SEP-1997
Project End:	31-MAY-2003
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZCA1