Accession Number:

AD1024706

Title:

Clinical Development of Gamitrinib, a Novel Mitochondrial-Targeted Small Molecule Hsp90 Inhibitor

Descriptive Note:

Technical Report,01 Sep 2015,31 Aug 2016

Corporate Author:

The Wistar Institute Philadelphia United States

Personal Author(s):

Report Date:

2016-09-01

Pagination or Media Count:

74.0

Abstract:

The past funding cycle of the above-referenced award has supported important advances in each of the milestones and specific tasks set forth in the original SOW. Work carried out during the last budget period focused on three experimental directions towards the accomplishments of the original specific aims. First, considerable progress has been made in the full preclinical characterization of Gamitrinib in anticipation of IND filing and human testing. Specifically, ADME adsorption, distribution, metabolism and excretionstudies and a complete plasma distribution and pharmacokinetics profile of Gamitrinib in rats have been obtained. Second, we expanded the safety characterization of Gamitrinib in vitro and in vivo, and completed a non-GLP, 7 day repeated-dose study of Gamitrinib intravenous administration to Sprague-Dawley rats and Beagle dogs. These studies demonstrated encouraging drug-like properties and a favorable safety profile for Gamitrinib in vivo, with no systemic or organ toxicity in two animal species. Third, molecular studies have been carried out to further the characterization of Gamitrinib mechanism of action, antitumor efficacy in combination regimens, and the underlying role of its target, namely mitochondrial protein folding quality control in tumor progression. Supported by the present award and published in the premiere, peer-reviewed literature JCI, PLOS Biol and Cancer Cell, these studies further validated the role of mitochondrial Hsp90sas important therapeutic targets in cancer, and established Gamitrinib as a first-in-class, subcellularly-directed anticancer agent.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE