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Small Molecule Inhibitors of C. perfringens Epsilon-Toxin

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
85317
Program Year/Program:
2007 / SBIR
Agency Tracking Number:
AI074105
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
INNOVATIVE BIOLOGICS, INC
INNOVATIVE BIOLOGICS, INC 13455 SUNRISE VALLEY DR, STE 200 HERNDON, VA 20171 3296
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2007
Title: Small Molecule Inhibitors of C. perfringens Epsilon-Toxin
Agency: HHS
Contract: 1R43AI074105-01
Award Amount: $99,097.00
 

Abstract:

DESCRIPTION (provided by applicant): The overall goal of this SBIR Phase I proposal is to find compounds that inhibit C. perfringens epsilon-toxin action using a novel approach for the inactivation of pore-forming toxins developed at Innovative Biologics, Inc. It is based on the blocking of the target pore with molecules having the same symmetry as the pore itself. Previously, we demonstrated that per-substituted derivatives of beta-cyclodextrin (beta-CD) having a sevenfold symmetry could block the heptamer ic pore formed by Bacillus anthracis protective antigen (PA) and were protective against anthrax lethal toxin action in cell-based assays and in animals tests. Since C. perfringens epsilon -toxin forms a heptameric trans-membrane pore similar to the PA por e, we propose to screen our library of per-substituted beta-CD derivatives for inhibitors of epsilon - toxin's activity. The specific aims of this Phase I study are: (1) Establish and validate assays for testing the ability of beta -CD derivatives to block the pore formed by C. perfringens epsilon -toxin and to inhibit its cytotoxic activity. (2) Test blocking and inhibitory activity of compounds from a representative library of per-substituted beta -CD derivatives and select the most potent compounds for f urther development as anti-toxin drugs. Provided that effective inhibitors of epsilon -toxin are found in this feasibility study, in Phase II we will utilize our initial testing data and the crystal structure information available for C. perfringens epsilo n -toxin in concert with computational chemistry to design additional beta-CD derivatives with enhanced affinity to the epsilon -toxin pore. The designed compounds will be synthesized and tested in vivo and in vitro with the eventual goal of finding new th erapeutics against C. perfringens epsilon -toxin. Project Narrative: Epsilon toxin produced by Clostridium perfringens is one of the most lethal bacterial toxins. It is regarded as a potential biological weapon and is included in the list of category B pri ority agents. Currently, there is no effective treatment for the epsilon -toxin-mediated intoxication; therefore, a great need exists for the development of therapeutics against this biodefense toxin.

Principal Investigator:

Vladimir A. Karginov
7036225749
VAK@INNOVBIO.COM

Business Contact:

Vladimir Karginov
vak@innovbio.com
Small Business Information at Submission:

INNOVATIVE BIOLOGICS, INC
INNOVATIVE BIOLOGICS, INC 13455 SUNRISE VALLEY DR, STE 200 HERNDON, VA 20171

EIN/Tax ID: 113427236
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No