Small Molecule Blockers of B. anthracis Toxin

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,703,293.00
Award Year:
2004
Program:
SBIR
Phase:
Phase II
Contract:
2R44AI052894-02
Award Id:
60465
Agency Tracking Number:
AI052894
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
INNOVATIVE BIOLOGICS, INC, 13455 SUNRISE VALLEY DR, STE 200, HERNDON, VA, 20171
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
169174146
Principal Investigator:
VLADIMIR KARGINOV
(703) 622-5749
vak@innovbio.com
Business Contact:
VLADIMIR KARGINOV
(202) 546-4367
vak@innovbio.com
Research Institution:
n/a
Abstract

DESCRIPTION (provided by investigator): Results from our SBIR Phase I project demonstrated that beta-cyclodextrin derivatives designed to block the trans-membrane channel formed by B. anthracis protective antigen (PA) can inhibit the cytotoxic effects of anthrax toxin at low micromolar concentrations. Based on successful completion of the feasibility study, the overall goal of our Phase II project is to select the best drug candidates for anthrax treatment. To achieve this goal we will perform large-scale design, synthesis and screening of chemical libraries, and test the best candidates in small animal studies. The specific aims of this Phase II study are: (1) Utilize crystallographic coordinates and initial testing data in concert with computational chemistry to design additional beta-cyclodextrin derivatives with increased affinity to the PA pore. (2) Optimize a cell-based assay to screen the inhibition of the anthrax toxin cytotoxic effect, establish and validate cell-based and biochemical assays to test chemical compounds for the ability to block the PA channel. (3) Synthesize representative libraries of beta-cyclodextrin analogues, and screen them using biochemical and cell-based assays. (4) Perform toxicity and efficacy tests in mice using at least five compounds with inhibitory activity at nanomolar concentrations to select drug candidates. Long term goals include subsequent preclinical and clinical studies that will lead to the development of a new anti-anthrax treatment.

* information listed above is at the time of submission.

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