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Optimization of Small Molecule Botulinum Neurotoxin Inhibitors

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
80274
Program Year/Program:
2006 / SBIR
Agency Tracking Number:
AI069637
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
HAWAII BIOTECH, INC.
99-193 AIEA HEIGHTS DRIVE, SUITE 200 AIEA, HI -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2006
Title: Optimization of Small Molecule Botulinum Neurotoxin Inhibitors
Agency: HHS
Contract: 1R43AI069637-01
Award Amount: $1,019,214.00
 

Abstract:

DESCRIPTION (provided by applicant): Medicinal and computational chemistry methods will be used to optimize validated hit compounds found to inhibit botulinum neurotoxin. These inhibitors, discovered through in silico docking and confirmed with an in vitro fluorescence resonance energy transfer assay, show excellent properties of 'leadlikeness' and are well- suited to further investigation as possible drug candidates. The specific aims of the project in phase I are to identify a lead series and a backup series from current hits with the following characteristics: A. in vitro inhibition of botulinum serotype A light chain (BoNT/A LC) at submicromolar concentrations; B. demonstrated inhibition of BoNT/A toxicity in ex vivo and in vivo assays; C. selectivity for inhibition of BoNT/A LC over MMPs at least 10-fold; and D. a favorable PK profile as demonstrated by preliminary PK studies in mice. In phase II, these series will be further optimized to provide drug candidate compounds which will be ready to enter the Preclinical Development stage and move on to Human Safety Testing. The possibility of pursuing a broad-spectrum BoNT inhibitor will be considered based on multiple serotype assays performed in Phase I. A safe, orally available small molecule inhibitor would be the most desirable practical therapy to address the specific threat of the use of BoNT in bioterrorism. Though an effective antitoxin vaccine exists, there are issues involving the growing beneficial medical uses for BoNT which make widespread civilian vaccination undesirable. At present, there is no approved small molecule therapeutic. Hawaii Biotech has discovered promising 'leadlike' validated hit compounds which will be optimized in a focused medicinal chemistry effort toward the long-term goal of a small molecule drug for the treatment of BoNT intoxication that is suitable for use in a large-scale bioterrorism attack.

Principal Investigator:

Sean Omalley
8087921321
SOMALLEY@HIBIOTECH.COM

Business Contact:


8087921333
Small Business Information at Submission:

HAWAII BIOTECH, INC.
HAWAII BIOTECH, INC. 99-193 AIEA HEIGHTS DRIVE, SUITE 200 AIEA, HI 96701

EIN/Tax ID: 990214983
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No