Version 2.1.1.0 |
![]() |
![]() ![]() ![]() |
Abstract
Grant Number: 5R43AI052680-02 PI Name: OWENS, ALBERT H. PI Email: albert.owens@fasgen.com PI Title: MEMBER Project Title: Novel Compounds for Improved Treatment of Tuberculosis Abstract: DESCRIPTION (provided by applicant): In 2000, the U.S. had over 16,000 cases of infectious tuberculosis and an estimated 10-15 million latent cases. Despite prolonged treatment regimens with significant side effects, reports of drug resistant TB in 43 states, and an estimated $345 million market opportunity, few new drugs to treat TB are in development. FASgen's SBIR Phase I goal is to choose a lead anti-tuberculosis candidate from 6 molecules active in vitro against Mycobacterium tuberculosis. Phase I specific aims are: 1) resupply candidate compounds and determine purity and chemical and biological stability; 2) determine minimum inhibitory concentrations (MICs) against a panel of mycobacteria in vitro; 3) determine in vitro cytotoxicities (lC50s) against Vero cells; 4) determine maximum tolerated dose (MTD) and dose limiting toxicity in mice for compounds with selectivity index (MTD/IC50) >10; 5) test the best compound in a murine inhalation model of TB; 6) verify that the MTD is not substantially different in immunocompromised (beige) mice; 7) test whether the best anti-tuberculosis compound is also active against M. avium in an immunocompromised mouse model; 8) repeat/confirm efficacy in animal models. In SBIR phase II, the lead compound will undergo safety/toxicology testing in animals and Phase I/Il safety and Phase II efficacy testing in man, most likely against multidrug resistant TB.
Thesaurus Terms:
Mycobacterium tuberculosis, antitubercular agent, drug design /synthesis /production, tuberculosis
Mycobacterium avium, chemical stability, cytotoxicity, dosage, drug screening /evaluation, pharmacokinetics
SCID mouse, laboratory mouse
Institution: FASGEN, INC. 5210 EASTERN AVE BALTIMORE, MD 21224 Fiscal Year: 2003 Department: Project Start: 01-AUG-2002 Project End: 31-JUL-2004 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1
![]()
![]()
![]()