Resistance to macrolide antibiotics has increased at alarming rates in recent years, driving the need to develop new and more effective antibiotics. The long term objective of this proposal is to develop a novel 16-membered macrolide antibiotic that is active against erythromycin-resistant Streptococcus pneumoniae and other Gram positive pathogens and which can be produced at reasonable cost. The proposed compound is designed to exhibit its potency through the novel mechanism of synergistic multi-domain ribosomal binding. Consequently, the compound should not induce macrolide resistance and evade all known efflux mechanisms that confer macrolide resistance. Phase I is a proof of principle project to produce a small series of derivatives of a 16- membered macrolide that is a readily available fermentation product, and determine whether the derivatives bind to domain II of the ribosomes and exhibit increased potency against macrolide-resistant strains. Phase II Specific Aims will be to optimize the derivatives to achieve oral bioavailability. Lead compounds will be examined in vitro and in animals for efficacy, toxicity and pharmacokinetics with the intent of advancing one or more to clinical development.

Proposed Commercial Applications

Clinical development candidates could be commericialized as anti-infective agents only after approval by the appropriate regulatory authorities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI050305-01
Application #
6404753
Study Section
Special Emphasis Panel (ZRG1-SSS-K (10))
Project Start
2001-06-15
Project End
2003-05-30
Budget Start
2001-06-15
Budget End
2002-05-30
Support Year
1
Fiscal Year
2001
Total Cost
$296,598
Indirect Cost
Name
Kosan Biosciences, Inc.
Department
Type
DUNS #
932981319
City
Hayward
State
CA
Country
United States
Zip Code
94545