application): Pharmacological inhibitors of restenosis following balloon angioplasty are needed to inhibit the proliferation smooth muscle cells. Lion Pharmaceuticals and its collaborators Dr. Chatters at Johns Hopkins University propose to develop inhibitors based on novel enzymatic drug target UDP-galactose: glucosylceramide, Beta-1-4 galactosyltransferase (GalT-2; LacCer synthase). The mitogenic stimulation of the muscle cells leads to elevated levels of GalT-2 activity and its product LacCer, appear to act as both a second messenger and a mitogen in its own right. The primary hypothesis in this grant is that inhibition of GalT-2 following balloon angioplasty should reduce and or prevent restenosis. A combinatorial library of approximately 500 compounds based on the structure of a non-selective inhibitor, D-PDMP, will be screened against a partially purified preparation of GalT-2. Candidate inhibitors from the screening process will be tested for their effectiveness in preventing smooth muscle cells proliferation. Specificity of candidate inhibitors for GalT-2 will then be evaluated by screening a family of unrelated enzymes that are important intracellular enzymes. Based on these studies they will proceed with Phase II testing in animal models of restenosis and initiate both formulation and safety studies in order to complete an attractive package for outlicensing and commercialization by Lion.

Proposed Commercial Applications

NOT AVAILABLE

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43HL060367-01
Application #
2645515
Study Section
Special Emphasis Panel (ZRG3-SSS-Z (01))
Project Start
1998-04-01
Project End
1998-09-30
Budget Start
1998-04-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Lion Pharmaceuticals, Inc.
Department
Type
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21230