Current hGH (human growth hormone) therapy, approved for the treatment of pituitary dwarfism, requires chronic administration by injection and is exceedingly expensive (up to $30,000 per patient annually). This project focuses on the discovery of novel low molecular weight pharmaceuticals which act by transcriptional activation of the endogenous hGH gene. In Phase I, the promoter and first intron of the hGH gene were cloned and fused to a luciferase reporter vector. We also cloned the promoter of a homologous gene termed hGHN. Both of these promoter-reporter constructs exhibited extreme tissue specificity, showing more than a thousand-fold greater activity in pituitary cells than in fibroblasts. Regulation by known modulators of hGH transcription was also observed, confirming that these vectors faithfully represented the transcriptional regulation of the endogenous hGH gene. In Phase II, stably transfected cell lines will be used to search for compounds which transcriptionally activate the hGH gene; specifically, for compounds which act either as GHRF (growth hormone releasing factor) agonists or act directly via the GH transcription factor, Pit-1. The primary screen will employ a unique, fully automated robotic screening system which enables over 100,000 compounds to be screened per year. Lead compounds will be sought from a collection of fungal fermentation broths and from combinatorial peptide libraries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44DK044056-02
Application #
3507484
Study Section
Special Emphasis Panel (SSS (B6))
Project Start
1991-09-01
Project End
1995-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Osi Pharmaceuticals, Inc.
Department
Type
DUNS #
City
Uniondale
State
NY
Country
United States
Zip Code
11553