Novel Drug Target for Bile and Cholesterol Metabolism

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$144,158.00
Award Year:
2003
Program:
SBIR
Phase:
Phase I
Contract:
1R43DK065426-01
Agency Tracking Number:
DK065426
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
ORPHAGEN PHARMACEUTICALS
ORPHAGEN PHARMACEUTICALS, 19800 MAC ARTHUR, STE 500, IRVINE, CA, 92616
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
SCOTT THACHER
(858) 625-0540
SMT@ORPHAGEN.COM
Business Contact:
TIM SCOTT
(949) 757-4131
TSCOTT@ORPHANGEN.COM
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): Regulation of bile acid metabolism is a therapeutic target for treatment of hypercholesterolemia as well as for cholestasis, the pathological buildup of bile in liver. Therapeutic options for direct modulation of hepatic bile formation and transport are limited. Orphagen proposes to develop and commercialize lead molecules that regulate gene transcription by the orphan nuclear receptor LRH-1 (liver receptor homolog-1). LRH-1 appears to stimulate reverse cholesterol transport, bile formation, and bile transport. The effort to identify the first pharmacologically active compounds to LRH-1 is part of a larger program to create drugs to structurally-related orphan nuclear receptors that regulate mammalian steroid and cholesterol metabolism. In Phase I, an indirect binding assay for compound screening at LRH-1 will be implemented based on findings from Drs. Holly Ingraham and Kip Guy at U. C. San Francisco. LRH-1 will be screened against a focused small molecule compound library developed at Orphagen. Cell-based reporter gene assays will be implemented in parallel to accelerate identification and confirmation of small molecules that regulate gene transcription by LRH-1. Drug candidates suitable for animal studies of hypercholesterolemia and cholestasis will be synthesized and tested in Phase II and a strategic partner recruited for further development.

* information listed above is at the time of submission.

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