Ligand Scientists Discover Tissue-Selective Female Hormone Mimics

The Journal of Medicinal Chemistry Highlights Discovery of First Progesterone Mimic To Act Selectively On Uterine Cells And Reproductive Tract With Reduced Impact On Breast Cells

SAN DIEGO, Calif., June 23, 1998--Scientists from Ligand (LYE-gand) Pharmaceuticals Incorporated (Nasdaq: LGND) have discovered "designer" progestins that show a protective activity in the uterus without concomitant stimulation of breast-cell growth. Research surrounding this discovery was released today by the Journal of Medicinal Chemistry, a leading peer-reviewed journal for discoveries in the medicinal chemistry field. Data featured in the journal describe two novel non-steroidal progestin compounds, (S)-LG120746 and (S)-LG120747 that were tested in animal models and demonstrated the ability to selectively stimulate tissues within the body.

Currently available steroidal progestins, which are most often used in hormone replacement therapy and birth control, do not exhibit this ability to discern between tissues or cell types. All progestins used in clinical practice today are steroids, and while they provide a positive benefit, they also carry the potential of enhancing cancer risk in women since they can stimulate cellular proliferation in several types of tissues--most notably breast tissue.

"With this publication, Ligand has revealed the discovery of a completely novel progesterone receptor pharmacophore that may have distinct clinical advantages over currently available steroidal progestin therapies," said Dr. Andrés Negro-Vilar, Ligand Senior Vice President and Chief Scientific Officer. "These compounds should provide a clear benefit when used in hormone replacement therapy and other important female health applications."

Ligand's research team recognized (S)-LG120746's and (S)-LG120747's progestin effect through the application of three in vivo tests or assays. The scientists applied these assays to the

Contact: Mary Kenny
Ligand Pharmaceuticals Incorporated

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