tommysdad, I don't think that its clear which activity impacted HIV, and RU-486 can influence progestins as well as glucocorticoids. In addition to the Progestin program with AHP, LGND has a glucocorticoid program with ABT. I agree that applications to HIV is probably years away. The current study was at the research level (and LGND has studied RU-486 as well as many analogs).
Here's some background info on RU-486:
Antiprogestins: Modulators in
Reproduction
IRVING M SPITZ & ISRAEL AGRANAT
Best known as the major component in the abortion pill,
antiprogestins
offer a wide range of medical benefits for female health
In mammals, the steroid hormone progesterone plays a critical
role in reproduction, and is essential for starting and
maintaining pregnancy. Progesterone exerts its biological effect
by entering the cell and binding to a specific protein known as
the progesterone receptor. This receptor belongs to a family of
nuclear receptors. This family includes receptors not only for
the steroid hormones (oestrogens, progestins, androgens,
glucocorticoids, mineralocorticoids and vitamin D) but also for
the thyroid hormones and the retinoids. In contrast to receptors
for protein hormones, the steroid hormone receptors are situated
in the nucleus of the cell. In the absence of progesterone, the
native receptor exists in an inactive form. Binding of
progesterone to the receptor activates it, and it then functions
as a transcription factor in the cell nucleus to enhance the
expression of specific genes initiating the biological actions
of progesterone.
Following the discovery of the progesterone receptor, scientists
recognised that an agent which
inhibited progesterone's binding to its receptor - an
antiprogesterone or progesterone antagonist -
would open many therapeutic possibilities in female reproductive
health. The search for such an
antiprogesterone lasted more than a decade. Its eventual
discovery was somewhat fortuitous, since the scientific team
were in fact looking for a glucocorticoid antagonist, an agent
which inhibits or blocks the action of cortisol, a hormone
essential for life. Under certain circumstance, cortisol is
secreted in excess and produces untoward effects. In 1981,
Daniel Philibert, Roger Deraedt and Georges Teutsch from the
French pharmaceutical company Roussel Uclaf announced the
discovery of RU 38486, a glucocorticoid antagonist with
antiprogestin properties (1). RU 38486 was subsequently
abbreviated to RU 486, and is now known by its generic name
mifepristone. It was the first antiprogestin to be developed.
The original studies showed that this synthetic steroid bound
strongly to both progesterone and
glucocorticoid receptors. However, unlike the natural occurring
hormones, mifepristone inhibited the effects of progesterone and
cortisol, acting as a potent progestin and glucocorticoid
antagonist (inhibitor). For clarification purposes it should be
noted that an agonist is a drug which binds to a specific
receptor producing a response. An antagonist, on the other hand,
binds to the same receptor but blocks the response seen with the
agonist. |
