John, LGND is fairly complicated from almost any perspective.
I try the technology a couple of times. Its easy for me to
get too technical, so feel free to ask if something isn't computing.
In general, LGND uses a panel of receptors to screen drugs.
I'll start with the the non-polypeptide hormones, because they
are somewhat more straight forward. The non-polypeptide hormones
are small molecules which the big pharms love. Their medicinal
chemists can make then in the lab using common chemicals. They
are relatively cheap to make and can be taken orally (as a pill).
These drugs go into the bloodstream and then to cells where they
diffuse in and bind to an appropriate receptor. The drug (hormone)
binding causes the receptor to change its shape and become "activated".
This activated receptor the goes to the nucleus (where the DNA and
genes are) where it forms complexes (usually containing other
activated receptors) which then bind to specific sites on the DNA
and turn appropriate genes on and off. LGND uses these hormone
receptors for screening. They use a panel and get several pieces
of information. A positive means not only that the drug bound to a specific receptor,
but the binding caused the receptor to become "activated" and turn appropriate
genes on or off.
This approach is a major improvement over older animal tests which are
expensive and take considerable time, as well as "grind and bind" tests
which grind up tissues and then see if the hormone binds to the extract
(specificity is difficult to determine and the assay doesn't indicate
whether the biding "activated" the receptor). Although the screening
is rather straight forward, LGND is in an excellent position because they
have a large panel of recpetors isolated and their consultants
isolated and sequenced many of the first receptors (so they have
broad patent protection). Its easy to find alliance partners, because
the big pharms can make huge libraries of compounds (by chemically
modifying existing horrmones or drugs), but they don't have
a cheap and reliable way to screen them. Some of the hormones or
analogs that are currently on the market are JNJ's Retin-A and Renova,
Roche's Accutane and Vessanoid, AHP's Premarin, Zen's Tomaxifan,
a variety of steroids for inflammation, etc. LGND seeks to use
its screening ability and corresponding pre-clinical and clinical data
to produce improvements on the existing compounds. The STAT technology
does the same type of screening with polypeptide hormones. These
hormones bind to the cell surface and use a variety of molecules to send
a signal to the nucleous where the end products are much like the
receptors described above (they get activated, form complexes, and
then turn specific genes on and off). LGND is looking for small molecules
that will do the activating. Such compounds can be taken orally instead
of injection which is the administration route for most of Biotechnology's
compounds (Epogen, Neupogen, Avonex, Betaseron, Myotropin, Humalon,
Aldesleukin, leptin, etc.).
Henry |
