
API currently has projects ongoing in seven therapeutic areas, of which the
Estrogen program is the most advanced.
Estrogen Project: API designed an estrogen (PDC-7) using its estrogen
pharmacophore. PDC-7 was predicted to be more active than the natural hormone
estradiol. Synthesized by Magellan Laboratories, PDC-7 was tested in classical
in vivo estrogen assays at an independent institution and was found to be 2-3
times more potent than estradiol, thereby providing validation of the
technology. PDC-7 was a poor binder to the estrogen receptor (approximately
15%) relative to estradiol (100%) and thus would not have been selected as a
candidate based upon protein receptor based technology. API has submitted a
patent application on PDC-7 for use in estrogen responsive targets including
hormone replacement therapy (HRT), Alzheimer's disease, stroke and
contraception.
Neuroprotection Project: The goal of this project is to identify compounds
that may be useful in Alzheimer's disease and stroke. Initial in vitro
biological testing in one assay system has been completed and results
demonstrate that one of API's compounds is neuroprotective.
Oncology Project: A novel class of compounds designed using API's technology
has recently been shown to inhibit the growth of breast cancer cells in vitro.
The activity of these compounds correlates with the direct binding of the drugs
to DNA. The experiments were conducted independently and were recently
published providing further validation of the technology. One of the compounds
is 7 times more potent in these assays than tamoxifen, a leading drug used in
the treatment of breast cancer.
Sedative Project: A sedative pharmacophore has been created as well as a
sedative search engine. In initial phases of in silico testing, benchmark
studies indicate that the search engine is effective in identifying known
sedatives. Candidate structures are being evaluated for further development.
Computer databases of other CNS drugs (e.g., antidepressants) are also being
constructed
Diabetes/Anti-Obesity Project: API has developed pharmacophores and
associated search engines for certain oral anti-diabetic drugs. API is also
currently evaluating confidential and structural data on novel compounds that
lower glucose and lipid levels in vivo.
Impotence Project: API has recently developed a search engine for
vasodilators that are known to have activity in erectile dysfunction. The
search engine has been effective in capturing various compounds known to have
vasodilator effects. Initial data suggest it may be possible to develop a
oral drug having beneficial effects for the treatment of impotence as well as
diabetes, a well known cause of erectile dysfunction.
Additional Targets: API has created a Cardiovascular Disease project as
recent research has indicated that API's technology may be applicable to the
development of certain cardiac drugs. A search engine for cardiac drugs has
been constructed. In light of the events of September 11, API has also created
an antibiotic search engine for compounds like Cipro that are effective against
Anthrax. Promising leads have been identified including compounds with
structures unrelated to Cipro or other fluoroquinolones.