Our current Product
Pipeline is based on single chemical entities and mixtures.
In the future we expect to integrate new technologies, such as
proteomics, in our drug discovery efforts.
Specifically, our strategy is to expand the use of cytokines in in
vitro assays into the development of cytokine fingerprints.
We also want to integrate information from proteomic services and
published disease spectra to establish novel TCM-validating approaches that will
ultimately lead to generation of new prescription drugs.
Single Chemical Entities
We will continue to search for natural products as single chemical entities from TCM exhibiting hematopoiesis, immune modulation and cancer bioactivities. Collaborators have historically constituted a major source of our natural products.
with hematopoiesis, immune modulation and cancer bioactivities described in the
scientific literature will be evaluated in-house for bioactivity.
These natural products may be obtained as in the past, through
arrangements with collaborators. However, for the future we believe that we can purchase
interesting natural products from vendors.
Indeed, chemical vending is a growth industry in China.
We can obtain quantities of natural products ranging from research
supplies to bulk amounts of cGMP material.
Once a natural
product from TCM with an optimal therapeutic profile has been identified, it can
be modified. to produce a derivative as a single chemical entity.
With the derivative strategy, we start with a natural product that has a
desired therapeutic. The objective of a derivative strategy is to chemically
modify the lead structure to increase potency, reduce toxicity and/or optimize
bioavailability. When a series of
chemically modified derivatives are prepared and tested, a structure activity
profile is generated that can lead to further improvements or can provide a
development candidate. In addition,
we can obtain a composition of matter IP position for a development candidate.
We currently use
primary in vitro screens when
assessing bioactivity including the induction of cytotoxicity in Jurkat T
lymphoid tumor cells as an indicator of anticancer activity (MTT assay), and
inhibition of IL-2 production in Jurkat cells as an immune suppression read-out.
Secondary in vitro screens
allow more precise determination of the activities of test compounds and include
both anticancer and immune suppression assays.
New technologies bridging Eastern and Western medicines
complex extracts as drugs are a basis of success of TCM.
Water extracts of a single plant or preferably multiple plants have been
traditionally used in TCM. Spray
drying or precipitation of these aqueous extracts and formulating the resulting
solid in tablet or capsules is a recent variation.
The value of these mixtures appears to be that a combination of weakly
acting molecules is a better medicine than a single chemical entity that is
potently active. In addition, TCM
based extracts are thought to be less toxic in general than single chemical
The Western drug
paradigm has been ‘one molecule affecting one receptor or one enzyme.' This
approach is less effective when more complex diseases are targeted.
pharmaceutical technology has advanced its capabilities for defining mixtures
medically. These technologies,
genomics and proteomics, will soon be used to define single chemical entities as
potential prescription drugs. Traditional
pharmaceutical discovery has employed single receptors or single enzymes to
characterize single chemical agents. Proteomics
is a powerful new tool in pharmaceutical discovery because proteins are
effectors of health/disease on a molecular level.
As a tool, proteomics can be used to characterize the state of complex
biological systems. The proteomic
tool combined with Pharmagenesis unique expertise will allow for the first time
the characterization of mixtures. Currently, proteomics is being used in
detection of certain cancers, which emit specific proteins, such as, HER-2/neu
Many different proteomic tools are now available.
As a result of the availability of these tools, Clinical Proteomic
Databases are emerging becoming available.
In the very near future, clinical proteomic databases will characterize
disease spectra. For example, the NIH (National Institute of Health), FDA (Food
and Drug Administration) and NCI (National Cancer Institute) have both Prostate
Spectra and Ovarian Spectra.