"Molecular design is
complicated
and hard, and it is getting harder and more complicated everyday.
For one thing, it is inherently
multi-objective,
with improvement in one attribute - e.g., potency - often coming at the
expense of another - e.g., bioavailability. Moreover, attributes
such as half-life exhibit optima as well as trends, requiring a careful
balancing act between
being too long and too short.
Given that complexity, it makes sense to bring as many disciplines to
bear on the problem as possible; cranking blindly through black box
models or a synthetic strategy of methyl, ethyl, butyl, futile ... will
not get the job done. That is why drug discovery and development
has evolved into a team activity, with people from many disciplines
working together.
Biochemical Infometrics - the company - was founded with the aim of
making a broad
range of experience available to smaller companies. The
company closed down in January 2010 when I took on my curent job
as Director of Life Sciences at
Simulations Plus, Inc.
SLP provides consulting services as well as pharmacokinetic simulation,
ADMET
modeling and screening triage soft- ware, which will afford
me opportunities to share my inter- and transdisciplinary perspective
with client companies of many sizes.
On a personal note, my new role is providing me with valuable
experience in the ADMET/PK arena, which I have been interested in for
many years."
Hedge Your Bets to Come Out Ahead
If you watch the people who
make a living at racetracks, you will see
that they do not pick winners. Instead, they typically bet on
several horses to Win, Place or Show. In many ways, drug
development is a similar game, in that you are operating with limited
and imperfect information and chance plays a big part in how
your corporate gambles turn out.
Molecular modeling can add value - a
lot
of value - by helping you spread your risk more rationally across leads
and candidates. Most people already appreciate the importance of
cultivating structural diversity when picking compounds for follow-up
acquisition or synthesis, but there is as much or more to be gained by
diversifying across likely ADMET risks. Being able to make
relevant and
reasonably reliable predictions in this arena within the realm of
well-explored chemistry is critical. Such predictions are still
something of an
art when one ventures into new areas, but that is where the value added
is.
Simulations Plus is
first and foremost about simulating pharmacokinetics and
physiology. This empirical orientation leads the company to value
QSAR models as a way to estimate parameters that are not readily
measured, and leads to an emphasis on good science, robust methodology,
careful curation and attention to detail; Bob feels right at home.
©
2009 Biochemical Infometrics; all rights reserved.
