"Molecular design is
complicated and hard, and it is getting harder and more
complicated every day. 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, futyl ... 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 my broad range of experiences
available to smaller companies. It closed down in
January 2010 when I became Director of Life Sciences at
Simulations
Plus, Inc., which provides consulting services as
well as pharmacokinetic simulation, ADMET modeling and
drug design software. Working there has afforded me
opportunities to apply my inter- and transdisciplinary
perspective to many challenging modeling problems in the
DMPK area. My current role as a Senior Research Fellow
gives me with the chance to focus on mentoring, getting
back to the (virtual) bench, and writing up more
of the research I have contributed to in the near decade
since I joined the company."
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.
Intelligent molecular design can add value - a
lot of value - by
helping you spread your risk 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 and PK
risks. Being able to make relevant and reliable
predictions of the corresponding properties
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.
