This assistance can
span a range of activities, including selection
of representative HTS hits for Hit-to-Lead
resynthesis, the design of individual compounds
and lead-optimization libraries in early-stage
lead optimization, or later-stage
multi-parametric optimization to minimize
potential ADME/TOX risks while maintaining
activity.
BioPredict offers an established track record in
applying state-of-the-art structure-based
technology to the design of compounds and
libraries to increase activity. Where multiple
structures are available within a target class
such as kinases, BioPredict has applied
proprietary tools to not only optimize activity
but also to optimize target specificity – a
fundamental problem in many current target
classes. BioPredict scientists have used these
methods successfully in past projects to:
-
increase
affinity of leading compounds by several
orders of magnitude
-
achieve
exquisite target specificity to single
targets
-
achieve
exquisite target specificity to dual desired
targets
-
identify
alternative backup series patentably
distinct from initial series
-
increase the
number of highly active compounds in a
target series for SAR and patent purposes
-
identify
synthetic directions for compounds specific
to a target subclass
When there is no
structure available for the target protein or a
close homolog, BioPredicts scientists can
design a synthetic strategy to explore a lead
series SAR and to use it to optimize leads.
Ligand-based methods include derivation of
three-dimensional pharmacophoric hypotheses, 3D
superposition of molecules to develop of
field-based 3D QSAR models, and application of
learning-based methods. Whether structure-based
or ligand-based, lead optimization is
intrinsically data intensive and proceeds best
when it is hypothesis driven. Computational
methods become imperative as the number of
compounds synthesized becomes more than a few
dozen, not only to derive and evolve hypotheses
but also to keep track of the diversity space
already explored around a lead molecule, to
fold explored space into existing hypotheses,
and to identify portions of diversity space not yet
explored. Later-stage lead optimization is
multi parametric by nature. Current drug
discovery is an information-rich endeavor that
can generate a wealth of information on
affinity, ADMET, cross-reactivity, and more -
all of which needs to be correlated with
chemical structure to produce a viable clinical
candidate. BioPredict brings the experience
and technologies required to tackle this
data-driven paradigm effectively, bringing
candidates to clinic faster providing detailed
documentation for patent position and for
filing. |