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Building
from a successful demonstration of effect
in predictive animal models our lead
optimization process continues to develop
the "continuous hypothesis testing
model" started in the hit and lead
identification phases, whereby ideas
about potency in biochemical and cellular
in vitro and in vivo systems are challenged
at an early stage for therapeutic viability.
The emphasis is on demonstration of
biological activity in meaningful in
vitro, cellular, and animal models with
continued exploration the factors controlling
compound activity at both the biological
target and against physicochemical,
ADMET, and PK/PD parameters.
Structure activity relationships are
established via the preparation of focussed
compound arrays, and iterative use of
drug design tools. A great importance
is placed on the physicochemical properties
necessary for oral administration, such
as solubility, bioavailability and formulation. |
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