The purpose of this stage is to optimize the molecules
or compounds that demonstrate the potential to be transformed
into drugs, retaining only a small number of them for
the next stages.
To optimize these molecules, scientists use very advanced
techniques. For example, using X-ray
crystallography and in silico
(computer) modeling, they study how the selected molecules
link themselves to the therapeutic
target, for example, a protein or an enzyme. These
data allow the medical
chemists to modify the structure of
the selected molecules or compounds, if necessary, by
screening, thereby creating structural analogues.
The creation of hundreds, possibly
thousands, of analogues, is aimed at, for example,
improving the effectiveness,
diminishing the toxicity or increasing the organism’s
absorption of the drug. This phase requires close collaboration
between the
biologists and chemists,
who form a feedback loop. The biologists test the
biological properties of compounds
on biological systems while the chemists perfect the
chemical structure of these compounds in the light of
information obtained by the biologists.
Duration: from
4 to 6 months
The 100 to 200 chosen compounds are
examined in the laboratory in order to perfect
their physiochemical
properties, their pharmacokinetic behavior
and the therapeutic effectiveness.
Around twenty (20) will be selected
to be tested on animals in the preclinical
development stage.
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This optimization stage aims at developing
new substances that are more effective than known compounds.
The latter are then subjected to a specific evaluation
involving broader biological tests. In fact, the probability that a chemical sustance will become a drug depends greatly on its pharmacokinetic and pharmacodynamic evaluation (PK/PD). These studies are conducted on both in vitro systems,
for example, on human intestinal and hepatic cells, and
in vivo systems such as mice and/or rats. The blood and
urine of these animals is then analyzed by the chemists,
in order to evaluate the relative effectiveness of the
molecule in terms of intestinal absorption, body distribution,
metabolism and excretion. This discovery phase concludes with between one and
five substances, with promising biological and chemical
properties, being labelled “candidate drugs”. |
