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In
September 2006, NicOx selected NCX 6560 as a
new internal development candidate. NCX 6560
is a nitric oxide-donating derivative of a
commonly used statin drug, which has the
potential for broadened and increased benefit
in cardiovascular disease. Statins represent
the most effective and best tolerated drugs
for lowering abnormally raised cholesterol and
have consequently become the world’s best
selling class of pharmaceuticals, with
combined global sales of $20.1 billion in
2005.
NCX
6560 has the potential to target
atherosclerosis and endothelial dysfunction
through a multi-pathway approach. The capacity
of the nitric oxide-donating moiety to
counteract vascular inflammation and
endothelial dysfunction should act in concert
with the cholesterol lowering activity of the
statin portion, to favorably influence the
composition, structure and stability of
atherosclerotic plaques.
Atherosclerotic
plaques are believed to be the root cause
underlying the majority of cardiovascular
diseases and their development is a
complicated, multi-step process, which is
believed to involve both raised cholesterol
levels and deficient nitric oxide signaling.
The process starts with the formation of
fat-containing lesions on blood vessel walls,
due to abnormally high plasma cholesterol
levels, which has a number of detrimental
effects. These include infiltration of immune
cells, inflammation and abnormal proliferation
of smooth muscle cells, which are all
processes which have been linked to abnormally
low nitric oxide release from the endothelium.
Furthermore, nitric oxide is involved in
regulating vascular function and platelet
activation and malfunction of these two
systems can lead to disruption of the
atherosclerotic plaque, clotting and an acute
cardiovascular event.
Preclinical
results support the rationale for using
NicOx’ nitric oxide-donating technology to
develop the next generation statins. The
nitric oxide released from NCX 6560 appears to
markedly increase the non-cholesterol lowering
activities of statins. For example, NCX 6560
has demonstrated superiority to a widely used
statin in a number of preclinical models,
including those related to anti-platelet and
anti-thrombotic activity, anti-inflammatory
activity and endothelial function.
Furthermore, in different models, NCX 6560 has
demonstrated either a similar or superior
serum cholesterol lowering effect, compared to
an equivalent dose of the reference statin.
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