Discovery
and Optimization of New Benzimidazole- and
Benzoxazole-Pyrimidone Selective PI3KBeta Inhibitors for the
Treatment of Phosphatase and TENsin homologue (PTEN)-Deficient
Cancers" |
The
protein plays an important role in regulation of cellular
processes and alteration of the PTEN function through
mutation, may lead to the disruption of normal cellular
functionin.
The
processes that are usually affected include the cell cycle,
protein synthesis, growth, migration, survival signalling and
DNA repair.
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Secondary
structure is represented in cartoon visualization that alpha
helicies are pink,
beta sheets are yellow,
and regions without secondary structure are white. Non protein
structures are drawn in wireframe.
The
PTEN protein also influences the functioning of
phosphatidylinositol 3-kinase (PI3 K) and protein kinase B
pathway (AKT). The compound phosphatidylinositol
3,4,5-trisphosphate (PI(3,4,5)P3) promotes the AKT
pathway, which leads to cell proliferation, glycolysis,
cell survival and inhibits apoptosis.
The same
secondary structure in another view showing from the top and in
color group. The enzyme
phosphatidylinositol
4, 5-bisphosphate [PI(4,5)P2] on the other hand, reverses
these effects by inhibiting cell proliferation, glycolysis,
cell survival and promotes apoptosis. The enzyme PI3K
normally converts [PI(4,5)P2] to[PI(3,4,5)P3], while PTEN
protein converts [PI(3,4,5)P3] to [PI(4,5)P2].
Zooming view shows a
unique ligands VMN.
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