One treatment by two mechanisms. First, it regulates

One of the main reasons
for loss of sensitivity to hormone therapy in breast cancer patients is the development of Acquired drug
resistance. Mechanically, the abnormal activation of the Akt /
mTOR signaling pathway and the overexpression
of LMTK3, are the main
factors involved in the generating of this résistance. These factors constitute therefore a very interesting field of
research, and approaches aiming to target this mechanism by abrogating
resistance induced by Akt
and lmtk3 are therefore of great relevance of treatements breast cancer Lemur tyrosine kinase-3 (LMTK3), a member of the
serine-threonine tyrosine kinase family, plays a central role in endocrineresistance, It has been considered as a promising therapeutic target in the breast
cancer treatment. Indeed, this protein is incriminated in theinduction of resistance to hormonal treatment by two mechanisms.   First, it regulates of ESR1 transcriptional activation by inhibiting PKC,which
leads to a decrease of phosphorylated AKT (Ser473), responsible for the FOXO3
stabilization which allows the increase of the Er? transcriptional activity.
Secondly, it allows the ER? protein direct phosphorylation, protect it from
protease degradation mediated by ubiquitin(Ub).  Thus, in front of
resistance to endocrine treatment, inhibition of LMTK3 resulted in
re-sensitization to treatment, and increased AKT
phosphorylation and other unidentified PKC targets The Akt1 is one of the
3 closely related serine / threonine-protein kinases(AKT1, AKT2 and
AKT3), called AKT kinase.
This protein plays an important role in cell
proliferation and survival, It seems to be at the crossroads of different signaling pathways and acts as a
transducer for many functions.  The overexpression of LMTK3 and AKT has been observed
in several types of humans cancer, including breast cancer, bladder cancer, lung
cancer (anaplastic small cell), and gastrointestinal cancer(Gastric and
colorectal) However, recent
studies have demonstrated that inhibition of
LMTK3, and pathway
(Akt and /or mTOR) deletion , restore
sensitivity to anti-estrogen treatment in breast cancer
cells, These are, therefore, two proteins that play a important role in the cancer therapy development , these
molecules have characteristics necessary for design of effective and
reliable small drug molecule. The identification of lead compounds
with a pharmacological activity against a biological target
and the optimization of their
properties are the starting points in the early stages
of drug discovery. This discovery itself is a complex process that
would take 12 to 15 years and cost more than $ 1 billion. The treatment effectiveness is the prerogative of either a
single anticancer molecule with a specific target, or the combination of several molecules thus aiming
different therapeutic targets. Consequently, the pharmaceutical industry
adopted, firstly, the virtual screening of chemicals products  against a
relevant therapeutic target as a means of identifying new lead compounds, and
secondly the computational methods (in silico) in development  process  of these compounds before the preclinical stage, particularly in the
physicochemical, pharmacodynamic and pharmacokinetic properties  study.
Quantitative structure-activity relationship (QSAR) models, are quantitative
regression methods which enable to link the chemical structure to the biological activity. They haveextensively been applied
in several scientific disciplines: chemistry, biology and toxicology.
QSAR models are considered
a scientifically credible tool for predicting and classifying biological activities of untested chemicals. This tool has become an essential method of
discovery and leading edge optimization to direct development in the pharmaceutical industry