PATHOLOGICAL MODELING BY DRUG REPULPOSING

PATHOLOGICAL MODELING BY DRUG REPOSITIONING

Abstract: Repositioning: an alternative for drug development, but also a method of modeling a complex biological system such as the process of oncogenesis (cancer. References Articles :1- m/s n° 6-7,vol 35, juin-juillet 2019 / ,2- Delahaye-Duriez Genome Biology ( 2016 17-245 . Modeling the tumor to defeat cancer: the objective being to obtain a modele behaving like human cancer in vivo In fact, in oncology, cell cultures, model in vitro, and experimental animal models, model in vivoo, only weakly reflect reality. The elements of STROMA are associated with all stages of tumor progression. Thus the cell culture model is stroma-free, while in animal models the stroma originates from the host. consequently the two medeles are never representative of human pathology.

Repositioning of drugs that many represent the preclinical study design , model of a carcinoid tumor. the repositioned drug inducing a complex phenotype . At selected drug candidate, combines the phenotypic characteristics of these hit drugs (indication and side effects / ; chemical structure and biological properties (targets, networks of biological interactions /; the side effect being associated) to underlying genetic changes, evoking the process of oncogenesisas

This target repositions the drug candidate GPCR transmembrane receptor involved in the regulation of genetic expressions in the direction opposite to that observed in pathology ,,. and as the GPCR is an allosteric protein by nature manifesting its activity by change of conformation. The competitive antagonist ligand, at the same binding site of the repositioned drug candidate, would activate the opposite conformation of RCPG, inducing the integrity of the oncogenic reversion. The discovery of knowledge, could be done starting from other knowledge thus structured and stored, by using the methods of data mining, and in particular "the methods of bioguided excavation" The binding site of two ligands , reposioned drug ant its competitive antagonist(natural biomolecules , homologous by bioisosterism, in biogenetic relation// , is considered to be checkpoint , point of control of oncogenic transformation of the normal cell to cancerous cell.

This study clearly shows the constitutive activity of RCPGs involved in the neoplastic reaction, responsible for the complex phenotype of carcinoid tumors.

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