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Author
Parra Tejedor, Carles
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Abstract
CXCR4 is a G protein-coupled chemokine receptor that in recent years has been found to play a key role in tumor metastasis processes. This, coupled with the fact that it is one of the two receptors used by HIV to enter the host cell, make CXCR4 a prominent therapeutic target.
In the Pharmaceutical Chemistry Group of IQS they have developed several proposals for inhibitors for CXCR4 focused on the orthosteric binding site, where the natural ligand CXCL12 binds. However, based on the results of Dr. Albert Gibert's doctoral thesis, one of these inhibitors (called 3 {21}) appears to interact in a different place than expected. This fact raises the hypothesis of Allosterism in CXCR4.
In the present work, the possible binding of inhibitors in various al·lostèriques areas of the receptor is studied. In addition, several structural modifications are proposed to compound 3 {21} with the intention of improving the union in the al·lostèriques areas studied.
Finally, new families of compounds are proposed to be synthesized with the intention of improving the inhibition results of the receptor in two of its main binding sites through a study of interactions between the new inhibitor and the binding site.
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