Thesis defence of Xavier Jalencas "Chemoisosterism and its impact on drug polypharmacology"

On September 17th, Xavier Jalencas, member of the Systems Pharmacology Group of GRIB (IMIM-UPF) will defend his thesis at 12.00 at the PRBB Auditorium. You are all invited to this event.


In medicinal chemistry, two chemical fragments are considered bioisosteric if they bind to the same protein environment. Accordingly, looking at the same players from an opposite perspective, two protein environments can be considered chemoisosteric if they interact with the same chemical fragment. In this respect, this Thesis introduces the term chemoisosterism, which represents a new concept in drug discovery.

Currently available crystal structures for protein-ligand complexes constitute a basis for the identification of chemoisosteric protein environments, of great utility for the construction of focused fragment chemical libraries. Under the premise that similar protein environments will probably bind to similar fragments, a novel approach to assess protein environment similarities is introduced and used to predict new chemoisosteric relationships. Examples of the potential applicability of chemoisosterism in fragment-based drug discovery are provided. The implications of chemoisosterism for drug polypharmacology are explored, leading to the speculation that the levels of polypharmacology observed in current drugs may just be a latent signature of the exploitation of chemoisosterism during evolution.

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