New compounds raise hopes for CF patients
The chloride ion channel 'responsible' for CF pathology has been termed the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Alterations in CFTR function are attributed to specific mutations, which give rise to ill-processed CFTR structures, unable to properly carry out their designated functions. Project partner, Université de Poitiers, looked to isolate new compounds that could alter the activity of CFTR and thus somehow correct its dysfunction. One of the starting points was the MPB molecule. A detailed structure-activity relationship (SAR) study was carried out in order to determine which structural elements are linked to specific functional characteristics. A series of MPB-based derivatives was tested and a number were found to fulfil the screening criteria as CFTR activators. The University is also carrying out further studies in order to determine the effects of these compounds on cell populations. Furthermore, the SAR studies revealed valuable information regarding the importance of structural chemical groups on the function of MPB and hence its derivatives. The University has isolated a specific lead termed MPB-90, with increased potency compared to other derivatives. Further research is now needed to fully evaluate MPB-90 as well as other members of the same series of compounds. Pharmaceutical companies active in the field of CF are likely to benefit from the emerging know-how from the CF-PRONET project and might be in a position to further this line of research towards clinical trials.
