molecules of the month

Induction of fetal hemoglobin expression by a PRC-targeting small molecule. Pociredir (FTX-6058) is an oral, allosteric polycomb repressive complex 2 (PRC2) inhibitor that binds embryonic ectoderm development protein (EED) within this complex, ultimately boosting fetal hemoglobin (HbF) expression. Increasing HbF levels has been shown to mitigate the mortality and morbidity risks of Sickle Cell Disease (SCD), which are caused by mutations in the adult hemoglobin HBB gene. As a small molecule treatment, this macrocyclic azolopyridine distinguishes itself in a therapeutic area dominated by gene-correction candidates. For chemists, it is a notable example of a 9-membered macrocycle with relatively high ring strain (~15.5 kcal/mol) that has entered clinical development.  The first clinical EED1 inhibitor for sickle cell disease. In recent years,…