ARP-47

ARP-47 is a novel Proteolysis Targeting Chimera (PROTAC) designed to selectively degrade Histone Deacetylase 1 (HDAC1) and Histone Deacetylase 2 (HDAC2). Developed by researchers at the University of Campinas (UNICAMP) and São Paulo State University (UNESP), it is being investigated for the treatment of beta-hemoglobinopathies, such as sickle cell disease and beta-thalassemia. The drug works by targeting HDAC1/2, which are key components of the NuRD and CoREST epigenetic complexes that repress the expression of the HBG1/2 genes. By degrading these enzymes, ARP-47 promotes an open chromatin conformation, thereby reactivating fetal hemoglobin (HbF) production. Preclinical studies in human CD34+ cells have shown that ARP-47 significantly increases the percentage of F-cells and gamma-globin protein levels at nanomolar concentrations without compromising cell viability or erythroid differentiation.