Naphthalene-containing Selective Inhibitors of BMP type 1 Receptors for the Treatment of Fibrodysplasia Ossificans Progressiva

This technology includes the use of a new class of molecules (nanomolar ALK2 inhibitor) to impede bone morphogenetic proteins (BMP) signaling for the treatment of Fibrodysplasia ossificans progressiva (FOP). FOP is a rare disease, characterized by malformation of the great (big) toes during embryonic development. Individuals with FOP have identical heterozygous activating mutation (R206H) in the gene encoding ACRV1 (also known as ALK2), a BMP type 1 receptor. This compound was created by replacing a quinoline moeity with a naphthalene moeity which gave rise to a class of molecules that are not susceptible to aldehyde oxidase (AO) metabolism, a major pathway for quinoline-containing molecules. Elimination of this metabolic pathway can have major benefits, such as increased systemic exposure, prevention of potential toxic effects of quinoline metabolites, and avoiding inter-subject variability based on AO polymorphism.