orally available fetal hemoglobin inducer
oral induction of fetal hemoglobal in cyno
from phenotypic screen and ADME opt.
Bioorg. Med. Chem. Lett., Jul. 24, 2020
Daiichi-Sankyo, Tokyo, JP / Asubio
“compound 18” is an oral inducer of fetal hemoglobin (HbF) intended to treat anemias such as sickle cell disease and beta-thalassemia. The authors identified a weak hit (>10 uM) from a high-throughput phenotypic screen using human umbilical cord blood-derived erythroid progenitor cells. Optimization led to the azaspiro[3.3]heptane-containing compound 18, which demonstrated significant HbF induction in cynos without significant safety issues. The mechanism of action is unclear and will hopefully disclosed in the future.