molecules of the month

“compound 18”

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

Structure of compound 18
1 min read

“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.

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