AS-8351 | KDM5B histone demethylase inhibitor

AS-8351 (796-42-9) has been used in a cocktail of nine small molecules used to efficiently induce cardiac reprogramming of human fibroblasts.¹ It is believed that AS-8351 exerts its effects by modulating the activity of the JmjC domain-containing histone demethylases (JmjC-KDM). Thus each of the 22 genes in the JmjC-KDM family was abrogated using small hairpin RNAs which showed that only knocking down KDM5B (or using another KDM5B inhibitor such as PBIT) could phenocopy AS-8351 in generating cardiomyocytes. This strongly suggests that KDM5B is the target of AS-8351.¹

References/Citations

1) Cao et al. (2016), Conversion of human fibroblasts into functional cardiomyocytes by small molecules; Science, 352 1216