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AS-8351 has been used in a cocktail of nine small molecules used to efficiently induce cardiac reprogramming of human fibroblasts 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.

References:

1. N Cao et al. Science 2016 352:1216

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