In vitro activity: AS8351 is a potent inhibitor of KDM5B (lysine-specific histone demethylase 5B) which plays an important role in maintaining cancer stem cells and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in cancer. AS8351 can induce and sustain active chromatin marks to facilitate the induction of cardiomyocyte-like cells. It induces reprogramming of human fetal lung fibroblasts into functional cardiomyocytes, in combination with CHIR 99021, A83-01, BIX 01294, SC1, Y-27632, OAC2, SU 16f and JNJ 10198409. Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells into specific homogeneous, functional cell types is challenging.

Kinase Assay: AS8351 affects epigenetic modifications by competing with α-ketoglutarate (α-KG) for chelating iron [Fe(II)] in certain epigenetic enzymes, such as the JmjC domain-containing histone demethylases (JmjC-KDMs) that require α-KG and iron as co-factors

Cell Assay: AS8351 is a KDM5B inhibitor, which can induce and sustain active chromatin marks to facilitate the induction of cardiomyocyte-like cells. AS8351 can induce and sustain active chromatin marks to facilitate the induction of cardiomyocyte-like cells. It induces reprogramming of human fetal lung fibroblasts into functional cardiomyocytes, in combination with CHIR 99021, A83-01, BIX 01294, SC1, Y-27632, OAC2, SU 16f and JNJ 10198409. Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells into specific homogeneous, functional cell types is challenging.