Casein kinase II inhibitor IV is an effective small molecule inducer, which can be used to induce epidermal keratinocyte differentiation.

Treatment of human epidermal keratinocytes (NHEKs) with Casein Kinase II Inhibitor IV leads to an increase in the early differentiation markers keratins 1 and 10 at 48 h. Increased levels of IVL and TGM are observed in cells treated with Casein Kinase II Inhibitor IV at 72 h and persisted at 96 h. In addition, treated with Casein Kinase II Inhibitor IV expresses loricrin, a terminal differentiation marker, at later time points. Similar results are observed by messenger RNA (mRNA) expression analysis of NHEKs treated with Casein Kinase II Inhibitor IV. At early time points (12 and 24 h), treatment with Casein Kinase II Inhibitor IV leads to the upregulation of keratinocyte early differentiation marker genes, including keratin 1 (5.4-fold) and keratin 10 (5.4-fold). Terminal differentiation marker genes, including IVL (1.8-fold), TGM 1 (4.8-fold), loricrin (3.3-fold), and filaggrin (5.6-fold), are upregulated at late time points (36 and 48 h).