Stemcell, 100-1653, UNC0224

Reprogram human somatic cells to pluripotent stem cells with UNC0224, a potent inhibitor of euchromatic histone methyltransferase 1 (EHMT1; IC50 = 39 nM) and EHMT2; IC50 = 15 nM. EHMT1 and EHMT2 can mono-, di-, and tri-methylate the lysine 9 residue of histone 3 (H3K9) to influence gene expression (Leenders et al. Bioorg Med Chem Lett, 2019; Liu et al. J Med Chem, 2009). EHMT1 and EHMT2 can heterodimerize to maintain H3K9 methylation in embryonic stem cells (Shinkai & Tachibana. Genes Dev, 2011; Zhang et al. Cell Rep, 2016). In several types of cancer, the overexpression of EHMT1 and EHMT2 is associated with metastasis, stemness, and therapy resistance. Further inhibiting H3K9 methylation through EHMT1/2 knockdown has been shown to have anti-tumor effects, inducing apoptosis, reducing cell migration, and suppressing tumor growth (Nachiyappan et al. FEBS J, 2022).

UNC0224 has been used for:

REPROGRAMMING

· Reprogram human somatic cells to pluripotent stem cells in combination with other small molecules (Guan et al. Nature, 2022).