Molecular Formula | C30H47N5O2 |
Molar Mass | 509.73 |
Density | 1.124±0.06 g/cm3(Predicted) |
Melting Point | 93-94℃ |
Boling Point | 610.2±55.0 °C(Predicted) |
pKa | 10.07±0.20(Predicted) |
Storage Condition | under inert gas (nitrogen or Argon) at 2–8 °C |
In vitro study | UNC0638 is an effective, selective, cell-permeable chemical probe for G9a and GLP, with a toxicity/functional ratio of less than 6 and a toxicity/functional ratio of greater than 100 compared to Bix01294. UNC0638 is a potent inhibitor of G9a and GLP, selective for a broad spectrum of epigenetic and non-epigenetic targets. UNC0638 is more than 10,000 times selective for SET7/9 (a H3K4 HMTase),SET8 (a H4K20 HMTase),PRMT3, and SUV39H2. In MDA-MB-231 cells, UNC0638 (48 h treatment) reduced H3K9me2 levels in a concentration-dependent manner with an IC50 of 81 nM. Treatment of various cell lines with UNC0638 resulted in a lower global reduction in H3K9me2 levels, which is consistent with the effect observed with shRNA to reduce G9a and GLP. UNC0638 significantly reduced the colony-forming ability of MCF7 cells, reduced the abundance of H3K9me2 in the promoter region of the endogenous gene regulated by G9a, and affected microRNAs. In mouse embryonic stem cells, UNC0638 reactivates a gene silenced by G9a and a reporter gene in a concentration-dependent manner, while not promoting differentiation. |
In vivo study | Metabolic and pharmacokinetic studies in mice have shown that UNC0638 has high in vivo clearance, short half-life, high volume distribution and low exposure. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.962 ml | 9.809 ml | 19.618 ml |
5 mM | 0.392 ml | 1.962 ml | 3.924 ml |
10 mM | 0.196 ml | 0.981 ml | 1.962 ml |
5 mM | 0.039 ml | 0.196 ml | 0.392 ml |
biological activity | UNC0638 is a potent and selective histone Lysine Methyltransferase (HMTase) inhibitor, g9a and GLP,IC50 |
Target | Value |
G9a (Cell-free assay) | <15 nM |
GLP (Cell-free assay) | 19 nM |