UNC0379 (trifluoroacetate)

Uses

UNC0379 TFA is a selective, substrate-competitive inhibitor of lysine methyltransferase SETD8 (KMT5A) with an IC50 of 7.3 μM, KD value of 18.3 μM. UNC0379 TFA can be used in the research of inflammation and cancers, such as pulmonary fibrosis, ovarian cancer, neuroblastoma[1][2][3].

Biological Activity

SETD8 expression is observed in cancers such as bladder cancer, chronic myelogenous leukemia, hepatocellular carcinoma, non‐small‐cell lung carcinoma, prostate cancer, small‐cell lung carcinoma. Therefore inhibition of SETD8 (SET‐domain containing protein) by UNC0379 might prevent the progression of cancer.', 'UNC0379 is the first substrate-competitive inhibitor of the lysine methyltransferase SETD8, the only known methyltransferase th at catalyzes monomethylation of histone H4 lysine 20 (H4K20). HK420 methylation has been implicated in the regulation of a variety of biological processes including the DNA damage response. UNC0379 is selective for SETD8 over 15 other methyltransferases, with an IC50 value of 7.3 μM for SETD8 compared to IC50 vlaues over 100 μM for other methyltransferases.

in vivo

References

[1] Ma A, et al. Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8. J Med Chem. 2014 Aug 14;57(15):6822-33. DOI:10.1021/jm500871s
[2] Miku Wada, et al. Epigenetic Modifier SETD8 as a Therapeutic Target for High-Grade Serous Ovarian Cancer. Biomolecules. 2020 Dec 16;10(12):1686. DOI:10.3390/biom10121686
[3] Keita Ugai, et al. Inhibition of the SET8 Pathway Ameliorates Lung Fibrosis Even Through Fibroblast Dedifferentiation. Front Mol Biosci. 2020 Aug 5;7:192. DOI:10.3389/fmolb.2020.00192