Discovery of SDS-347 as a specific peptide competitive inhibitor of G9a with promising anti-cancer potential.

Background: G9a is a histone H3K9 methyltransferase enzyme found highly upregulated in many cancers. H3 binds to the rigid I-SET domain and the cofactor, S-adenosyl methionine, binds to the flexible post-SET domain of G9a. Inhibition of G9a is known to inhibit the growth of cancer cell-lines.

Targeting EHMT2/ G9a for cancer therapy: Progress and perspective.

Euchromatic histone lysine methyltransferase-2, also known as G9a, is a ubiquitously expressed SET domain-containing histone lysine methyltransferase linked with both facultative and constitutive heterochromatin formation and transcriptional repression. It is an essential developmental gene and reported to play role in embryonic development, establishment of proviral silencing in ES cells, tumor cell growth, metastasis, T-cell immune response, cocaine induced neural plasticity and cognition and adaptive behavior. It is mainly responsible for carrying out mono, di and tri methylation of histone H3K9 in euchromatin.

Rottlerin is a pan phosphodiesterase inhibitor and can induce neurodifferentiation in IMR-32 human neuroblastoma cells.

Phosphodiesterases are promising targets for pharmacological intervention against various diseases. There are already inhibitors of PDE3, PDE4 and PDE5 as approved drugs. However there is an unmet need to discover new chemical scaffolds as PDE inhibitors.