TNG917

TNG917 is an oral, clinical-grade, potent, and highly selective small molecule inhibitor of the histone methyltransferases EHMT1 (euchromatic histone lysine methyltransferase 1) and EHMT2 (euchromatic histone lysine methyltransferase 2). These enzymes catalyze mono- and di-methylation of lysine 9 on histone H3 (H3K9), leading to transcriptional repression of target genes. Inhibition of EHMT1/2 by TNG917 results in de-repression of gene promoters, upregulation of interferon-stimulated genes (ISGs), increased secretion of pro-inflammatory cytokines, and enhanced tumor immunogenicity. The drug is being developed for the treatment of immune cold tumors—tumors that are poorly infiltrated by immune cells and typically resistant to immunotherapy. Preclinical studies have demonstrated favorable pharmacodynamic and pharmacokinetic properties as well as efficacy in humanized and syngeneic mouse models. TNG917 is a first-in-pathway agent targeting epigenetic regulation to increase tumor sensitivity to immune attack[1][2][3].