KMI169 (KMI-169) is a potent and selective lysine methyltransferase 9 (KMT9) inhibitor with ITC Kd of 25 nM and enzymatic IC50 of 50 nM.
KMI169 displays high selectivity for KMT9 against a large panel of SET domain- or Rossmann fold-containing methyltransferases as well as protein kinases.
KMI169 dispalys a linear dependence upon increasing SAM or substrate concentrations corroborating a competitive inhibition mode.
KMI169 demonstrates cell membrane permeability and cellular target engagement, impairs tumour cell proliferation with GI50 of 120 nM in PC-3M cells, as well as in other prostate, bladder, lung, and colon tumour cells.
KMI169 also impairs proliferation of castration- and enzalutamide-resistant prostate cancer cell lines such as PC-3M, DU145, LNCaP-abl, and LNCaP-abl EnzaR.
KMI169 affects expression of genes involved in cell cycle regulation, including MYB proto-oncogene (MYB), aurora kinase B (AURKB), forkhead box A2 (FOXA2), cyclin dependent kinase 2 (CDK2), baculoviral iap repeat containing 5 (BIRC5), E2F transcription factor 1 (E2F1), E2F transcription factor 8 (E2F8), cell division cycle 6 (CDC6), and DNA ligase 1 (LIG1).
KMI169 is a suitable tool to study cellular KMT9 functions.