1 research outputs found
Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2
Protein
lysine methyltransferases have recently emerged as a new target class
for the development of inhibitors that modulate gene transcription
or signaling pathways. SET and MYND domain containing protein 2 (SMYD2)
is a catalytic SET domain containing methyltransferase reported to
monomethylate lysine residues on histone and nonhistone proteins.
Although several studies have uncovered an important role of SMYD2
in promoting cancer by protein methylation, the biology of SMYD2 is
far from being fully understood. Utilization of highly potent and
selective chemical probes for target validation has emerged as a concept
which circumvents possible limitations of knockdown experiments and,
in particular, could result in an improved exploration of drug targets
with a complex underlying biology. Here, we report the development
of a potent, selective, and cell-active, substrate-competitive inhibitor
of SMYD2, which is the first reported inhibitor suitable for in vivo
target validation studies in rodents