AZ505

AZ505 is a potent inhibitor of SMYD2, which plays an important role in epigenetic signalling. Inhibiition of SMYD2 also functions as an activator of the tumor suppressor proteins.

Potent and selective SMYD2 inhibitor in vitro and in vivo.

AZ505 is a potent and selective SET and MYND domain-containing protein SMYD2 inhibitor (IC50 = 120 nM) th at targets the substrate-binding site in a peptide substrate-competitive and cofactor SAM-uncompetitive manner, exhibiting no activity against lysine methyltransferases (KMTs) SMYD3, DOT1L, EZH2, GLP, G9A and SET7/9 (IC50 >83.3 μM). AZ505 downregulates p53 K370 monomethylation in U2OS cells (10h 10 μM) and delays cyst growth in early- (5 mg/kg/day i.p. from P7-P27) as well as later-stage (10 mg/kg via i.p. 3x per wk from P42-3.5 months, then 1x per wk from 3.5–6 months) Pkd1 conditional knockout mouse models in vivo.