Merck, SML3958-5MG, AZ505

Biochem/physiol Actions
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) that 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.