Biochem/physiol Actions

XIE62-1004 is a synthetic sequestosome-1 (p62, SQSTM1) ZZ domain ligand that induces disulfide bond-linked and PB1 domain-dependent p62 self-aggregation, leading to interaction with LC3 on autophagic membranes and p62/cargoes delivery (2.5-10 µM for 6-24 hrs in p62-expressing HeLa cultures). XIE62-1004 treatment (10 µM, 18 hrs) effectively reduces insoluble aggregates of transiently expressed mutant huntingtin (mHTT) constructs in HeLa (GFP-HDQ103) and PC12 (EGFP-HDQ74) trransfectants, as well as in wild-type, but not autophagy defective Atg5-/- MEFs (GFP-HDQ103).