PTX80 is an antagonist of p62 (IC50 = 31.18 nM for the human receptor).1 It decreases the soluble fraction of p62 in MM.1S multiple myeloma cells when used at a concentration of 1.5 ?M. PTX80 (200 nM) increases the levels of polyubiquitinated proteins in MM.1S cells. It induces apoptosis in MM.1S cells when used at a concentration of 100 nM. PTX80 (50-400 nM) decreases the survival of CD138+ cells, but not CD138- cells, in primary plasma cells derived from patients with multiple myeloma. It reduces the viability of tumor tissue samples isolated from ten patient-derived xenograft (PDX) mouse models of colorectal cancer (IC50s = 113-1,220 nM). In vivo, PTX80 (8 or 12 mg/kg twice per week) reduces tumor volume in an HCT116 colorectal cancer mouse xenograft model.
References:
[1]. Kalid, O., Gotliv, I., Levy-Apter, E., et al.PTX80, a novel compound targeting the autophagy receptor p62/SQSTM1 for treatment of cancerChem. Biol. Drug Des.100(5)623-638(2022).