CB-5339

CB-5339 is an inhibitor of the AAA-ATPase p97, also known as valosin-containing protein (VCP, IC50 = 9 nM), and a derivative of CB-5083 (Cay-19311). It inhibits phosphodiesterase 6C (PDE6C) and accumulates in rat retina to a lesser extent than CB-5083. CB-5339 inhibits the growth of 16 primary acute myeloid leukemia (AML) cell lines (median IC50 = 375 nM) and induces polyubiquitin protein accumulation and endoplasmic reticulum (ER) stress in MV4-11 AML cells. It decreases tumor cell bone marrow infiltration and increases survival in an MLL-AF9-driven patient-derived xenograft (PDX) mouse model of AML at 90 mg/kg.. SMILES: CC1=CC2=C(C=CC=C2C(N)=O)N1C3=NC(NCC4=CC=CC=C4)=C5C(N3)=NCCC5. InChi Code: InChI=1S/C24H24N6O/c1-15-13-19-17(21(25)31)9-5-11-20(19)30(15)24-28-22-18(10-6-12-26-22)23(29-24)27-14-16-7-3-2-4-8-16/h2-5,7-9,11,13H,6,10,12,14H2,1H3,(H2,25,31)(H2,26,27,28,29). InChi Key: XDHFSLWWYBVSLN-UHFFFAOYSA-N