Synonyms: (S,E)-N-Isopentyl-4-phenyl-2-(3-tosylacrylamido)butanamide
Molecular Formula: C25H32N2O4S
Molecular Weight: 456.6
Linear Structural Formula: C25H32N2O4S
Purity: >=98% (HPLC)
Storage: 2-8C
Biochem Physiol Actions: WRR139 is a peptidyl vinyl sulfone that inhibits NGLY1 (N-glycanase 1; PNGase; Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase) de-N-glycosylation activity in cell-free enzymatic assays (IC50 <10 μM; 3.75 rhNGLY1 wtih 1.7 μg S-alkylated RNase B as substrate) and in cultures (IC50 = 5.5 μM in ddVenus reporter K562 cells co-treated with 1 μM proteasome inhibitor carfilzomib). WRR139 disrupts NGLY1-mediated nuclear respiratory factor 1 (NRF1) processing/activation. WRR139 (1 μM) is shown to potentiate the cytotoxicity of proteasome inhibitor carfilzomib (1-100 nM) in multiple myeloma (MM; U266 & H929), T-cell acute lymphoblastic leukemia (T-ALL; Jurkat), and HeLa cultures, but not in NGLY1-knockdown HeLa cells. Note: concentrations below 10 μM is generally recommended for culture treatment to avoid off-target activity against caspases.