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Merck
CN

SML2362

WRR139

≥98% (HPLC)

Synonym(s):

(S,E)-N-Isopentyl-4-phenyl-2-(3-tosylacrylamido)butanamide

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About This Item

Empirical Formula (Hill Notation):
C25H32N2O4S
CAS Number:
Molecular Weight:
456.60
NACRES:
NA.77
UNSPSC Code:
12352200
Assay:
≥98% (HPLC)
Form:
powder
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assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

2-8°C

Biochem/physiol Actions

NGLY1 (N-glycanase 1; PNGase) inhibitor that disrupts NGLY1-mediated NRF1 activation and potentiates carfilzomib cytotoxicity in cancer cultures.
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.


Storage Class

11 - Combustible Solids

WGK

WGK 3

Flash Point (°F)

Not applicable

Flash Point (°C)

Not applicable



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