SML2362
WRR139
≥98% (HPLC)
Synonym(s):
(S,E)-N-Isopentyl-4-phenyl-2-(3-tosylacrylamido)butanamide
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5 MG
$203.00
25 MG
$610.00
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5 MG
$203.00
25 MG
$610.00
About This Item
Empirical Formula (Hill Notation):
C25H32N2O4S
CAS Number:
Molecular Weight:
456.60
UNSPSC Code:
12352200
NACRES:
NA.77
Recommended Products
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_germany
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
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Frederick M Tomlin et al.
ACS central science, 3(11), 1143-1155 (2017-12-05)
Proteasome inhibitors are used to treat blood cancers such as multiple myeloma (MM) and mantle cell lymphoma. The efficacy of these drugs is frequently undermined by acquired resistance. One mechanism of proteasome inhibitor resistance may involve the transcription factor Nuclear
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