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Products are for research use only. Not for human use. We do not sell to patients.
(NMS873; NMS 873)
NMS-873 Chemical Structure
|Product name: NMS-873|
|Cat. No.: HY-15713|
NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with IC50 value of 20 nM (Wild Type, 1 mM ATP).
IC50 value: 20 nM (Wild Type VCP, 1 mM ATP)
in vitro: In standard assay conditions, NMS-873 had an IC50 of 30 nM, which was unchanged at saturating ATP concentration. NMS-862, which has micromolar biochemical potency, did not have measurable antiproliferative activity (IC50 >10 μM), whereas the nanomolar activity of NMS-873 translated into a submicromolar antiproliferative IC50 in HCT116 (0.4 μM) and HeLa (0.7 μM)
cells. We measured IC50 values in the range of 0.08 μM to 2 μM for NMS-873 in a panel of tumor cell lines that suggested potent but somehow selective inhibitor activity in different tumor cell lines .
|M.Wt||520.67||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO: ≤ 20.5 mg/mL
|1 mg||5 mg||10 mg|
|1 mM||1.9206 mL||9.6030 mL||19.2060 mL|
|5 mM||0.3841 mL||1.9206 mL||3.8412 mL|
|10 mM||0.1921 mL||0.9603 mL||1.9206 mL|
. Paola Magnaghi, Roberto D'Alessio, Barbara Valsasina, et al. Covalent and allosteric inhibitors of the ATPATP ase VCP/p97 induce cancer cell death. Nat Chem Biol. 2013 Jul 28. doi: 10.1038/nchembio.1313.
VCP (also known as p97 or Cdc48p in yeast) is an AAA(+) ATPase regulating endoplasmic reticulum-associated degradation. After high-throughput screening, we developed compounds that inhibit VCP via different mechanisms, including covalent modification of an active site cysteine and a new allosteric mechanism. Using photoaffinity labeling, structural analysis and mutagenesis, we mapped the binding site of allosteric inhibitors to a region spanning the D1 and D2 domains of adjacent protomers encompassing elements important for nucleotide-state sensing and ATP hydrolysis. These compounds induced an increased affinity for nucleotides. Interference with nucleotide turnover in individual subunits and distortion of interprotomer communication cooperated to impair VCP enzymatic activity. Chemical expansion of this allosteric class identified NMS-873, the most potent and specific VCP inhibitor described to date, which activated the unfolded protein response, interfered with autophagy and induced cancer cell death. The consistent pattern of cancer cell killing by covalent and allosteric inhibitors provided critical validation of VCP as a cancer target.
CB-5083 is a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor with IC50 of 11nM.
DBeQ(JRF-12) is a selective, potent, reversible, and ATP-competitive p97 inhibitor with IC50 of 1.5 (mu)M.
ML240 is a selective, ATP-competitive p97 inhibitor with IC50 values of 100 nM.
NMS-859 is a potent and specific small molecule covalent inhibitor of the ATPase VCP/p97 (IC50 ~0.37 (mu)M), identified by high-throughput screening.