| Molecular Weight: | 520.67 |
| Formula: | C27H28N4O3S2 |
| Purity: | ≥98% |
| CAS#: | 1418013-75-8 |
| Solubility: | DMSO up to 100 mM |
| Chemical Name: | 3-(3-(cyclopentylthio)-5-(((2-methyl-4'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl)oxy)methyl)-4H-1,2,4-triazol-4-yl)pyridine |
| Storage: | Powder:4oC 1 year. DMSO:4oC3 month;-20oC 1 year. |
Biological Activity:
NMS-873 is a potent and specific small molecule allosteric inhibitor of the ATPase VCP/p97 (IC50 ~0.03 µM), identified by a high-throughput screening. It is very selective (IC50 >10 μM) against all of the AAA ATPases, HSP90 or the 53 kinases tested. Using photo-affinity labeling, structural analysis and mutagenesis, the binding site of NMS-873 was found to be a region spanning the D1 and D2 domains of adjacent protomers encompassing elements important for nucleotide-state sensing and ATP hydrolysis. NMS-873 activated the unfolded protein response, interfered with autophagy, and induced cancer cell death. NMS-873 provided critical validation of VCP as a cancer target, and it raises the possibility that targeting VCP might prevent proteasome inhibitor–resistant tumors from escaping through the aggresome-autophagy pathways and cause them to collapse under the high load of unfolded proteins.
How to Use:
- In vitro: NMS-873 was used at 2.5-10 µM final concentration in various in vitro assays.
- In vivo: n/a
Reference:
- 1. Magnaghi P, et al. Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death. (2013) Nat Chem Biol. 9(9):548-56
NMS-873_spec.pdf- NMS-873_MSDS.pdf
Products are for research use only. Not for human use.
