Synonym
NMS873, NMS-873, NMS 873
IUPAC/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.
InChi Key
UJGTUKMAJVCBIS-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H28N4O3S2/c1-19-16-22(11-14-25(19)20-9-12-24(13-10-20)36(2,32)33)34-18-26-29-30-27(35-23-7-3-4-8-23)31(26)21-6-5-15-28-17-21/h5-6,9-17,23H,3-4,7-8,18H2,1-2H3
SMILES Code
O=S(C1=CC=C(C2=CC=C(OCC3=NN=C(SC4CCCC4)N3C5=CC=CN=C5)C=C2C)C=C1)(C)=O
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with an IC50 value of 30 nM.
In vitro activity:
As NMS-873 is a host-targeting antiviral, it is important to rule out the possibility that the antiviral activity of NMS-873 might be celltype dependent. For this, the antiviral activity of NMS-873 was tested in two human lung epithelial cell lines, A549 and BEAS-2B, as well as in human lung epithelial primary cells (Fig. 3). When A549 cells were infected with A/WSN/33 (H1N1) virus at a MOI of 0.01, NMS-873 significantly inhibited the viral replication at both 12 h p.i. and 24 h p.i. in a dose-dependent manner (Fig. 3D). The viral titer was significantly reduced 1.3–1.4 and 2.2–3.1 log10 units by 2 μM and 3 μM of NMS-873, respectively, while 2.1–2.5 log10 units of reduction was observed for oseltamivir (Fig. 3D). Of note, the highest drug concentration tested (3 μM) was not cytotoxic to A549 cells (Fig. 3A). For BEAS-2B and primary cells, a similar potent antiviral effect was observed (Fig. 3E and.3F). Taken together, these results confirmed the antiviral activity of NMS-873 in both human cell lines and primary cells and thus ruled out the possibility that the antiviral activity of NMS-873 is cell-type dependent. In this study, it was reported that NMS-873, a host p97 inhibitor, inhibits both influenza A and B viruses with low-nanomolar efficacy (Fig. 1 and Table 1). In conclusion, the broad-spectrum antiviral activity and novel mechanism of action of NMS-873 render it a promising antiviral drug candidate
Reference: Eur J Pharm Sci. 2019 May 15; 133: 86–94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482079/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.0 |
38.40 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
520.67
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Zhang J, Hu Y, Hau R, Musharrafieh R, Ma C, Zhou X, Chen Y, Wang J. Identification of NMS-873, an allosteric and specific p97 inhibitor, as a broad antiviral against both influenza A and B viruses. Eur J Pharm Sci. 2019 May 15;133:86-94. doi: 10.1016/j.ejps.2019.03.020. Epub 2019 Mar 28. PMID: 30930289; PMCID: PMC6482079. 2. Bouwer MF, Hamilton KE, Jonker PB, Kuiper SR, Louters LL, Looyenga BD. NMS-873 functions as a dual inhibitor of mitochondrial oxidative phosphorylation. Biochimie. 2021 Jun;185:33-42. doi: 10.1016/j.biochi.2021.03.004. Epub 2021 Mar 13. PMID: 33727138; PMCID: PMC8119374.
In vitro protocol:
1. Zhang J, Hu Y, Hau R, Musharrafieh R, Ma C, Zhou X, Chen Y, Wang J. Identification of NMS-873, an allosteric and specific p97 inhibitor, as a broad antiviral against both influenza A and B viruses. Eur J Pharm Sci. 2019 May 15;133:86-94. doi: 10.1016/j.ejps.2019.03.020. Epub 2019 Mar 28. PMID: 30930289; PMCID: PMC6482079. 2. Bouwer MF, Hamilton KE, Jonker PB, Kuiper SR, Louters LL, Looyenga BD. NMS-873 functions as a dual inhibitor of mitochondrial oxidative phosphorylation. Biochimie. 2021 Jun;185:33-42. doi: 10.1016/j.biochi.2021.03.004. Epub 2021 Mar 13. PMID: 33727138; PMCID: PMC8119374.
1: Magnaghi P, D'Alessio R, Valsasina B, Avanzi N, Rizzi S, Asa D, Gasparri F, Cozzi L, Cucchi U, Orrenius C, Polucci P, Ballinari D, Perrera C, Leone A, Cervi G, Casale E, Xiao Y, Wong C, Anderson DJ, Galvani A, Donati D, O'Brien T, Jackson PK, Isacchi A. Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death. Nat Chem Biol. 2013 Sep;9(9):548-56. doi: 10.1038/nchembio.1313. Epub 2013 Jul 28. PubMed PMID: 23892893.
