NMS-873 is an allosteric and specific p97 inhibitor with IC50 of 30 nM. NMS-873 has antiproliferative effect on a panel of tumor cell lines with IC50 values in the range of 0.08 μM to 2 μM. For HCT116 and HeLa cells, the IC50 values are 0.4 μM and 0.7 μM, respectively. NMS-873 reduces VCP sensitivity to trypsin digestion, preventing degradation of the linker-D2 domain.
Nature. 2017 Dec 6.
Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
NMS-873 purchased from AbMole
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Source | Nature (2017). Figure 6. NMS873 (Abmole Bioscience) |
| Method | Western blot | |
| Cell Lines | NIH3T3 cells | |
| Concentrations | 5 μM | |
| Incubation Time | 3 h | |
| Results | In contrast to treatment with NMS873, CuET had no effect on p97 ATPase activity |
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Source | Nature (2017). Figure 4. NMS873 (Abmole Bioscience) |
| Method | Western blot | |
| Cell Lines | NIH3T3 cells | |
| Concentrations | 5 μM | |
| Incubation Time | 3 h | |
| Results | We confirmed UPR in cells treated with CuET or NMS873 by detecting increased markers of UPR induction, including the spliced form of XBP1s, ATF4 and phosphorylated (p-) eIF2α33 |
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Source | Nature (2017). Figure 2. NMS873 (Abmole Bioscience) |
| Method | colony-formation assay | |
| Cell Lines | U2OS cell | |
| Concentrations | 10 μM | |
| Incubation Time | 16 h | |
| Results | Furthermore, consistent with cleavage of the 120-kDa species of the endoplasmic reticulum-tethered transcription factor NRF1 into an active 110-kDa form being a p97-dependent process30, appearance of the cleaved NRF1 form was inhibited by both CuET and NMS873 |
| Molecular Weight | 520.67 |
| Formula | C27H28N4O3S2 |
| CAS Number | 1418013-75-8 |
| Solubility (25°C) | DMSO 30 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related p97 Products |
|---|
| CB-5339
CB-5339 is a potent p97 inhibitor with an IC50 <30 nM (WO2015109285A1, compound FF07). |
| CB-5083
CB-5083 is a first-in-class, potent and selective, orally bioavailable inhibitor of the p97 AAA ATPase/VCP. CB-5083 selectively inhibits p97 through its D2 site with the IC50 of 11 nM. |
| DBeQ
DBeQ is a selective, potent, reversible, and ATP-competitive p97 inhibitor with IC50 of 1.5 μM. |
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