[CAS NO. 1202055-32-0] NMS-P715
PRODUCTS SPECIFICATIONS [1202055-32-0]
DESCRIPTION [1202055-32-0]
Overview
| MDL | MFCD19443684 |
|---|---|
| Molecular Weight | 676.73 |
| Molecular Formula | C35H39F3N8O3 |
| SMILES | O=C(C1=NN(C)C2=C1CCC3=CN=C(NC4=CC=C(C(NC5CCN(C)CC5)=O)C=C4OC(F)(F)F)N=C23)NC6=C(CC)C=CC=C6CC |
Summary
NMS-P715 is a selective, ATP-competitive inhibitor of MPS1 , with an IC 50 of 182 nM.
IC50 & Target
|
Mps1 182 nM (IC 50 ) |
CK2 5.7 μM (IC 50 ) |
MELK 6.01 μM (IC 50 ) |
NEK6 6.02 μM (IC 50 ) |
In Vitro
NMS-P715 is a selective inhibitor of MPS1, with an IC 50 of 182 nM. NMS-P715 is highly specific for MPS1, with no other kinases inhibited below an IC 50 value of 5 μM and only 3 kinases inhibited below 10 μM (CK2, MELK, and NEK6). NMS-P715 promotes massive spindle assembly checkpoint (SAC) override with an EC 50 of 65 nM. NMS-P715 (1 μM) causes mitotic acceleration in U2OS cells overexpressing YFP-α-tubulin, induces aneuploidy and inhibits the proliferation of HCT116 cells. NMS-P715 (0.5, 1 μM) affects mitotic checkpoint complex (MCC) stability and cdc20 ubiquitylation [1] . NMS-P715 (1 μM) exhibits bypass of the spindle assembly checkpoint and apoptosis in pancreatic ductal adenocarcinoma (PDAC) cell lines. NMS-P715 (0-25 μM) also selectively inhibits growth of PDAC cells [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
NMS-P715 (10 mg/kg) exhibits an oral bioavailability of 37% and good pharmacokinetic properties in nude mice bearing subcutaneous implanted human tumor cell xenografts. NMS-P715 (90 mg/kg, p.o.) is well tolerated and cuases no signs of body weight loss or other overt toxicities in an A2780 ovary carcinoma xenograft model. NMS-P715 (100 mg/kg, p.o.) inhibits the tumor growth by appr 43% in the A375 melanoma xenograft model [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 2 mg/mL ( 2.96 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.4777 mL | 7.3885 mL | 14.7769 mL |
| 5 mM | --- | --- | --- |
| 10 mM | --- | --- | --- |
-
1.
Add each solvent one by one: 0.5% CMC/saline water
Solubility: 3.33 mg/mL (4.92 mM); Suspended solution; Need ultrasonic
References
- [1] Colombo R, et al. Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase. Cancer Res. 2010 Dec 15;70(24):10255-64.
- [2] Slee RB, et al. Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the mitotic MPS1 kinase inhibitor NMS-P715. Mol Cancer Ther. 2014 Feb;13(2):307-315.
