NMS-P715

Names

[ CAS No. ]:
1202055-34-2

[ Name ]:
NMS-P715

[Synonym ]:
NMS P715 analog
NMS-P715 analog
N-(2,6-Diethylphenyl)-8-({2-methoxy-4-[(1-methyl-4-piperidinyl)carbamoyl]phenyl}amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
NMS-P 715 analog
1H-Pyrazolo[4,3-h]quinazoline-3-carboxamide, N-(2,6-diethylphenyl)-4,5-dihydro-8-[[2-methoxy-4-[[(1-methyl-4-piperidinyl)amino]carbonyl]phenyl]amino]-1-methyl-
NMS-P715
NMS-P715 (analog)

Biological Activity

[Description]:

NMS-P715 analog is an inhibitor of MPS1, with an IC50 of 84 nM.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Mps1

Signaling Pathways >> Cytoskeleton >> Mps1

Research Areas >> Cancer

[Target]

MPS1:84 nM (IC50)

PLK1:237 nM (IC50)

Aur-A:1450 nM (IC50)

[In Vitro]

NMS-P715 analog (Compound 14) is an inhibitor of MPS1, with an IC50 of 84 nM; also less active on Aur-A, CDK2/A and PLK1 (IC50, 1.45, >10, 0.237 μM). In addition, NMS-P715 analog shows inhibitory effect on human tumor cell line (A2780) with an IC50 of 150 nM.

[Kinase Assay]

The potency of the compounds (NMS-P715 analog, etc.) towards MPS1, Aur-A, CDK2/A, and PLK1 is determined using either a strong anion exchanger based assay or P81 Multiscreen plate, both based on the specific measurement of radioactive phospho-transfer to the substrate. For each enzyme, the absolute Km values for ATP and the specific substrate are initially determined and each assay is then run at optimized [ATP] (2•αKm) and [substrate] (5•Km) concentrations. These conditions enabled direct comparison of IC50 values across the different kinases to evaluate the selectivity profile. Activity is measured using 5 nM of MPS1 recombinant protein in 50 mM HEPES pH 7.5, 2.5 mM MgCl2, 1 mM MnCl2, 1 mM DTT, 3 μM NaVO3, 2 mM β-glycerophosphate, 0.2 mg/mL BSA, 200 μM P38-βtide substrate-peptide (KRQADEEMTGYVATRWYRAE) and 8 μM ATP with 1.5 nM 33P-γ-ATP[1].

[Cell Assay]

A2780 ovarian carcinoma cells (ECACC) cultured in RPMI medium, supplemented with 10% fetal calf serum (FCS) and 2 mM L-Glutamine are seeded in 384 well-plates and treated with compounds (NMS-P715 analog, etc.) dissolved in 0.1% DMSO 24 hours after seeding. The cells are incubated at 37°C and 5% CO2 and after 72 hours the plates are processed using CellTiter-Glo assay. Inhibitory activity is evaluated comparing treated versus control data using Assay Explorer software. IC50 of proliferation is calculated using sigmoidal interpolation curve fitting[1].

[References]

[1]. Caldarelli M, et al. Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors. Bioorg Med Chem Lett. 2011 Aug 1;21(15):4507-11.

[Related Small Molecules]

CFI402257 | BAY1217389 | BAY 1161909 | NMS-P715 | AZ 3146 | BOS172722 | MPI-0479605 | Mps1-IN-1 | Mps1-IN-2 | Mps1-IN-3 | CCT251455

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Molecular Formula ]:
C₃₅H₄₂N₈O₃

[ Molecular Weight ]:
622.760

[ Exact Mass ]:
622.338013

[ PSA ]:
126.30000

[ LogP ]:
3.69

[ Index of Refraction ]:
1.676

Related Compounds

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