1202055-34-2

1202055-34-2 structure

1202055-34-2 structure

Name: NMS-P715
Chemical Name: N-(2,6-diethylphenyl)-8-({2-methoxy-4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
CAS Number: 1202055-34-2
Molecular Formula: C₃₅H₄₂N₈O₃
Molecular Weight: 622.760
Catalog: Signaling Pathways Cell Cycle/DNA Damage Mps1
Create Date: 2017-02-09 04:05:15
Modify Date: 2024-01-10 07:35:42
NMS-P715 analog is an inhibitor of MPS1, with an IC50 of 84 nM.

Name	N-(2,6-diethylphenyl)-8-({2-methoxy-4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Synonyms	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)

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.

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