2-Chloro-N,N-diethyl-5-[[4-[2-[4-[[(MethylaMino)carbonyl]aMino]phenyl]-4-pyridinyl]-2-pyriMidinyl]aMino]benzenesulfonaMide

2-Chloro-N,N-diethyl-5-[[4-[2-[4-[[(MethylaMino)carbonyl]aMino]phenyl]-4-pyridinyl]-2-pyriMidinyl]aMino]benzenesulfonaMide Property

Density 

1.353±0.06 g/cm3(Predicted)

storage temp. 

4°C, away from moisture and light

solubility 

DMSO: 2mg/mL, clear

form 

Solid

pka

14.00±0.46(Predicted)

color 

White to yellow

Hazard and Precautionary Statements (GHS)

2-Chloro-N,N-diethyl-5-[[4-[2-[4-[[(MethylaMino)carbonyl]aMino]phenyl]-4-pyridinyl]-2-pyriMidinyl]aMino]benzenesulfonaMide Chemical Properties,Usage,Production

Uses

2-Chloro-N,N-diethyl-5-[[4-[2-[4-[[(methylamino)carbonyl]amino]phenyl]-4-pyridinyl]-2-pyrimidinyl]amino]benzenesulfonamide are pyrimidine derivatives as hSMG-1 inhibitors.

Biological Activity

Potent and selective SMG-1 (hSMG-1; SMG1) kinase inhibitor th at blocks nonsense-mediated decay (NMD).


SMG1i is a potent and selective SMG-1 kinase inhibitor (hSMG-1 IC50 = 110 pM) with much reduced potency against mTOR, PI3Kα/γ and CDK1/2 (IC50 = 50 nM, 92/60 nM, 32/7.1 μM, respectively). SMG1i selectively downregulates MDA361 cellular phosphorylation of UPF1 (0.3 -1 μM), but not th at of mTOR or AKT substrates (p70s6 K and PI3K). Nonsense-mediated decay (NMD) inhibition by SMG1i (1 μM) is shown to synergize with premature termination codons (PTCs) readthrough agents (G418, gentamicin, and paromomycin) in promoting the expression of CFTR protein in murine cells carrying Cftr G542X nonsense mutation.

IC 50

hSMG-1: 0.11 nM (IC₅₀); mTOR: 50 nM (IC₅₀); PI3Kγ: 60 nM (IC₅₀); PI3Kα: 92 nM (IC₅₀); GSKα: 260 (IC₅₀); GSKβ: 330 (IC₅₀); CDK2: 7.1 μM (IC₅₀); CDK1: 32 μM (IC₅₀)