NIK SMI1

• CAT Number: I019822
• CAS Number: 1660114-31-7
• Molecular Formula: C20H19N3O4
• Molecular Weight: 365.38
• Purity: ≥95%
• Synonyms: 6-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-4-methoxypyridine-2-carboxamide
• InChI: InChI=1S/C20H19N3O4/c1-23-9-8-20(26,19(23)25)7-6-13-4-3-5-14(10-13)16-11-15(27-2)12-17(22-16)18(21)24/h3-5,10-12,26H,8-9H2,1-2H3,(H2,21,24)/t20-/m0/s1
• InChIKey: LQSHXYHWYGKAMX-FQEVSTJZSA-N
• SMILES: CN1CCC(C1=O)(C#CC2=CC(=CC=C2)C3=NC(=CC(=C3)OC)C(=O)N)O

NIK SMI1 is a potent, selective NF-κB inducing kinase (NIK) inhibitor, which inhibits NIK-catalyzed hydrolysis of ATP to ADP with IC50 of 0.23±0.17 nM. NIK SMI1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
NIK SMI1 (Compound 4f) inhibits NIK-catalyzed hydrolysis of ATP to ADP (fluorescence polarization, FP) with an IC50 of 0.23±0.17 nM. NIK SMI1 inhibits the expression of NIK SMI1 response elementregulated firefly luciferase reporter gene in HEK293 cells with an IC50 of 34±6 nM. Consistent with expectations for a NIK inhibitor, NIK SMI1 is shown to inhibit nuclear translocation of p52 (RelB) (IC50=70 nM). NIK SMI1 inhibits BAFF-induced B cell (mouse) survival in vitro with an IC50 of 373±64 nM[1].
C57BL/6 mice are treated twice daily for 7 days with orally administered NIK SMI1 or with three injections of recombinant BAFF receptor fusion protein (Br3- mIgG2a) over the course of the 7-day experiment as a positive control. The nonlinearity of exposure relative to dose between 100 and 200 mg/kg is a result of saturation of clearance mechanisms. The pharmacology of NIK SMI1 is examined in SD rat, CD-1 mouse, beagle, and cynomologous monkey with 20, 32, 18, and 7.8 mL/kg per min, respectively. Volume of distribution (Vd, L/kg) is 1.35, 1.58, 0.778, and 1.39, respectively[1].

Reference

[1]. Blaquiere N, et al. Scaffold-Hopping Approach To Discover Potent, Selective, and Efficacious Inhibitors of NF-κB Inducing Kinase. J Med Chem. 2018 Aug 9;61(15):6801-6813.
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