| Identification | Back Directory | [Name]
NIK SMI1 | [CAS]
1660114-31-7 | [Synonyms]
NIK SMI1
NIK inhibitor 4f(NIK SMI1)
(R)-6-(3-((3-Hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)phenyl)-4-methoxypicolinamide
2-Pyridinecarboxamide, 6-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxo-3-pyrrolidinyl]ethynyl]phenyl]-4-methoxy- | [Molecular Formula]
C20H19N3O4 | [MDL Number]
MFCD31715434 | [MOL File]
1660114-31-7.mol | [Molecular Weight]
365.38 |
| Chemical Properties | Back Directory | [Boiling point ]
626.7±55.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (273.69 mM) | [form ]
Solid | [pka]
11.14±0.20(Predicted) | [color ]
Off-white to pink | [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]
NC(C1=NC(C2=CC(C#C[C@]3(C(N(CC3)C)=O)O)=CC=C2)=CC(OC)=C1)=O |
| Hazard Information | Back Directory | [Uses]
NIK SMI1 is a highly potent and selective NF-κB-inducing kinase (NIK) inhibitor. | [Biological Activity]
NIK SMI1 is an orally activeATP site-targetingpotent and selective NF-KB-inducing kinase inhibitor (h/m NIK IC50 = 230/395 pM; hKHS1/hPKD1/hLRRK2 = 49.6/75.2/247.8 nM) th at selectively disrupts noncanonical NF-KB signaling (anti-LTβR-induced p52 nuclear translocation IC50 = 70 nM; TNFα-induced p65 RelA nuclear translocation IC50 >2 μM). SMI1 inhibits BAFF receptor- and CD40-mediated singling in cultures (human and murine B-cells) and shows in vivo efficacy in the NZB/W F1 murine experimental lupus model (6-400 mg/kg/dayb.i.d. p.o.). | [in vivo]
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]. | [storage]
Store at -20°C |
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