Alvelestat

• CAT Number: I005079
• CAS Number: 848141-11-7
• Molecular Formula: C25H22F3N5O4S
• Molecular Weight: 545.53
• Purity: ≥95%
• Synonyms: 6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-N-((5-(methylsulfonyl)pyridin-2-yl)methyl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide
• Target: Elastase
• Solubility: DMSO: ≥ 33 mg/mL
• Storage: Store at -20°C
• IC50: 7.9 ± 0.12 (pIC50, Human NE); 4.9 nM (Ki value, Human NE) [1]
• InChI: InChI=1S/C25H22F3N5O4S/c1-15-20(22-9-10-31-32(22)2)12-21(23(34)30-13-17-7-8-19(14-29-17)38(3,36)37)24(35)33(15)18-6-4-5-16(11-18)25(26,27)28/h4-12,14H,13H2,1-3H3,(H,30,34)
• InChIKey: QNQZWEGMKJBHEM-UHFFFAOYSA-N
• SMILES: O=C(C1=CC(C2=CC=NN2C)=C(C)N(C3=CC=CC(C(F)(F)F)=C3)C1=O)NCC4=NC=C(S(=O)(C)=O)C=C4

Alvelestat (cas 848141-11-7) is a novel, oral inhibitor of neutrophil elastase (NE) with the pIC50 of 7.9 for Human NE.
IC50 Value: 7.9 ± 0.12 (pIC50, Human NE); 4.9 nM (Ki value, Human NE) 
Alvelestat had a high binding affinity for human NE (KD = 9.5 nM) and potently inhibited NE activity. The calculated pIC50 (IC50) and Ki values for Alvelestat for human NE were 7.9 (12 nM) and 4.9 nM, respectively. In contrast to earlier NE inhibitors, the interaction between Alvelestat and NE was rapidly reversible. AZD9668 was also highly selective for NE over other neutrophil-derived serine proteases. In cell-based assays, AZD9668 inhibited plasma NE activity in zymosan-stimulated whole blood. In isolated human polymorphonuclear cells, AZD9668 inhibited NE activity on the surface of stimulated cells and in the supernatant of primed, stimulated cells.AZD9668 showed good crossover potency to NE from other species.

Reference

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