NF 157

NF157 is a highly selective nanomolar P2Y11 antagonist with a pKi of 7.35. The IC50s are 463 nM, 1811 µM, 170 µM for P2Y11 (Ki=44.3 nM), P2Y1 (Ki=187 µM), P2Y2 (Ki=28.9 µM), respectively[1]. NF157, significantly reduces expression of metalloproteinase (MMP)-3, MMP-13, can be used in the treatment of osteoarthritis (OA)[2].

Signaling Pathways >> GPCR/G Protein >> P2Y Receptor

Research Areas >> Inflammation/Immunology

pKi: 7.35 (P2Y11)[1] IC50: 463 nM (P2Y11), 1811 µM (P2Y1), 170 µM (P2Y2)[1] Ki: 44.3 nM (P2Y11), 187 µM (P2Y1), 28.9 µM (P2Y2)[1]

NF157 displays selectivity for P2Y11 over P2Y1 (>650-fold), P2Y2 (>650-fold), P2X2 (3-fold), P2X3 (8-fold), P2X4 (>22-fold), and P2X7 (>67-fold) but no selectivity over P2X1[1]. NF157 (30 and 60 µM; 24 hours) causes a significant reduction in degradation of type II collagen in a dose-dependent manner. 60 µM NF157 nearly completely rescues type II collagen from degradation induced by TNF-α (10 ng/mL)[2]. NF157 (30 and 60 µM; 24 hours) almost fully restores nuclear translocation of p65 triggered by TNF-α (10 ng/mL) and significantly reduces the luciferase activity of NF-κB[2]. Western Blot Analysis[2] Cell Line: SW1353 cells Concentration: 30 and 60 µM Incubation Time: 24 hours Result: Ameliorated TNF-α-induced degradation of type II collagen. Western Blot Analysis[2] Cell Line: SW1353 cells Concentration: 30 and 60 µM Incubation Time: 24 hours Result: Reduced TNF-α-induced activation of NF-κB.

[1]. Ullmann H, et al. Synthesis and structure-activity relationships of suramin-derived P2Y11 receptor antagonists with nanomolar potency. J Med Chem. 2005 Nov 3;48(22):7040-8.

[2]. Wang D, et al. Inhibition of P2Y11R ameliorated TNF-α-induced degradation of extracellular matrix in human chondrocytic SW1353 cells. Am J Transl Res. 2019 Apr 15;11(4):2108-2116.