L-NIL hydrochloride

L-NIL hydrochloride is an inducible NO synthase inhibitor, with an IC50 of 3.3 μM for miNOS[1][2][3].

Signaling Pathways >> Immunology/Inflammation >> NO Synthase

Research Areas >> Inflammation/Immunology

IC50: 3.3 μM (mouse inducible NO synthase), 92 μM (rat brain constitutive NO synthase)[1].

L-NIL produces a concentration-dependent inhibition of both the mouse inducible NOS (miNOS) and the rat brain constitutive NOS (rcNOS) and is considerably more potent for miNOS. The IC50 values for L-NIL with miNOS and rcNOS are 3.3 and 92 pM, respectively, indicating that L-NIL is 28-fold more selective for miNOS. In addition, L-NIL has approximately 6-fold greater potency for miNOS than either L-NMA or L-NNA[3].

L-NIL (10 and 30 mg/kg, IP) prevents the inflammation, oxidative stress and autophagy induced by renal IR in mice[1]. Animal Model: Adult male Balb/c (20-25 g)[1]. Dosage: 10 and 30 mg/kg. Administration: Intraperitoneally at the end of CLP and at 6 h after sepsis induction. Result: Led to a negligible increase in plasma NGAL compared to sham mice. Led to a significant decrease in both TLR4 and IL1βprotein contents and clusterin transcript. Showed an increase in NFAT5 mRNA levels, as compared with mice treated with vehicle. Promoted a decrease in AR protein expression, as compared with animals treated with vehicle.

[1]. Consuelo Pasten, et al. l-NIL prevents the ischemia and reperfusion injury involving TLR-4, GST, clusterin, and NFAT-5 in mice. Am J Physiol Renal Physiol. 2019 Apr 1;316(4):F624-F634.

[2]. Sharon Angela Tanuseputero, et al. Intravenous Arginine Administration Downregulates NLRP3 Inflammasome Activity and Attenuates Acute Kidney Injury in Mice with Polymicrobial Sepsis. Mediators Inflamm. 2020 May 11;2020:3201635.

[3]. Moore WM, et al. L-N6-(1-iminoethyl)lysine: a selective inhibitor of inducible nitric oxide synthase. J Med Chem. 1994 Nov 11;37(23):3886-8.