Arginase Inhibitors

¹Buga GM, Singh R, Pervin S, Rogers NE, Schmitz DA, Jenkinson CP, Cederbaum SD, Ignarro LJ. Arginase activity in endothelial cells: inhibition by NG-hydroxy-L-arginine during high-output NO production. Am J Physiol 1996;271:H1988.

²Boucher JL, Moali C, Tenu JP. Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization. Cell Mol Life Sci 1999;55:1015 REVIEW .

³Tenu JP, Lepoivre M, Moali C, Brollo M, Mansuy D, Boucher JL. Effects of the new arginase inhibitor N(omega)-hydroxy-nor-L-arginine on NO synthase activity in murine macrophages. Nitric Oxide 1999;3:427.

⁴Colleluori DM, Ash DE. Classical and slow-binding inhibitors of human type II arginase. Biochemistry 2001;40:9356.

⁵Hein TW, Zhang C, Wang W, Chang CI, Thengchaisri N, Kuo L. Ischemia-reperfusion selectively impairs nitric oxide-mediated dilation in coronary arterioles: counteracting role of arginase. FASEB J 2003;17:2328.

⁶Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003;108:2000.

⁷Masuda H, Yano M, Sakai Y, Kihara K, Yamauchi Y, Azuma H. Modulation of intrinsic cavernous tone and nitric oxide production by arginase in rabbit corpus cavernosum. J Urol 2004;171:490.

⁸Zhang C, Hein TW, Wang W, Miller MW, Fossum TW, McDonald MM, Humphrey JD, Kuo L. Upregulation of Vascular Arginase in Hypertension Decreases Nitric Oxide-Mediated Dilation of Coronary Arterioles Hypertension 2004;44:935.

BEC

[(S)-(2-Boronoethyl)-L-cysteine]

Potency: Ki= 313 nM (for human recombinant type II) ¹

Membrane permeability: Y / Solubility: H₂O / MW: 229.5 (hydrochloride)

Comments: Boronic acid-based arginine analog. Competitive inhibitor. Slow-binding competitive transition state inhibitor of arginases I and II; it does not inhibit NOS¹.

¹Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003;108:2000.

CAUTION: -

ABH

[2(S)-amino-6-boronohexanoic acid]

Potency: IC₅₀= 0.05-0.44 µM; Ki= 0.018-0.19 µM ¹

Membrane permeability: Y / Solubility: H₂O / MW: 229.5 (hydrochloride)

Comments: Boronic acid-based arginine analog. Competitive inhibitor¹.

¹Baggio R, Emig FA, Christianson DW, Ash DE, Chakder S, Rattan S. Biochemical and functional profile of a newly developed potent and isozyme-selective arginase inhibitor. J Pharmacol Exp Ther 1999;290:1409.

CAUTION: -

N^G-Hydroxy-L-arginine

[NOHA; L-HO-Arg]

Potency: : Ki= 150 µM¹.

Membrane permeability: Y / Solubility: H₂O / MW: 250.3 (monoacetate salt)

Comments: Intermediate in the biosynthesis of NO¹. See references 2-5 for additional information.

¹Inhibitor SourceBook, Calbiochem, Merck Biosciences.

²Boucher JL, Custot J, Vadon S, Delaforge M, Lepoivre M, Tenu JP, Yapo A, Mansuy D. N(omega)-hydroxyl-L-arginine, an intermediate in the L-arginine to nitric oxide pathway, is a strong inhibitor of liver and macrophage arginase. Biochem Biophys Res Commun 1994;203:1614.

³Daghigh F, Fukuto JM, Ash DE. Inhibition of rat liver arginase by an intermediate in NO biosynthesis, N^G-hydroxy-L-arginine: implications for the regulation of nitric oxide biosynthesis by arginase. Biochem Biophys Res Commun 1994;202:174.

⁴Hecker M, Nematollahi H, Hey C, Busse R, Racke K. Inhibition of arginase by NG-hydroxy-L-arginine in alveolar macrophages: implications for the utilization of L-arginine for nitric oxide synthesis. FEBS Lett 1995;359:251.

⁵Buga GM, Singh R, Pervin S, Rogers NE, Schmitz DA, Jenkinson CP, Cederbaum SD, Ignarro LJ. Arginase activity in endothelial cells: inhibition by NG-hydroxy-L-arginine during high-output NO production. Am J Physiol 1996;271:H1988.

CAUTION: NOHA oxidation by cytochrome P450 results in NO.

N^omega-Hydroxy-nor-L-arginine

[nor-NOHA; L-2-Amino-(4-(2'-hydroxyguanidino)butyric acid]

Potency: IC₅₀= 2-50 µM¹.

Membrane permeability: - / Solubility: H₂O / MW: 296.3 (diacetate salt)

Comments: It is not substrate or inhibitor of NOS¹. See reference 2 for additional information.

¹Alexis Biochemicals.

²Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003;108:2000.

CAUTION: -

¹Tenu JP, Lepoivre M, Moali C, Brollo M, Mansuy D, Boucher JL. Effects of the new arginase inhibitor N(omega)-hydroxy-nor-L-arginine on NO synthase activity in murine macrophages. Nitric Oxide 1999;3:427.

DFMO

[DL-alfa-Difluoromethylornithine]

Potency: -

Membrane permeability: - / Solubility: - / MW: -

Comments: Commonly used as ornithine decarboxylase (ODC) inhibitor. ODC is the rate-limiting enzyme in polyamine biosynthesis¹.

¹Alexis Biochemicals.

CAUTION: -